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Sample records for current pharmacological approaches

  1. Pharmacological chaperone approaches for rescuing GPCR mutants: Current state, challenges, and screening strategies.

    Science.gov (United States)

    Beerepoot, Pieter; Nazari, Reza; Salahpour, Ali

    2017-03-01

    A substantial number of G-protein coupled receptors (GPCRs) genetic disorders are due to mutations that cause misfolding or dysfunction of the receptor product. Pharmacological chaperoning approaches can rescue such mutant receptors by stabilizing protein conformations that behave similar to the wild type protein. For example, this can be achieved by improving folding efficiency and/or interaction with chaperone proteins. Although efficacy of pharmacological chaperones has been demonstrated in vitro for a variety of GPCRs, translation to clinical use has been limited. In this paper we discuss the history of pharmacological chaperones of GPCR's and other membrane proteins, the challenges in translation to the clinic, and the use of different assays for pharmacological chaperone discovery.

  2. Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations

    Directory of Open Access Journals (Sweden)

    Gardiner KJ

    2014-12-01

    Full Text Available Katheleen J Gardiner Linda Crnic Institute for Down Syndrome, Department of Pediatrics, Department of Biochemistry and Molecular Genetics, Human Medical Genetics and Genomics Program, Neuroscience Program, University of Colorado School of Medicine, Aurora, CO, USA Abstract: Down syndrome (DS, also known as trisomy 21, is the most common genetic cause of intellectual disability (ID. Although ID can be mild, the average intelligence quotient is in the range of 40–50. All individuals with DS will also develop the neuropathology of Alzheimer’s disease (AD by the age of 30–40 years, and approximately half will display an AD-like dementia by the age of 60 years. DS is caused by an extra copy of the long arm of human chromosome 21 (Hsa21 and the consequent elevated levels of expression, due to dosage, of trisomic genes. Despite a worldwide incidence of one in 700–1,000 live births, there are currently no pharmacological treatments available for ID or AD in DS. However, over the last several years, very promising results have been obtained with a mouse model of DS, the Ts65Dn. A diverse array of drugs has been shown to rescue, or partially rescue, DS-relevant deficits in learning and memory and abnormalities in cellular and electrophysiological features seen in the Ts65Dn. These results suggest that some level of amelioration or prevention of cognitive deficits in people with DS may be possible. Here, we review information from the preclinical evaluations in the Ts65Dn, how drugs were selected, how efficacy was judged, and how outcomes differ, or not, among studies. We also summarize the current state of human clinical trials for ID and AD in DS. Lastly, we describe the genetic limitations of the Ts65Dn as a model of DS, and in the preclinical testing of pharmacotherapeutics, and suggest additional targets to be considered for potential pharmacotherapies. Keywords: Ts65Dn, pharmacotherapy, clinical trials, Hsa21

  3. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  4. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Michael Kreuter

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid deterioration. In the last decade, improved understanding of disease mechanisms along with a more precise disease definition has allowed the design and completion of a number of high-quality clinical trials. Yet, until recently, IPF was essentially an untreatable disease. Finally, pirfenidone and nintedanib, two compounds with antifibrotic properties, have consistently proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough for patients and physicians alike, but there is still a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of comorbidities/complications and physical debility and timely referral for palliative care or, in a small number of highly selected patients, lung transplantation, remains essential. Several agents with high potential are currently being tested and many more are ready to be evaluated in clinical trials.

  5. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

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

  6. Quantitative systems pharmacology: a promising approach for translational pharmacology.

    Science.gov (United States)

    Gadkar, K; Kirouac, D; Parrott, N; Ramanujan, S

    Biopharmaceutical companies have increasingly been exploring Quantitative Systems Pharmacology (QSP) as a potential avenue to address current challenges in drug development. In this paper, we discuss the application of QSP modeling approaches to address challenges in the translational of preclinical findings to the clinic, a high risk area of drug development. Three cases have been highlighted with QSP models utilized to inform different questions in translational pharmacology. In the first, a mechanism based asthma model is used to evaluate efficacy and inform biomarker strategy for a novel bispecific antibody. In the second case study, a mitogen-activated protein kinase (MAPK) pathway signaling model is used to make translational predictions on clinical response and evaluate novel combination therapies. In the third case study, a physiologically based pharmacokinetic (PBPK) model it used to guide administration of oseltamivir in pediatric patients.

  7. 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.

  8. 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...

  9. Pharmacological approach to acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ulrich Christian Bang; Synne Semb; Camilla Nφjgaard; Flemming Bendtsen

    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) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi.Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-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 against tumor necrosis factor-alpha (TNF-α)have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics betalactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.

  10. 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.

  11. New approaches to pharmacological treatment of osteoporosis.

    Science.gov (United States)

    Akesson, Kristina

    2003-01-01

    Osteoporosis has been recognized as a major public health problem for less than two decades. The increasing incidence of fragility fractures, such as vertebral, hip, and wrist fractures, first became apparent from epidemiological studies in the early and mid-1980s, when effective treatment was virtually unavailable. Pharmacological therapies that effectively reduce the number of fractures by improving bone mass are now available widely in countries around the world. Most current agents inhibit bone loss by reducing bone resorption, but emerging therapies may increase bone mass by directly promoting bone formation--as is the case with parathyroid hormone. Current treatment alternatives include bisphosphonates, calcitonin, and selective estrogen receptor modulators, but sufficient calcium and vitamin D are a prerequisite. The availability of evidence-based data that show reductions in the incidence of fractures of 30-50% during treatment has been a major step forward in the pharmacological prevention of fractures. With all agents, fracture reduction is most pronounced for vertebral fracture in high-risk individuals; alendronate and risedronate also may protect against hip fracture in the elderly. New approaches to pharmacological treatment will include further development of existing drugs, especially with regard to tolerance and frequency of dosing. New avenues for targeting the condition will emerge as our knowledge of the regulatory mechanisms of bone remodelling increases, although issues of tissue specificity may be difficult to solve. In the long term, information gained through knowledge of bone genetics may be used to adapt pharmacological treatments more precisely to each individual.

  12. 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.

  13. [Negative symptoms in schizophrenia: new pharmacological approaches].

    Science.gov (United States)

    Lodovighi, M-A; Palomba, A; Belzeaux, R; Adida, M; Azorin, J-M

    2015-12-01

    The management of negative symptoms appears to be a major challenge because of functional disability induced by these symptoms and their relative resistance to treatments currently on the market. The aim of this article is to review new approaches that may enable optimal management of these symptoms. First, we describe the methodological difficulties that hindered the development and evaluation of specific treatment, and objectives currently defined to enable the development of new pharmacological approaches. Then we present the monotherapy and adjuvant therapies that have been assessed, including first and second generation antipsychotics, psychostimulants, antidepressants, cholinergic and glutamatergic agents, the oxytocin, hormones and more invasive therapies such as transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Other molecules are under development and evaluation such alpha-7 nicotinic receptor agonists.

  14. Vascular dementia: Pharmacological treatment approaches and perspectives

    Directory of Open Access Journals (Sweden)

    Andrius Baskys

    2007-10-01

    Full Text Available Andrius Baskys1,3, Anthony C Hou21Department of Psychiatry and Human Behavior; 2Program in Geriatrics, University of California at Irvine, Irvine, California; 3Memory Disorders Program, VA Health Care System Long Beach, Long Beach, California, USAAbstract: Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDPcholine, folic acid, as well as such nonpharmacological approaches as validation therapy.Keywords: vascular dementia, excitotoxicity, treatment, NMDA, memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid

  15. Current status and future directions of pharmacological therapy for acromegaly.

    Science.gov (United States)

    Mercado, Moisés; Espinosa, Etual; Ramírez, Claudia

    2016-09-01

    Acromegaly is a chronic systemic disorder caused in the vast majority of cases by a GH-secreting pituitary adenoma and resulting in significant morbidity and mortality if left untreated. The treatment of choice is the trans-sphenoidal resection of the adenoma, and although 80% of patients with microadenomas or confined macroadenomas achieve biochemical remission, the surgical success rate for patients harboring tumors with extrasellar extension is below 50%. Thus, a considerable proportion of patients will require some form of adjuvant treatment. Acromegaly can be approached pharmacologically by inhibiting GH secretion by the tumor (somatostatin analogues, dopamine agonists) or by antagonizing GH actions at its target tissues (GH receptor antagonists). The primary pharmacological treatment of acromegaly is increasingly gaining acceptance by both physicians and patients. The decision to use primary pharmacological treatment has to take into account the clinical characteristics of the patient (presence of comorbidities that significantly increase the surgical risk) and the biological nature of the adenoma (tumor size and location), as well as other aspects such as the availability of a pituitary surgeon and the cost of medications. This review provides a critical summary and update of the pharmacological treatment of acromegaly focusing both, on well-established agents and strategies as well as on novel compounds that are currently being developed.

  16. [Clinical pharmacology of current antiplatelet drugs].

    Science.gov (United States)

    Trenk, D; Nührenberg, T; Stratz, C; Valina, C M; Hochholzer, W

    2014-11-01

    Dual antiplatelet therapy with low-dose acetylsalicylic acid (ASA) and an inhibitor of the P2Y12 adenosine diphosphate (ADP) receptor is the standard treatment for patients presenting with acute coronary syndrome (ACS) or undergoing elective coronary interventions according to the current guidelines published by the European Society of Cardiology (ESC). New generation P2Y12 inhibitors, such as prasugrel and ticagrelor exert stronger and more consistent inhibition of the P2Y12 receptor. In clinical studies enrolling patients with ACS these drugs decreased the incidence of ischemic events compared to the standard therapy with clopidogrel and ASA; however, this beneficial effect was associated with an increase in bleeding events. Alternative therapeutic approaches via addition of drugs with different modes of action showed an overall reduction of ischemic events but also failed to uncouple this beneficial effect from an increased bleeding risk.

  17. 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 compou

  18. 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

  19. 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.

  20. Current Pharmacological Management of Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    Yao-Kuang Wang

    2013-01-01

    Full Text Available Gastroesophageal reflux disease (GERD, a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.

  1. [Non-pharmacologic approach in severe dementia].

    Science.gov (United States)

    Pancrazi, Marie-Pierre; Métais, Patrick

    2005-03-01

    Care for patients with Alzheimer's disease, particularly with severe dementia, requires a global therapeutic strategy integrating pharmacological approach into the environmental dimensions, psychotherapeutics and rehabilitation. The objective is to maintain autonomy as long as possible but also to improve the quality of life by reducing the psychological suffering of patients and families. In severe dementia, behavioral techniques and organization of the environment are possible at home but, actually, most of the patients are institutionalized. Structures having a specific project of life, of care and specific architectural design should be preferred. Education and support for caregivers as well as training of the nursing staff are essential to develop better attitudes toward the patient, improve communication and optimize the quality of life. In spite of the low level of evidence in the evaluation of these strategies on account of the lack of adapted indicators and rarity of specific research, widely spread techniques can confer special purport to this difficult stage for the patients and their family.

  2. 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.

  3. Therapies for Parkinson's diseases: alternatives to current pharmacological interventions.

    Science.gov (United States)

    Li, Song; Dong, Jie; Cheng, Cheng; Le, Weidong

    2016-11-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder caused by the selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although PD has been heavily researched, the precise etiology and pathogenesis for PD are still inconclusive. Consequently, current pharmacological treatments for PD are largely symptomatic rather than preventive and there is still no cure for this disease nowadays. Moreover, nonmotor symptoms caused by intrinsic PD pathology or side effects induced by currently used pharmacological interventions are gaining increasing attention and urgently need to be treated due to their influence on quality of life. As ancient traditional healing systems, Tai Chi, Yoga, acupuncture and natural products have long been considered as complementary or alternative therapeutic options for PD. Recently, several newly developed non-pharmacological therapeutic strategies, including deep brain stimulation, repetitive transcranial magnetic stimulation, near-infrared light, gene therapy and cell replacement therapy, have also been suggested to give benefits to relieve parkinsonian symptoms. This review will summarize and update the therapeutic potential and the most recent research progresses of these traditional and modern therapeutic options and highlight their clinical meaning for the therapy of not only PD but also other neurodegenerative diseases.

  4. Current status of NADPH oxidase research in cardiovascular pharmacology

    Directory of Open Access Journals (Sweden)

    Rodiño-Janeiro BK

    2013-07-01

    Full Text Available Bruno K Rodiño-Janeiro,1,2 Beatriz Paradela-Dobarro,1 María Isabel Castiñeiras-Landeira,1 Sergio Raposeiras-Roubín,1,3 José R González-Juanatey,1,3,4 Ezequiel Álvarez1,4 1Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 2European Molecular Biology Laboratory, Grenoble, France; 3Cardiology Department, University Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 4Medicine Department, University of Santiago de Compostela, Santiago de Compostela, Spain Abstract: The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility

  5. Bruxism and Current Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Selin Eren

    2016-06-01

    Full Text Available Among the mastication system disorders bruxism is a parafunctional behavior that comes from psychophysiological origin. Epidemiologic studies have reported great variability of bruxism prevalence. The factors that could cause bruxism is highly controversial. There are different opinions on this issue. The etiologic factors of bruxism include stress, malnutrition, allergic and endocrinologic diseases, central nervous system disorders, genetic factors, medicines, malocclusion, and wrong dental treatment. The aim of treatment of bruxism is to prevent damage that may occur on teeth and in the temporomandibular joint and to eliminate pain. Dental treatment, physical therapy, pharmacological treatment and behavioral and cognitive therapy can be considered for this purpose of treatment. This review summarizes the etiologic factors, epidemiology, diagnosis, and current treatment approaches of patient with bruxism. [Archives Medical Review Journal 2016; 25(2.000: 241-258

  6. Pharmacological Approach for Treatment of Retinopathy of Prematurity

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    İmren Akkoyun

    2012-12-01

    Full Text Available Current standard of screening examination for retinopathy of prematurity (ROP is determined in international guidelines. The criteria for classification and therapy are also determined in international guidelines, and currently, retinal laser fotocoagulation of peripheral avascular retinal area is gold standard (ETROP, Early Treatment for Retinopathy of Prematurity Cooperative Group for proliferative ROP. Vitreoretinal surgery will be used in cases with retinal detachment. In case series after off-label injection of anti-VEGF (vascular endothelial growth factor agent bevacizumab and in the first report of BEAT-ROP study in proliferative ROP the results are promising. Furthermore, beside the intravitreal anti-VEGF therapy, systemic therapy with mediators like IGF-1 (insulin-like growth factor and/or ω3-fatty acids outlines pharmacological approach to treatment of ROP. The results of well-designed clinical trials of intravitreal anti-VEGF therapy and pharmacological systemic therapy with the above-mentioned mediators for ROP are needed in order to provide information as to the balance of risk versus benefit, as well as practical guidance regarding optimal treatment parameters and follow-up.(Turk J Ophthalmol 2012; 42: 466-73

  7. Pharmacologic approaches to the treatment of cocaine dependence.

    OpenAIRE

    Taylor, W. A.; Gold, M. S.

    1990-01-01

    When pharmacologic agents are considered in the treatment of cocaine addiction, the objective of such treatment--sustained abstinence--must be considered. Medication and medical approaches have been disappointing in the treatment of cocaine overdose. The central neurobiologic mechanism(s) involved in cocaine toxicity are poorly understood. Without a cocaine antagonist, pharmacologic approaches have been less than promising in preventing relapse. Various psychoactive medications have been trie...

  8. The potential of translational bioinformatics approaches for pharmacology research.

    Science.gov (United States)

    Li, Lang

    2015-10-01

    The field of bioinformatics has allowed the interpretation of massive amounts of biological data, ushering in the era of 'omics' to biomedical research. Its potential impact on pharmacology research is enormous and it has shown some emerging successes. A full realization of this potential, however, requires standardized data annotation for large health record databases and molecular data resources. Improved standardization will further stimulate the development of system pharmacology models, using translational bioinformatics methods. This new translational bioinformatics paradigm is highly complementary to current pharmacological research fields, such as personalized medicine, pharmacoepidemiology and drug discovery. In this review, I illustrate the application of transformational bioinformatics to research in numerous pharmacology subdisciplines. © 2015 The British Pharmacological Society.

  9. 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.

  10. 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.

  11. Current developments in pharmacological therapeutics for chronic constipation

    Directory of Open Access Journals (Sweden)

    Chunhuan Jiang

    2015-07-01

    Full Text Available Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.

  12. Available therapies and current management of fibromyalgia: focusing on pharmacological agents.

    Science.gov (United States)

    Han, C; Lee, S-J; Lee, S-Y; Seo, H-J; Wang, S-M; Park, M-H; Patkar, A A; Koh, J; Masand, P S; Pae, C-U

    2011-07-01

    Fibromyalgia (FM) is a chronic medical condition characterized by physical, psychiatric and psychological symptoms. Widespread pain, fatigue, sleep disturbances, heightened sensitivity, morning stiffness, decreased volition, depressed mood and a history of early abuse are frequently reported by patients with FM. Treatment of fibromyalgia is multidisciplinary, with an emphasis on active patient participation, medications, cognitive-behavioral therapy and physical modalities. No single medication has yet been found to sufficiently control all the symptoms of FM; currently available medication classes include antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, analgesics, hypnotic agents and anticonvulsants. Hence, treatment for patients with FM, including pharmacological and non-pharmacological approaches, should be individualized based on each patient's clinical history, target symptoms and functional impairments. Although nonpharmacological modalities are also frequently used, recent research has focused on identifying more effective pharmacological treatments, particularly antidepressants and anticonvulsants. Furthermore, several new pharmacological agents have been now officially approved for the treatment of patients with FM. Thus, the purpose of this review is to help healthcare professionals make informed decisions about the appropriate use of a number of pharmacological treatments for patients with FM.

  13. Systems pharmacology modeling: an approach to improving drug safety.

    Science.gov (United States)

    Bai, Jane P F; Fontana, Robert J; Price, Nathan D; Sangar, Vineet

    2014-01-01

    Advances in systems biology in conjunction with the expansion in knowledge of drug effects and diseases present an unprecedented opportunity to extend traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct systems pharmacology modeling. Many drugs that cause liver injury and myopathies have been studied extensively. Mitochondrion-centric systems pharmacology modeling is important since drug toxicity across a large number of pharmacological classes converges to mitochondrial injury and death. Approaches to systems pharmacology modeling of drug effects need to consider drug exposure, organelle and cellular phenotypes across all key cell types of human organs, organ-specific clinical biomarkers/phenotypes, gene-drug interaction and immune responses. Systems modeling approaches, that leverage the knowledge base constructed from curating a selected list of drugs across a wide range of pharmacological classes, will provide a critically needed blueprint for making informed decisions to reduce the rate of attrition for drugs in development and increase the number of drugs with an acceptable benefit/risk ratio.

  14. Pharmacological versus non-pharmacological approaches to managing challenging behaviours for people with dementia.

    Science.gov (United States)

    Jones, Tony; Hungerford, Catherine; Cleary, Michelle

    2014-02-01

    When people with dementia demonstrate challenging behavioural and psychological symptoms of dementia, the levels of stress experienced by their carers increases. Furthermore, there is an increased likelihood that the person will be prematurely admitted to a residential care facility. The adverse side-effects that have been associated with the use of antipsychotic medications in older people with dementia have given rise to a renewed emphasis on the use of non-pharmacological approaches to manage challenging behaviours. This article describes the approaches taken by the multi-disciplinary team of a Dementia Behaviour Management Advisory Service in Australia to support people with dementia who have challenging behaviours by using non-pharmacological interventions.

  15. A pharmacological approach to first aid treatment for snakebite.

    Science.gov (United States)

    Saul, Megan E; Thomas, Paul A; Dosen, Peter J; Isbister, Geoffrey K; O'Leary, Margaret A; Whyte, Ian M; McFadden, Sally A; van Helden, Dirk F

    2011-06-26

    Snake venom toxins first transit the lymphatic system before entering the bloodstream. Ointment containing a nitric oxide donor, which impedes the intrinsic lymphatic pump, prolonged lymph transit time in rats and humans and also increased rat survival time after injection of venom. This pharmacological approach should give snakebite victims more time to obtain medical care and antivenom treatment.

  16. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    Science.gov (United States)

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  17. [Non-pharmacological and pharmacological treatment of arterial hypertension: current situation].

    Science.gov (United States)

    Hoyer, J

    2012-11-01

    A permanent and successful treatment of high blood pressure is based on a combination of non-pharmacological treatment measures and pharmacological therapy. The most proven non-pharmacological measures are physical and sports activities, weight reduction, dietary adaption and reduction of salt intake as well as nicotine abstinence and moderate alcohol consumption. A blood pressure reducing effect of evidence grade A was demonstrated for these 4 pillars of non-pharmacological therapy in studies. For pharmacological treatment five main substance groups are available: thiazide diuretics, ACE inhibitors, AT1 blockers, calcium channel blockers and beta blockers. A very good blood pressure reducing effect with an advantageous side effect profile has been proven for all substances. The initial high blood pressure therapy can be carried out with monotherapy but therapy with several antihypertensives is often necessary for the very varied combination of compounds which are available in a meaningful combination and dosage of effective ingredients. For the treatment of comorbid hypertensive patients recommendations are available for an individualized pharmacological treatment corresponding to the specific cardiovascular risk and comorbidity. High blood pressure therapy must be continuously carried out over many years. For permanent success of the therapy good compliance is indispensible which can be encouraged by integration in the therapy and should be regularly controlled.

  18. Pharmacological inhibition of FAAH activity in rodents: A promising pharmacological approach for psychological-cardiac comorbidity?

    Science.gov (United States)

    Carnevali, Luca; Rivara, Silvia; Nalivaiko, Eugene; Thayer, Julian F; Vacondio, Federica; Mor, Marco; Sgoifo, Andrea

    2017-03-01

    Numerous studies have documented a link between psychological disorders and cardiac disease. Yet, no systematic attempts have been made to develop pharmacological approaches for mood and anxiety disorders that could also be beneficial for cardiac health. The endocannabinoid system has been implicated in the regulation of stress, emotional behavior and cardiovascular function. General preclinical findings indicate that the endocannabinoid anandamide modulates physiological and behavioral stress responses and may also protect the heart from arrhythmias. Moreover, recent experimental studies suggest that pharmacological enhancement of anandamide signaling via inhibition of its degrading enzyme fatty acid amide hydrolase (FAAH) exerts anxiolytic- and antidepressive-like effects and improves cardiac autonomic function and the electrical stability of the myocardium in rodent models that reproduce aspects of human psychological/cardiac comorbidity. Here we summarize and discuss such experimental findings, which might guide future preclinical studies towards a systematic evaluation of the therapeutic potential of pharmacological approaches that target FAAH activity for the treatment of the comorbidity between psychological disorders and cardiac disease.

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

    Science.gov (United States)

    Ultsch, Alfred

    2016-01-01

    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. PMID:27069773

  20. Pharmacologically regulated induction of silent mutations (PRISM): combined pharmacological and genetic approaches for learning and memory.

    Science.gov (United States)

    Frankland, Paul W; Ohno, Masuo; Takahashi, Eiki; Chen, Adele R; Costa, Rui M; Kushner, Steven A; Silva, Alcino J

    2003-04-01

    Mouse transgenic and knock-out approaches have made fundamental contributions to our understanding of the molecular and cellular bases of learning and memory. These approaches have successfully identified a large number of molecules with either a central or modulatory role in learning and memory. However, there are limitations associated with first-generation mutant mice, which include, for example, the lack of temporal control over the mutation. Recent technical developments have started to address some of these shortcomings. Here, the authors review a newly developed inducible approach that takes advantage of synergistic interactions between subthreshold genetic and pharmacological manipulations. This approach is easily set up and can be used to study the functional interactions between molecules in signaling pathways.

  1. Pharmacological approaches to the management of binge eating disorder.

    Science.gov (United States)

    Brownley, Kimberly A; Peat, Christine M; La Via, Maria; Bulik, Cynthia M

    2015-01-01

    In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5 % in adult women, 2.0 % in adult men, and 1.6 % in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the

  2. Current state and prospect of pharmacological approaches to amphetamine-type stimulants dependence%苯丙胺类依赖的药物治疗现状和展望

    Institute of Scientific and Technical Information of China (English)

    崔巍; 沈雯雯; 周文华; 韩怡凡

    2012-01-01

    笨丙胺类药物是国内第二大成瘾性药物,苯丙胺类依赖是一个重要的公共健康问题,但至今尚未发现有效的治疗药物.本文首先介绍了苯丙胺类依赖形成的多巴胺和非多巴胺机制,并对多巴胺转运体抑制剂、多巴胺受体部分激动剂及拮抗剂、谷氨酸受体拮抗剂、乙酰胆碱酯酶抑制剂、γ-氧基丁酸受体激动剂、5-羟色胺转运体抑制剂以及阿片受体拮抗剂等已用于苯丙胺类依赖治疗实践的药物进行了系统综述,并展望了苯丙胺类依赖治疗药物的研究方向.%Amphetamine-type stimulants ( ATS) are the second most widely used addictive drugs in China. ATS dependence has become a serious public heath problem. Currently, there is no pharmacological treatment with established efficacy for inhibiting this addictive disorder. Changes of non-dopaminergic systems implicated in ATS dependence, such as GABAergic, cholinergic and glutamatergic systems, suggest that this addictive disorder be treated with drugs targeting either the dopaminergic system or non-dopaminergic system. This paper reviews pharmacological candidates, including the inhibitors of dopamine and serotonin transporters, the partial agonists of do-pamine receptors, the antagonists of glutamate receptor, and the inhibitors of acetylcholinesterase, which might be useful in the treatment of ATS dependence based on preclinical data. The prospect of novel anti-ATS dependence drugs being developed is also discussed.

  3. Pharmacological manipulation of brain glycogenolysis as a therapeutic approach to cerebral ischemia.

    Science.gov (United States)

    Xu, Li; Sun, Hongbin

    2010-10-01

    Brain ischemia resulting from multiple disease states including cardiac arrest, stroke and traumatic brain injury, is a leading cause of death and disability. Despite significant resources dedicated to developing pharmacological interventions, few effective therapeutic options are currently available. The basic consequence of cerebral ischemia, characterized by energy failure and subsequent brain metabolic abnormalities, enables the protective effects by pharmacological manipulation of brain metabolism. We present here the important roles of brain glycogen metabolism and propose inhibition of glycogenolysis as a therapeutic approach to cerebral ischemia.

  4. Approaches to the pharmacological treatment of obesity.

    Science.gov (United States)

    Salem, Victoria; Bloom, Stephen R

    2010-01-01

    Obesity is a global health crisis resulting in major morbidity and premature death. The need for safe and efficacious drug therapies is great, and presently unmet. The two drugs currently licensed in the USA for the long-term treatment of obesity, orlistat and sibutramine, provide only modest weight-loss benefits and are associated with high attrition rates owing to side effects. This review summarizes current concepts in the neuroendocrine control of energy homeostasis and major pharmacological treatments for obesity in the pipeline.

  5. Current pharmacological and phytochemical studies of the plant Alpinia galanga.

    Science.gov (United States)

    Kaushik, Dhirender; Yadav, Jyoti; Kaushik, Pawan; Sacher, Disha; Rani, Ruby

    2011-10-01

    Traditional medicine systems consist of large numbers of plants with medicinal and pharmacological importance and hence represent an invaluable reservoir of new bioactive molecules. Alpinia galanga (family Zingiberaceae) is commonly known as galangal and has been used for its emmenagogue, aphrodisiac, abortifacient, carminative, antipyretic and anti-inflammatory qualities and used in the treatment of various diseases such as bronchitis, heart diseases, chronic enteritis, renal calculus, diabetes, rheumatism and kidney disorders. It was reported to contain, among other components, essential oils, tannins, phenol, glycosides, monoterpenes and carbohydrates. In the last few years, new compounds such as gallic acid glycoside, galangoisoflavonoid,β-sitosterol, galangin, alpinin, zerumbone and kampferide have been isolated from various parts of A. galanga. Therefore, the present review is aimed to summarize the information regarding A. galanga concerning the new phytoconstituents and pharmacological uses that have appeared in recent years.

  6. 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

  7. Current knowledge and pharmacological profile of berberine: An update.

    Science.gov (United States)

    Kumar, Anil; Ekavali; Chopra, Kanwaljit; Mukherjee, Madhurima; Pottabathini, Raghavender; Dhull, Dinesh K

    2015-08-15

    Berberine, a benzylisoquinoline alkaloid, occurs as an active constituent in numerous medicinal plants and has an array of pharmacological properties. It has been used in Ayurvedic and Chinese medicine for its antimicrobial, antiprotozoal, antidiarrheal and antitrachoma activity. Moreover, several clinical and preclinical studies demonstrate ameliorative effect of berberine against several disorders including metabolic, neurological and cardiological problems. This review provides a summary regarding the pharmacokinetic and pharmacodynamic features of berberine, with a focus on the different mechanisms underlying its multispectrum activity. Studies regarding the safety profile, drug interactions and important clinical trials of berberine have also been included. Clinical trials with respect to neurological disorders need to be undertaken to exploit the beneficiary effects of berberine against serious disorders such as Alzheimer's and Parkinson's disease. Also, clinical studies to detect rare adverse effects of berberine need to be initiated to draw a complete safety profile of berberine and strengthen its applicability.

  8. A Network Pharmacology Approach to Uncover the Pharmacological Mechanism of XuanHuSuo Powder on Osteoarthritis

    Science.gov (United States)

    Zhang, Xinyue; Luo, Shilin; Zhang, Baixia; Duan, Xiaojie; Zhang, Zhiqian; Wang, Wenqi; Wang, Yun; Sun, Yikun

    2016-01-01

    As the most familiar type of arthritis and a chronic illness of the joints, Osteoarthritis (OA) affects a great number of people on the global scale. XuanHuSuo powder (XHSP), a conventional herbal formula from China, has been extensively applied in OA treatment. Nonetheless, its pharmacological mechanism has not been completely expounded. In this research, a network pharmacology approach has been chosen to study the pharmacological mechanism of XHSP on OA, and the pharmacology networks were established based on the relationship between four herbs found in XHSP, compound targets, and OA targets. The pathway enrichment analysis revealed that the significant bioprocess networks of XHSP on OA were regulation of inflammation, interleukin-1β (IL-1β) production and nitric oxide (NO) biosynthetic process, response to cytokine or estrogen stimuli, and antiapoptosis. These effects have not been reported previously. The comprehensive network pharmacology approach developed by our research has revealed, for the first time, a connection between four herbs found in XHSP, corresponding compound targets, and OA pathway systems that are conducive to expanding the clinical application of XHSP. The proposed network pharmacology approach could be a promising complementary method by which researchers might better evaluate multitarget or multicomponent drugs on a systematic level. PMID:27110264

  9. Current and prospective pharmacological targets in relation to antimigraine action

    NARCIS (Netherlands)

    S. Mehrotra (Suneet); S. Gupta (Sanjay); K.Y. Chan (Kayi); C.M. Villalón (Carlos); D. Centurion (David); P.R. Saxena (Pramod Ranjan); A. Maassen van den Brink (Antoinette)

    2008-01-01

    textabstractMigraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that h

  10. [An approach to the pharmacological treatment of autism].

    Science.gov (United States)

    Ruggieri, V L

    1996-11-01

    In the past decade, notable advances have been made with regard to understanding the clinical, biological and epidermological aspects of the basic disorders of development (TPD), particularly autism. Nevertheless, our knowledge of the neurobiological basis is still limited. This has impeded the development of drugs which correct the defect and cure the illness. Although there is no perfect drug, in recent years clinico-pharmacological research has made it possible to use drugs which have been very helpful in correcting the symptoms associated with these disorders. These drugs have permitted a better therapeutic approach and improved family and social integration of these children (in the family and in society). We will proceed to analyze some of the drugs shown to be useful for treatment of children with TPD.

  11. The current status and trend of clinical pharmacology in developing countries

    Science.gov (United States)

    2013-01-01

    Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of

  12. Pharmacological approaches to retinitis pigmentosa: A laboratory perspective.

    Science.gov (United States)

    Guadagni, Viviana; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

    2015-09-01

    Retinal photoreceptors are highly specialized and performing neurons. Their cellular architecture is exquisitely designed to host a high concentration of molecules involved in light capture, phototransduction, electric and chemical signaling, membrane and molecular turnover, light and dark adaption, network activities etc. Such high efficiency and molecular complexity require a great metabolic demand, altogether conferring to photoreceptors particular susceptibility to external and internal insults, whose occurrence usually precipitate into degeneration of these cells and blindness. In Retinitis Pigmentosa, an impressive number of mutations in genes expressed in the retina and coding for a large varieties of proteins leads to the progressive death of photoreceptors and blindness. Recent advances in molecular tools have greatly facilitated the identification of the underlying genetics and molecular bases of RP leading to the successful implementation of gene therapy for some types of mutations, with visual restoration in human patients. Yet, genetic heterogeneity of RP makes mutation-independent approaches highly desirable, although many obstacles pave the way to general strategies for treating this complex disease, which remains orphan. The review will focus on treatments for RP based on pharmacological tools, choosing, among the many ongoing studies, approaches which rely on strong experimental evidence or rationale. For perspective treatments, new concepts are foreseen to emerge from basic studies elucidating the pathways connecting the primary mutations to photoreceptor death, possibly revealing common molecular targets for drug intervention.

  13. [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.

  14. [Neurocognitive and pharmacological approach to specific learning disorders].

    Science.gov (United States)

    Etchepareborda, M C

    1999-02-01

    Specific learning disorders are distinguished from general development disorders since, in general, only a certain number of processing mechanisms are involved whilst the remainder are unaffected. The classification proposed by the DSM-IV takes a step towards clinical understanding and use of a common nomenclature. However, neuropsychological assessment is essential to understanding clinical subtypes. The neuro-cognitive approach, when taking into account the processing systems affected or involved, should include the strategies and principles of a cognitive-behavioural approach, accompanied by computerized cognitive training. Pharmacological treatment uses drugs with different modes of action depending on the specific neuropsychological characteristics of each type of disorder of nerve development. We discuss the clinical use of various drugs in view of investigations, present and past: methylphenidate for the dys-attentional subtype of ADHD; piracetam in developmental dyslexia of dysideatic type; citocolina in the infantile dysphasias of sensory input predominance, thiapride in dysfluencial and combined subtype of ADHD; pipamperona in behaviour disorders and the hyperactive-impulsive subtype of ADHD, with or without associated and selegilina in the dysattention subtype of ADHD and the dysgraphias of the subtype with predominance of calligraphy and spatial disorders.

  15. Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.

    Science.gov (United States)

    Rosenberg, Russell P

    2006-01-01

    Although insomnia is highly prevalent, sleep disturbances often go unrecognized and untreated. When insomnia is recognized, considerable emphasis has been placed on improving sleep onset; however, there is growing evidence that improving sleep maintenance is an equally important treatment goal. A MEDLINE literature search was performed using the search parameters "insomnia," "zolpidem," "zaleplon," "flurazepam," "estazolam," "quazepam," "triazolam," and "temazepam," as these agents are FDA-approved for the treatment of insomnia. Per reviewer comments, the search criteria was later expanded to include lorazepam. A literature search using the terms "trazodone" and "insomnia" was also performed, as this is the second-most commonly prescribed agent for treating insomnia. Sleep efficacy endpoints from randomized, placebo-controlled clinical trials in adult populations and key review articles published between 1975 and 2004 were included in this review. As only one randomized placebo-controlled trial evaluated trazodone use in primary insomnia, the trazodone search was expanded to include all clinical trials that evaluated trazodone use in insomnia. Relevant texts and other articles that evaluated side effect profiles of these agents were also included, one of which was published in January of 2005. In all publications, impact of treatment on sleep maintenance parameters (wake time after sleep onset, number of awakenings) and measures of next-day functioning were evaluated, in addition to sleep onset parameters (sleep latency, time to sleep onset/induction) and sleep duration data (total sleep time). Many of the currently available agents used to treat insomnia, including the antidepressant trazodone, the non-benzodiazepine hypnotics zolpidem and zaleplon, and some of the benzodiazepines, have not consistently demonstrated effectiveness in promoting sleep maintenance. Furthermore, the benzodiazepines with established sleep maintenance efficacy are associated with next

  16. Targets for Current Pharmacological Therapy in Cholesterol Gallstone Disease

    Science.gov (United States)

    Di Ciaula, Agostino; Wang, David Q.-H.; Wang, Helen H.; Bonfrate, Leonilde; Portincasa, Piero

    2010-01-01

    Summary Gallstone disease is a frequent condition throughout the world and cholesterol stones are the most frequent form in western countries. Current standard treatment of symptomatic gallstone subjects remains laparoscopic cholecystectomy. The selection of patients amenable for non-surgical, medical therapy is of key importance: a careful analysis should consider the natural history of the disease and the overall costs of therapy. Only patients with mild symptoms and small, uncalcified cholesterol gallstones in a functioning gallbladder with a patent cystic duct will be considered for oral litholysis by the hydrophilic ursodeoxycholic acid (UDCA) hopefully leading to cholesterol desaturation of bile and progressive stone dissolution. Recent studies have raised the possibility that cholesterol-lowering agents which inhibit hepatic cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis may offer, alone or in combination, additional medical therapeutic tools for treating cholesterol gallstones. Recent perspectives on medical treatment of cholesterol gallstone disease will be discussed in this chapter. PMID:20478485

  17. 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.

  18. 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.

  19. 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

  20. [The pedagogical approach to pharmacology in nurse training institutes].

    Science.gov (United States)

    Schweyer, Lucette

    2016-05-01

    Seen as daunting and stressful, pharmacology is often rejected by student nurses. This discipline requires and draws on multiple skills. When future nurses realise that their prescribing role goes beyond simple execution, they are able to appreciate the full scope of pharmacology.

  1. 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)

  2. Management of pain in multiple sclerosis: a pharmacological approach.

    Science.gov (United States)

    Solaro, Claudio; Uccelli, Michele Messmer

    2011-08-16

    About half of patients with multiple sclerosis (MS) report pain; treatment for pain alone accounts for nearly 30% of the total use of medications for the management of all MS-related symptoms. Patients with MS can experience more than one type of pain simultaneously and at any point during the disease course, even in newly or recently diagnosed cases. Pain in MS can be associated with other symptoms, including spasticity, fatigue and mood disorder. Pain sufferers experience disruption in daily life activities, work, mood, recreation and general enjoyment of life, and report low satisfaction with pain management. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. The majority of clinical evidence regarding treatment stems from small pilot and open-label studies; therefore, treatment of pain associated with MS is often based on anecdotal reports and clinicians' experience. The open-label design of the majority of studies, the unavailability of large samples and the difficulty of performing placebo-controlled studies because of ethical considerations result in insufficient evidence to support or refute the effectiveness of pain medications. This Review presents available data regarding pharmacological approaches for addressing pain in MS and highlights the shortcomings in pain management research.

  3. 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

  4. Anorexia-cachexia syndrome in pancreatic cancer: recent advances and new pharmacological approach.

    Science.gov (United States)

    Ronga, Ilaria; Gallucci, Fernando; Riccardi, Ferdinando; Uomo, Generoso

    2014-03-01

    About 80% of all pancreatic ductal adenocarcinoma patients suffer from a wasting syndrome referred to as the "cancer anorexia-cachexia syndrome" (CACS) characterized by abnormally low weight, weakness and loss of skeletal muscle mass with or without loss of body fat, which directly impacts overall survival, quality of life, and physical activity. The aim of this review was to examine recent findings about CACS' pathophysiology and to describe the current pharmacological approaches. In recent years many efforts were made to improve our knowledge of CACS; currently we know that cachexia arises from a complex and multifactorial interaction between various mechanisms including inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism; consequently its management requires multidisciplinary and multipharmacological approach that should address the different causes underlying this clinical event. On these premises, several drugs have been proposed starting from the first pharmacological treatment based on progestational agents or corticosteroids; most of them are in the preclinical phase, but some have already reached the clinical experimentation stage. In conclusion, to date, there is no standard effective treatment and further studies are needed to unravel the basic mechanisms underlying CACS and to develop newer therapeutic strategies with the hope to improve the quality of life of pancreatic cancer patients.

  5. [Current Approaches in Cancer Immunotherapy].

    Science.gov (United States)

    Otáhal, P; Trněný, M

    2015-01-01

    Methods of cancer immunotherapy have finally entered clinical medicine after years of preclinical research. Currently, there are several methods, which have proven to be very effective even in cases of incurable cancer. Antitumor monoclonal antibodies are among major therapeutic anti-cancer drugs and have been successfully used for many ears. Novel group of antibodies are immunomodulatory antibodies which can break tumor -specific immune tolerance and induce regression of tumors by nonspecific activation of immune system. Bispecific antibodies represent a novel class of anticancer agents which can induce expansion of T cells in vivo, blinatumomab is an example of such agents and is currently available for the treatment of acute B -cell leukemia. Cellular immunotherapy is also very effective, especially the use of Chimeric receptor modified T-cells for the therapy of B- cell lymphoproliferative diseases. Although it is a very complicated and expensive method, it is highly effective approach which can induce remission even in previously hopeless conditions. The goal of this article is to explain the basic principles of cancer immunotherapy and summarize the newest findings in this field.

  6. [Exploration of research approaches of Chinese medicine's pharmacology based on "imprinting templates" (medical element) of supramolecules].

    Science.gov (United States)

    He, Fu-yuan; He, Hong; Deng, Kai-wen; Zhou, Yi-qun; Shi, Ji-lian; Liu, Wen-long; Yang, Yan-tao; Tang, Yu

    2015-11-01

    The paper, based on the previous publication as special impact of Chinese medicine theories on supramolcular chemistry, aims to analyze the natural origination for the Chinese medicine and to explain the special impact of "Qi chromatography" reaction on "imprinting templates" in supramolcular host of human being with Chinese medicine, in order to reveal the CM's properties of "medical element" with "imprinting templates" autonomisation generally took place in natural supramolecules, and also to discover that the CM's pharmacology are satisfied with its own approaches different form western pharmacology. It was decided, for CM's pharmacology guided by CM's theories, to "Qi chromatography" relations between the CM's ingredient groups and the meridian zang-fu viscera. The supramolcular chemistry played an all-through role in procession of making macro-regularities and special presentation on behavior of "Qi chromatography" impulse owning to the matching action of all kinds of ingredients on the meridian zang-fu viscera with similar "imprinting templates". The CM's pharmacology were guided by CM's theories, owing to its interpretation of supramolecular chemistry. The pharmacology was achieved to construct up completely on base of classical chemical single molecular bonds whereas the CM's pharmacology be configured to big building by way of "imprinting templates" as multi-weak bonds among "supramolecular society". CM's pharmacology was supramolcular pharmacology dealt with "molecular society" on the base of western pharmacology, and employed to double research approaches both math-physical quantitative representation on macroscope and qualitative analyses in microscope.

  7. Current clinical approach to achalasia

    Institute of Scientific and Technical Information of China (English)

    Alexander J Eckardt; Volker F Eckardt

    2009-01-01

    Idiopathic achalasia is a rare primary motility disorder of the esophagus.The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus.These motor abnormalities lead to dysphagia,stasis,regurgitation,weight loss,or secondary respiratory complications.Although major strides have been made in understanding the pathogenesis of this rare disorder,including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals,a definite trigger has not been identified.The diagnosis of achalasia is suggested by clinical features and confirmed by further diagnostic tests,such as esophagogastroduodenoscopy (EGD),manometry or barium swallow.These studies are not only used to exclude pseudoachalasia,but also might help to categorize the disease by severity or clinical subtype.Recent advances in diagnostic methods,including high resolution manometry (HRM),might allow prediction of treatment responses.The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods.Although limited high-quality data exist,it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients.However,the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease,but also on local expertise and patient preferences.

  8. Extending worldwide clinical pharmacology education through a pricing approach.

    Science.gov (United States)

    Ameer, Barbara

    2005-09-01

    Financial instruments, such as professional membership fees, are part of the science and technology policy toolkit for creating an environment conducive to developing an international health knowledge network. To minimize a hurdle to global knowledge exchange in clinical pharmacology, the American College of Clinical Pharmacology reevaluated fees for its international members. Secondary market research was conducted on salary data available from US-based multinational firms. Salary comparisons for the same position based in the United States and in a developing economy were used to generate an index ratio. Applying this ratio, a tiered-membership fee structure was constructed for the approximately 120 countries where gross national income meets the World Bank classification of "developing economy." The index ratio serves as a paradigm for structuring fees across a variety of programs. With the implementation of an adjusted dues structure, information and networks of colleagues are now more accessible to clinical pharmacologists in developing economies.

  9. Perspectives and Trends in Pharmacological Approaches to the Modulation of Pain.

    Science.gov (United States)

    Barrett, James E; Haas, Derick A

    2016-01-01

    Pharmacological approaches to our understanding and treatment of pain have had a long history and have traditionally relied on very few drugs that either have significant side effects and abuse liability, such as the nonsteroidal anti-inflammatory drugs or the opioids, respectively, or those that have been developed for other conditions such as the tricyclic antidepressants. The pathophysiology of pain is undoubtedly complex, complicated in part by the fact that it is not a singular condition, and has a variety of etiologies and a number of associated comorbidities that make treatment interventions challenging. Moreover, there are changes in the central nervous system during the course of the development of chronic pain that, in a manner parallel to neurodegenerative disorders, likely require different pharmacological approaches in the early stages of acute pain compared to those that would be effective when pain has become chronic. This chapter reviews the current status of the field of pain research focusing on some relatively underdeveloped areas, such as pain and its associated comorbidities, and the use of transgenic animals and drug self-administration procedures in the context of analgesic assessment. This chapter also incorporates more recent developments and emerging trends in the area of epigenetics, biomarkers, and the use of induced pluripotent stem cells for pharmacological evaluation, target identification, and validation. Recent progress in the study of "organs-on-a-chip" will also be included in this overview, setting expectations for future progress that integrates these advances for deeper insights into mechanisms, novel treatments, and facilitated efforts in drug discovery.

  10. Current understanding of TRPM7 pharmacology and drug development for stroke

    Institute of Scientific and Technical Information of China (English)

    Christine You Jin BAE; Hong-shuo SUN

    2013-01-01

    The initial excitement and counties efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials.Currently,a thrombolytic agent called recombinant tissue plasminogen activator (rtPA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries.Even though its efficacy has been confirmed repeatedly,rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use.A search for alternative mechanisms that may operate dependently or independently with the well-established excitotoxic mechanism has led researchers to the discovery of newly described non-glutamate mechanisms.Among the latter,transient receptor potential melastatin 7 (TRPM7) is one of the important nonglutamate mechanisms in stroke,which has been evaluated in both in-vitro and in-vivo.In this review,we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.

  11. Cognitive enhancement in schizophrenia: pharmacological and cognitive remediation approaches.

    Science.gov (United States)

    Harvey, Philip D; Bowie, Christopher R

    2012-09-01

    This article discusses the measurement of cognition in schizophrenia, its role as a determinant of disability, and treatment efforts to date, including pharmacological and behavioral interventions as well as effective treatments that lead to improved outcomes. The measurement of functioning when patients with schizophrenia receive treatment in the office is addressed. The review focuses on new developments in the creation and adoption of a consensus method for the assessment of cognitive functioning in treatment studies, on the increased appreciation for assessment of functional skills in the prediction of everyday outcomes, and on developments in the basic neuroscience of cognition.

  12. 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.

  13. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Institute of Scientific and Technical Information of China (English)

    Khaled; Mohamed; Mohamed; Koriem

    2015-01-01

    Anisi aetheroleum is the oil obtained from Pimpinella anisuin L.(P.anisuin) by steam distillation.P.anisuin seeds were air-dried,and then the dry seeds were crushed,pulverized,and weighed in sequence for anise oil preparation.P.anisuin is one of the oldest medicinal plants that belong to family Apiaceae.The fruit of P.anisuin is harvested in August and September.P.anisuin is widespread in Asia,Africa and Europe.Local names of P.anisuin 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.transAnethole 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.

  14. Pharmacological approaches to manage persistent symptoms of major depressive disorder: rationale and therapeutic strategies.

    Science.gov (United States)

    Epstein, Irvin; Szpindel, Isaac; Katzman, Martin A

    2014-12-01

    Major depressive disorder (MDD) is a highly prevalent chronic psychiatric illness associated with significant morbidity, mortality, loss of productivity, and diminished quality of life. Typically, only a minority of patients responds to treatment and meet criteria for remission as residual symptoms may persist, the result of an inadequate course of treatment and/or the presence of persistent side effects. The foremost goal of treatment should be to restore patients to full functioning and eliminate or relieve all MDD symptoms, while being virtually free of troublesome side effects. The current available pharmacological options to manage persistent depressive symptoms include augmentation or adjunctive combination strategies, both of which target selected psychobiological systems and specific mood and somatic symptoms experienced by the patient. As well, non-pharmacological interventions including psychotherapies may be used in either first-line or adjunctive approaches. However, the evidence to date with respect to available adjunct therapies is limited by few studies and those published have utilized only a small number of subjects and lack enough data to allow for a consensus of expert opinion. This underlines the need for further longer term, large population-based studies and those that include comorbid populations, all of which are seen in real world community psychiatry.

  15. Novel Pharmacologic Approaches for the Management of Diabetic Retinopathy

    Science.gov (United States)

    Kovach, Jaclyn L.; Schwartz, Stephen G.

    2010-01-01

    Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy. PMID:20352067

  16. 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.

  17. 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...

  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...

  19. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Sugimoto, Keiichiro; Inui, Hiroshi; Fukusato, Toshio

    2015-04-07

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers (thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.

  20. Pharmaceutical and pharmacological approaches for bioavailability enhancement of etoposide

    Indian Academy of Sciences (India)

    Ishtiyaq Ahmad Najar; Rakesh Kamal Johri

    2014-03-01

    Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful antineoplastic agent used routinely in firstline combination chemotherapy of testicular cancer, small-cell lung cancer and non-Hodgkin’s lymphoma. Etoposide displays narrow therapeutic index, erratic pharmacokinetics and dose individualization that needs to be achieved for overcoming inter- and intra-patient variability (25–80%), so as to maintain proper drug exposure within a therapeutic range. Etoposide posses high plasma protein binding (97%) and is degraded via complex metabolic pathways. The main pharmacokinetic determinants of etoposide are still not completely defined in order to optimize the pharmaco-therapeutic parameters including dose, therapeutic schedule and route of administration. 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 of etoposide.

  1. Carious dentine removal: current approach

    Directory of Open Access Journals (Sweden)

    Germana Coeli de Farias Sales

    2008-01-01

    Full Text Available Dentistry is renewed day after day through the results of qualified researches. The approach as regards carious dentin removal is goingthrough questioning and innovation. The scope of this study was to perform a literature review in the sense of elucidating questions pertaining to the problem of whether or not it is necessary to completely remove carious dentin, and the possibility of performing restoration in a single session, in addition to a discussion about which type of material should be applied in this type of substrate. After analyzing the referenced articles, it was concluded that the stepwise treatment controls caries progression; there is a trend in the literature to partially remove the carious dentin in deep lesions and perform definitive restoration; Calcium hydroxide cement is a classical liner in these situations, while glass ionomer cement and resinous materials are other possibilities of materials that can be in close contact with the remaining dentin.

  2. 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.

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

    Science.gov (United States)

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

    2017-08-08

    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 goal 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.

  4. [New pharmacological approaches to the treatment of schizophrenia].

    Science.gov (United States)

    Uzbay, I Tayfun

    2009-01-01

    Schizophrenia is a serious mental disorder with a challenging rational pharmacotherapy. Neurochemical transmission in the dopaminergic system, especially via D2 receptors, and related changes in postsynaptic signal transduction are very important in both the formation of schizophrenia and current pharmacotherapeutic treatment with antipsychotic drugs. Blocking the serotonergic 5-HT2A and 5-HT2C receptors is growing growing importance with regard to the action mechanisms of new generation antipsychotic medications. Recent preclinical and clinical data show that dysfunction of central neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurophin-3 (NT-3) might contribute to impaired brain development and neuroplasticity, leading to schizophrenia. In addition, some recent studies suggest that there is an important relationship between alcohol and substance addiction, and schizophrenia. There is also some preclinical data indicating that the central nitrergic system and agmatine(3/4)a biologically active agent produced after decarboxylation of arginine(3/4)might be interesting and important targets for understanding the etiopathogenesis of schizophrenia and for development of new drugs. Selective dopamine D3 receptor antagonists, specific agonists for metabotropic and NMDA receptors of the glutamatergic system, and nicotinic alpha-7 receptor agonists were reported in preclinical and a limited number of clinical studies as potential new targets for schizophrenia treatment. In this review, new advances in the pharmacotherapy of schizophrenia and possible new targets are discussed in the light of the current literature.

  5. Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.

    Science.gov (United States)

    Yu, J; Cilfone, N A; Large, E M; Sarkar, U; Wishnok, J S; Tannenbaum, S R; Hughes, D J; Lauffenburger, D A; Griffith, L G; Stokes, C L; Cirit, M

    2015-10-01

    Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response--focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four-MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi-MPS interactome operation and experiments.

  6. Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?

    Science.gov (United States)

    Pirozzi, Luisella; Sountoulides, Petros; Castellan, Pietro; Presicce, Fabrizio; Lombardo, Riccardo; Romero, Marilena; De Nunzio, Cosimo; Tubaro, Andrea; Schips, Luigi; Cindolo, Luca

    2015-01-01

    Benign prostatic hyperplasia (BPH) is a potentially progressive disease which is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. In the current medical therapy scenario for LUTS attributed to BPH, only one class of drugs, 5-α reductase inhibitors (5ARIs), has been found to be effective in reducing the risk of disease progression. The two 5ARIs that are currently available include finasteride and dutasteride. These two drugs have different pharmacokinetic and pharmacodynamic properties. Greater suppression of dehydrotestosterone is achieved by dutasteride (>90% dutasteride vs 70% finasteride) which theoretically should correlate with greater efficacy in alleviating urinary symptoms. Unfortunately, this hypothesis has not yet been clinically demonstrated. The pertinent literature is scarce and heterogeneous and produces low scientific levels of evidence. The present review article aims to evaluate the comparative head-to-head studies in order to evaluate if the hypothetical clinical differences between dutasteride and finasteride do exist. Pharmacological treatment with either drug results in similar symptom improvements; however dutasteride seems to have a better profile in reducing the risk of prostate surgery and acute urinary retention (AUR). More studies are necessary to better evaluate both the clinical and pharmacoeconomic profile of the two 5ARIs.

  7. [The teaching of pharmacology in medical schools: current status and future perspectives].

    Science.gov (United States)

    Rodríguez-Carranza, Rodolfo; Vidrio, Horacio; Campos-Sepúlveda, Efraín

    2008-01-01

    Pharmacology is a core course in all medical school curricula. In most medical schools, pharmacology is taught during the second year and teaching covers both basic aspects and useful drugs for the treatment of human diseases. It is assumed that relevant pharmacologic knowledge is revisited during the clinical clerkships and that students are adequately trained to prescribe drugs upon graduation. However, for many years it has been noted that pharmacological training is sometimes insufficient and that inadequate and irrational prescription of drugs is a very common problem in clinical settings. Information overload and proliferation of new drugs have been recognized as two of the major contributing factors. To address this issue, many authors have recommended the development of a core curricula in pharmacology which all students would have to complete coupled with a restricted list of drugs. Based on our own teaching experience we have identified what should constitute the core content of pharmacology courses in medical schools and have written a study guide for this discipline. Both documents provide an organizational framework to help second year medical students ascertain what part of the vast knowledge in pharmacology they need to learn. The number of drugs that students have to manage is limited to 168. Our program constitutes the first effort to medicalize the teaching of pharmacology in medical schools. We expect that most medical schools will follow our guidelines as our program is applicable to all curricula modalities.

  8. Towards patient stratification and treatment in the autoimmune disease lupus erythematosus using a systems pharmacology approach.

    Science.gov (United States)

    Ruiz-Cerdá, M Leire; Irurzun-Arana, Itziar; González-Garcia, Ignacio; Hu, Chuanpu; Zhou, Honghui; Vermeulen, An; Trocóniz, Iñaki F; Gómez-Mantilla, José David

    2016-10-30

    Drug development in Systemic Lupus Erythematosus (SLE) has been hindered by poor translation from successful preclinical experiments to clinical efficacy. This lack of success has been attributed to the high heterogeneity of SLE patients and to the lack of understanding of disease physiopathology. Modelling approaches could be useful for supporting the identification of targets, biomarkers and patient subpopulations with differential response to drugs. However, the use of traditional quantitative models based on differential equations is not justifiable in a sparse data situation. Boolean networks models are less demanding on the required data to be implemented and can provide insights into the dynamics of biological networks. This methodology allows the integration of all the available knowledge into a single framework to evaluate the behavior of the system under different conditions and test hypotheses about unknown aspects of the disease. In this proof-of-concept study, we explored the potential of a systems pharmacology model based on Boolean networks to support drug development in SLE. We focused the analysis on the antigen presentation by the antigen presenting cells (APC) to the T-cells to evaluate the scope of this methodology in a medium size network before full implementation of the whole SLE pathway. The heterogeneity of SLE patients was replicated using this methodology simulating subjects with distinct pathway alterations. A perturbation analysis of the network coupled with clustering analysis showed potential to identify drug targets, optimal combinatorial regimens and subpopulations of responders and non-responders to drug treatment. We propose this approach as a first step towards the development of more quantitative platforms to address the current challenges in drug development for complex diseases.

  9. [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.

  10. Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis.

    Science.gov (United States)

    Lewiecki, E Michael

    2009-10-01

    Postmenopausal osteoporosis is an asymptomatic skeletal disease that is often underdiagnosed and undertreated. Osteoporotic fractures are associated with substantial morbidity and mortality and impaired quality of life-socially, emotionally, and financially. Considering the growing burden of osteoporotic fractures worldwide, there remains an ongoing need for progress in the diagnosis of osteoporosis, identification of individuals at high fracture risk, and treatment to prevent fractures. Adequate intake of calcium and vitamin D is recommended as baseline therapy for osteoporosis prevention and treatment. Available pharmacological agents for the management of postmenopausal osteoporosis may not be appropriate for all women. Oral bisphosphonates are generally considered first-line therapy for patients with osteoporosis, but their use may be limited by gastrointestinal side effects. Other agents include hormone therapy, the selective estrogen receptor modulator (SERM) raloxifene, salmon calcitonin, teriparatide (human recombinant parathyroid hormone), and strontium ranelate (in some countries). Factors that may contribute to poor compliance and persistence with current osteoporosis therapies include drug intolerance, complexity of dosing regimens, and poor understanding of the relative benefit and risk with treatment. Emerging therapies for postmenopausal osteoporosis include novel SERMs (bazedoxifene, lasofoxifene, ospemifene, arzoxifene) and denosumab. Because SERMs can display mixed functional estrogen receptor agonist or antagonist activity depending on the target tissue, they may confer beneficial effects on bone with limited stimulation of other tissues (e.g., breast, endometrium). Clinical investigation of these promising new agents is ongoing to evaluate efficacy and safety, with the goal of developing effective strategies to maximize long-term tolerance, compliance, and persistence with therapy.

  11. 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.

  12. Pharmacological and analytical aspects of withaferin A:A concise report of current scientific literature

    Institute of Scientific and Technical Information of China (English)

    Kanika Patel; Ravi B Singh; Dinesh K Patel

    2013-01-01

    Withaferin A is an important phytoconstituents of Withania somnifera (W. Somnifera) belonging to the category of withanolides, that are a group of naturally occurring C28-steroidal lactone triterpenoids. Withaferin A has been used in the traditional and indigenous system of medicine for the treatment of various disorders. In view of its unique therapeutic potential, it has gained much attention in the modern science. In the couple of the years, Withaferin A has been scientifically validated for different pharmacological activities including anti-cancer, adaptogenic, anti-stress, anti-convulsant, immunomodulatory, neurological, anti-inflammatory, anti-tumor, cardioprotective, and neuroprotective activities. Pharmacological and analytical aspects of Withaferin A were highlighted in the present article. From the literature review it was found that Withaferin A has a very impressive pharmacological profile especially against cancer and could be useful for the development of the new drug in the future for the treatment of cancer and other metabolic disorders.

  13. Reverse Pharmacognosy and Reverse Pharmacology; Two Closely Related Approaches for Drug Discovery Development.

    Science.gov (United States)

    Saeidnia, Soodabeh; Gohari, Ahmad R; Manayi, Azadeh

    Pharmacognosy is a science, which study natural products as a source of new drug leads and effective drug development. Rational and economic search for novel lead structures could maximize the speed of drug discovery by using powerful high technology methods. Reverse pharmacognosy, a complementary to pharmacognosy, couples the high throughput screening (HTS), virtual screening and databases along with the knowledge of traditional medicines. These strategies lead to identification of numerous in vitro active and selective hits enhancing the speed of drug discovery from natural sources. Besides, reverse pharmacology is a target base drug discovery approach; in the first step, a hypothesis is made that the alteration of specific protein activity will produce beneficial curative effects. Both, reverse pharmacognosy and reverse pharmacology take advantages of high technology methods to accomplish their particular purposes. Moreover, reverse pharmacognosy effectively utilize traditional medicines and natural products as promising sources to provide new drug leads as well as promote the rational use of them by using valuable information like protein structure databases and chemical libraries which prepare pharmacological profile of traditional medicine, plant extract or natural compounds.

  14. Pharmacologic inhibition of intestinal sodium uptake: a gut centric approach to sodium management.

    Science.gov (United States)

    Spencer, Andrew G; Greasley, Peter J

    2015-09-01

    Impaired sodium excretion in patients with chronic kidney disease (CKD) can drive fluid overload and hypertension and accelerate CKD progression. Diuretics reduce fluid overload but require residual kidney function to work. Adherence to dietary sodium restriction is generally poor. Here, we review an alternative pharmacologic strategy aimed at reducing sodium absorption from the gut. Genetic studies implicate the sodium/hydrogen exchanger isoform 3 (NHE3) as the major absorptive sodium transporter. Pharmacologic inhibition of apically expressed gut NHE3 offers the potential of reducing sodium absorption and fluid overload independent of kidney function and with better safety than systemic drugs. Two small-molecule inhibitors of NHE3 (tenapanor and SAR218034) with minimal systemic exposure reduce urinary sodium and increase stool sodium in a dose-dependent manner in rodents, with similar results observed with tenapanor in humans. These molecules also reduce blood pressure in rat models of CKD (tenapanor) and hypertension (SAR218034). Clinical trials of tenapanor in patients with CKD-related disorders are ongoing. Pharmacologic inhibition of gut NHE3 may be a viable strategy for managing sodium load in patients with CKD or with sodium-sensitive hypertension in general. Ongoing clinical trials will shed further light on the potential benefits of this approach.

  15. Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

    Science.gov (United States)

    Qi, Quan; Li, Rui; Li, Hui-ying; Cao, Yu-bing; Bai, Ming; Fan, Xiao-jing; Wang, Shu-yan; Zhang, Bo; Li, Shao

    2016-01-01

    Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The anti-tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including “regulation of lipase activity”, “response to nicotine” and “regulation of cell proliferation”. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels. PMID:27180984

  16. Pharmacological vs. classical approaches in the design of first in man clinical drug trials.

    Science.gov (United States)

    van den Bogert, Cornelis A; Cohen, Adam F; Leufkens, Hubert G M; van Gerven, Joop M A

    2017-10-04

    The aims of the present study were to investigate the role of pharmacology in the design of first-in-man (FIM) trials in the Netherlands, and to evaluate the change in design approaches between 2007 and 2015. All FIM drug trials approved by all Dutch Institutional Review Boards (IRBs) in 2007 and in 2015 were selected. The original trial protocols, investigator's brochures and investigational medicinal product dossiers were the data sources. The following four design elements were assessed on the justification of the chosen approaches: preclinical information, dose calculation, endpoints, and dose escalation. In 2007, the Dutch IRBs approved 21 FIM trials, and in 2015 they approved 34 FIM trials (55 in total). Seven out of 21 (33%) of the FIM trials from 2007, and 14 out of the 34 (41%) FIM trials from 2015 discussed only the no-observed-adverse-effect level or no-observed-effect level as preclinical information. Furthermore, five of the 21 (24%) 2007 FIM trials and 12 of the 34 (35%) 2015 FIM trials used unexplained allometric scaling. Pharmacodynamic (PD) parameters were measured in 15 of the 21 (71%) 2007 FIM trials and in 31 of the 34 (91%) of the 2015 FIM trials, and allometric scaling was only guided by safety/tolerability in 11 of the 20 (55%) dose escalation trials in 2007 and in nine of the 33 (27%) dose escalation trials in 2015. Trial protocols and investigator's brochures commonly lack pharmacokinetic/PD approaches. Investigators, sponsors and IRBs should require an upfront consideration of pharmacology in these aspects for all FIM trials. © 2017 The British Pharmacological Society.

  17. 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.

  18. A new pharmacological approach to gastrointestinal cancer at high risk of relapse based on maintenance of the cytostatic effect.

    Science.gov (United States)

    Nicolini, Andrea; Conte, Massimo; Rossi, Giuseppe; Ferrari, Paola; Carpi, Angelo; Miccoli, Paolo

    2010-10-01

    In metastatic colorectal and other locally advanced gastrointestinal cancers, the mechanisms of tumor growth and/or immune escape by residual cancer cells after curative resection often provoke tumor recurrence. Current adjuvant therapy is based on pharmacological administration up to 6-8 months after surgery. We hypothesized that the long-term, cytostatic action from repeated post-adjuvant administration of 5-fluorouracil (FU)-leucovorin (LV) cycles, as a result of the downregulation of the above-mentioned cellular mechanisms, could halt tumor progression. An active prospective cohort, including 19 patients (study group) at high risk of relapse, was considered. All patients received repeated post-adjuvant administration of 5-FU-LV cycles for up to 52-60 months following curative surgery (total cumulative dose of about 90 g and mean follow-up of 70.6 ± 49.7 months). The 5-year disease-free interval (DFS) and overall survival (OS) were 80.4 ± 10.2% and 87.1 ± 8.6%, respectively, which is very different from the recent literature that has reported 5-year DFS and OS values of 31.8% and 40.1%, respectively. These findings suggest that this new pharmacological approach based on the long-term maintenance of a cytostatic effect with 5-FU-LV can produce a relevant improvement in the outcome of this population.

  19. Systems Pharmacology Approaches for Optimization of Antiangiogenic Therapies: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Satish eSharan

    2015-02-01

    Full Text Available Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these therapies impedes the successful management of advanced cancer. Due to the redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses of the agents lead to greater stimulation of compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF-targeted drugs and produce escape mechanisms for tumor. Evidence suggests that dose intensity and schedules affect the dynamics of the development of this resistance. Thus, an optimal dosing regimen is crucial to maximizing the therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers and their impacts on tumor reduction and resistance. Herein, we discuss a systems pharmacology approach integrating the biology of VEGF-targeted therapy resistance, including circulating biomarkers, and pharmacodynamics to enable the optimization of antiangiogenic therapy for therapeutic gains.

  20. The trigonometric responder approach: a new method for detecting responders to pharmacological or experimental challenges.

    Science.gov (United States)

    Reuter, M; Siegmund, A; Netter, P

    2002-09-01

    The paper presents a newly developed response measure that is particularly suitable for the evaluation of pharmacokinetic data. This method is based on trigonometric considerations, defining a hormone response as the difference between the angle of the slope of the curve before and after drug intake. In addition, the size of this difference is compared to the difference obtained in placebo conditions. In this way, the trigonometric response measure overcomes one of the most problematic shortcomings of the 'area under the curve' (AUC) approach, the problem of the initial value. We will present the mathematical background of the trigonometric method and demonstrate its usefulness by evaluating empirical data (a pharmacological challenge test using the dopamine agonist lisuride) and comparing it to classical AUC measures. This has been achieved by contrasting both approaches with responder definitions according to binary time series analysis and the peak value of the curve.

  1. 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.

  2. Current state of knowledge on the traditional uses, phytochemistry, and pharmacology of the genus Hymenaea.

    Science.gov (United States)

    Boniface, Pone Kamdem; Baptista Ferreira, Sabrina; Roland Kaiser, Carlos

    2017-07-12

    Plants of the genus Hymenaea (Fabaceae) are used in South American and Asian traditional medicines to treat a multitude of disorders, like cough, diarrhea, dysentery, intestinal colic, pulmonary weakness, asthma, anemia, sore throat, and for the treatment of kidney problems, viral related disorders, chronic cystitis, bronchitis, and bladder infections. Some Hymenaea species are also used as vermifuge, and for the treatment of arthritis, and inflammation conditions. This review deals with updated information on the traditional uses, phytochemistry and pharmacology of ethnomedicinally important Hymenaea species in order to provide an input for the future research prospects. Literature available in various recognized databases including Google Scholar, PubMed, SciFinder, Scopus, Springer, Wiley, ACS, Scielo and Web of Science, as well as from theses, dissertations, books, reports, and other relevant websites (www.theplantlist.org), are surveyed, analysed, and included in this review. Herein, the literature related to chemical constituents and pharmacological activities were searched in November 2016. The literature provided information on ethnopharmacological uses of the South American and African species of the genus Hymenaea (e.g., H. courbaril, H. stigonocarpa, H. onblogifolia, H. martiana, H. parvifolia (South America) and H. verrucosa (African species)) for the treatment of multi-factorial diseases. From these plant species, more than 130 compounds, including fatty acids, flavonoids, terpenoids and steroids, phthalides, phenolic acids, procyanidins and coumarins were identified. Experimental evidences confirmed that the Hymenaea spp. could be used in treating inflammatory disorders, asthma, diarrhea, and some microbial infections. However, reports on the toxicity of Hymenaea species remain scarce. Plants of this genus have offered bioactive samples, both from crude extracts and pure compounds, thus substantiating their effectiveness in traditional medicine

  3. 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.

  4. Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

    Science.gov (United States)

    Yue, Shi-Jun; Xin, Lan-Ting; Fan, Ya-Chu; Li, Shu-Jiao; Tang, Yu-Ping; Duan, Jin-Ao; Guan, Hua-Shi; Wang, Chang-Yun

    2017-01-01

    Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

  5. 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...

  6. Pharmacological treatment of endometriosis: review of current and new options for treatment

    Directory of Open Access Journals (Sweden)

    Maja Jakič

    2016-10-01

    Full Text Available Endometriosis is a gynecological disease that is defined as the presence of endometrium-like tissue outside the uterine cavity, and it is one of the main causes of female infertility. Although there is unfortunately no known ‘optimal’ treatment for endometriosis, there are three treatment options: medication, surgical treatment, and a combination of both. The gold standard for diagnosis of endometriosis is a diagnostic laparoscopy, which is also therapeutic. Indications for pharmacological treatment of endometriosis include empirical treatment for patients with pelvic pain who are normal on gynecological examination, or who have recurrent disease after surgical treatment or in combination with surgical treatment. In everyday practice, non-steroid anti-inflammatory drugs, oral contraceptives, and progestins per os are used as first-line pharmacological treatments of endometriosis. Gonadoliberin agonists can be used as second-line treatment, although their use is discouraged. These medications can be used alone or in combination. Studies over the last 10 years have shown that many other agents have potential for treatment of endometriosis. These can be broadly classified into several groups: anti-inflammatory agents, and agents that interfere with the hormonal system, or with other pathophysiological processes, such as a disturbed immune system, reduced apoptosis, enhanced angiogenesis, degradation of the extracellular matrix, increased oxidative stress, and epigenetic changes. However, their introduction into routine use requires more convincing clinical studies to confirm their effectiveness.

  7. Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era.

    Science.gov (United States)

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Reiter, Russel J

    2014-03-26

    In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification of several promising pharmacological (cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.

  8. Buspirone: review of its pharmacology and current perspectives on its mechanism of action.

    Science.gov (United States)

    Eison, A S; Temple, D L

    1986-03-31

    Buspirone is a novel anxiolytic agent unrelated to the benzodiazepines in structure or pharmacologic properties. Extensive clinical studies have shown buspirone to be effective in the treatment of anxiety, with efficacy comparable to diazepam or clorazepate. Buspirone exhibits a unique pharmacologic profile in that it alleviates anxiety without causing sedation or functional impairment and does not promote abuse or physical dependence. Furthermore, preclinical studies have shown that buspirone does not possess anticonvulsant or muscle relaxant properties and does not interact significantly with central nervous system depressants. Biochemical and electrophysiologic studies indicate that buspirone alters monoaminergic and GABAergic systems in a manner different from that of the benzodiazepines. The uniform depressant action of the benzodiazepines upon serotonergic, noradrenergic, and dopaminergic cell firing may result from their facilitatory effect on gamma-aminobutyric acid and its known inhibitory influence in these monoaminergic areas. Unlike the benzodiazepines, buspirone exerts a differential influence upon monoaminergic neuronal activity, suppressing serotonergic activity while enhancing dopaminergic and noradrenergic cell firing. The mechanism of action of buspirone challenges the notion that only one neurotransmitter mediates anxiety. The interaction with multiple neurotransmitters at multiple brain sites suggests that buspirone may alter diverse activities within a "neural matrix of anxiety." In contrast to the benzodiazepines, buspirone orchestrates activity within this neural matrix to achieve effective treatment of anxiety while preserving arousal and attentional processes.

  9. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus.

    Science.gov (United States)

    Tahrani, Abd A; Barnett, Anthony H; Bailey, Clifford J

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

  10. Anti-Inflammatory Nutrition as a Pharmacological Approach to Treat Obesity

    Directory of Open Access Journals (Sweden)

    Barry Sears

    2011-01-01

    Full Text Available Obesity is a multifactorial condition resulting from improper balances of hormones and gene expression induced by the diet. Obesity also has a strong inflammatory component that can be driven by diet-induced increases in arachidonic acid. The purpose of this paper is to discuss the molecular targets that can be addressed by anti-inflammatory nutrition. These molecular targets range from reduction of proinflammatory eicosanoids to the modulation of features of the innate immune system, such as toll-like receptors and gene transcription factors. From knowledge of the impact of these dietary nutrients on these various molecular targets, it becomes possible to develop a general outline of an anti-inflammatory diet that can offer a unique synergism with more traditional pharmacological approaches in treating obesity and its associated comorbidities.

  11. Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach[S

    Science.gov (United States)

    Gadkar, Kapil; Lu, James; Sahasranaman, Srikumar; Davis, John; Mazer, Norman A.; Ramanujan, Saroja

    2016-01-01

    The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate. PMID:26522778

  12. Pharmacological profile of the ATP-mediated increase in L-type calcium current amplitude and activation of a non-specific cationic current in rat ventricular cells.

    OpenAIRE

    Scamps, F.; Vassort, G.

    1994-01-01

    1. The pharmacological profile of the ATP-induced increase in ICa amplitude and of ATP activation of a non-specific cationic current, IATP, was investigated in rat ventricular cells. 2. The EC50 values for ICa increase and IATP activation were 0.36 microM and 0.76 microM respectively. Suramin (10 microM) and cibacron blue (1 microM) competitively antagonized both effects of ATP. 3. The rank order of efficacy and potency of ATP analogues in increasing ICa amplitude was 2-methylthio-ATP approxi...

  13. Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents.

    Directory of Open Access Journals (Sweden)

    Takayoshi Yamaza

    Full Text Available BACKGROUND: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. METHODS AND FINDINGS: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX-induced osteoporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. CONCLUSION: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts.

  14. Identifying ligands at orphan GPCRs: current status using structure-based approaches.

    Science.gov (United States)

    Ngo, Tony; Kufareva, Irina; Coleman, James Lj; Graham, Robert M; Abagyan, Ruben; Smith, Nicola J

    2016-10-01

    GPCRs are the most successful pharmaceutical targets in history. Nevertheless, the pharmacology of many GPCRs remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore the physiological functions and pharmacological potential of these 'orphan' GPCRs, whether they are endogenous and/or surrogate ligands, are therefore of paramount importance. Rates of receptor deorphanization determined by traditional reverse pharmacology methods have slowed, indicating a need for the development of more sophisticated and efficient ligand screening approaches. Here, we discuss the use of structure-based ligand discovery approaches to identify small molecule modulators for exploring the function of orphan GPCRs. These studies have been buoyed by the growing number of GPCR crystal structures solved in the past decade, providing a broad range of template structures for homology modelling of orphans. This review discusses the methods used to establish the appropriate signalling assays to test orphan receptor activity and provides current examples of structure-based methods used to identify ligands of orphan GPCRs. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

  15. The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells.

    OpenAIRE

    Halliday, F. C.; Aaronson, P. I.; Evans, A. M.; Gurney, A M

    1995-01-01

    1. Using the whole-cell patch-clamp technique, the effects of several K+ channel blocking drugs on K+ current recorded from rabbit isolated aortic smooth muscle cells were investigated. 2. Upon depolarization from -80 mV, outward K+ current composed of several distinct components were observed: a transient, 4-aminopyridine (4-AP)-sensitive component (I1) and a sustained component (Isus), comprising a 4-AP-sensitive delayed rectifier current (IK(V)), and a noisy current which was sensitive to ...

  16. 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

  17. 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,…

  18. Inactivation kinetics and pharmacology distinguish two calcium currents in mouse pancreatic B-cells

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, W.F.; Satin, L.S.; Cook, D.L. (Univ. of Washington School of Medicine, Seattle (USA))

    1991-02-01

    Voltage-dependent calcium currents were studied in cultured adult mouse pancreatic B-cells using the whole-cell voltage-clamp technique. When calcium currents were elicited with 10-sec depolarizing command pulses, the time course of inactivation was well fit by the sum of two exponentials. The more rapidly-inactivating component had a time constant of 75 +/- 5 msec at 0 mV and displayed both calcium influx- and voltage-dependent inactivation, while the more slowly-inactivating component had a time constant of 2750 +/- 280 msec at 0 mV and inactivated primarily via voltage. The fast component was subject to greater steady-state inactivation at holding potentials between -100 and -40 mV and activated at a lower voltage threshold. This component was also significantly reduced by nimodipine (0.5 microM) when a holding potential of -100 mV was used, whereas the slow component was unaffected. In contrast, the slow component was greatly increased by replacing external calcium with barium, while the fast component was unchanged. Cadmium (1-10 microM) displayed a voltage-dependent block of calcium currents consistent with a greater effect on the high-threshold, more-slowly inactivating component. Taken together, the data suggest that cultured mouse B-cells, as with other insulin-secreting cells we have studied, possess at least two distinct calcium currents. The physiological significance of two calcium currents having distinct kinetic and steady-state inactivation characteristics for B-cell burst firing and insulin secretion is discussed.

  19. 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

  20. Systems Pharmacology Approach for Prediction of Pulmonary and Systemic Pharmacokinetics and Receptor Occupancy of Inhaled Drugs

    Science.gov (United States)

    Evans, N; Chappell, M; Lundqvist, A; Ewing, P; Wigenborg, A; Fridén, M

    2016-01-01

    Pulmonary drug disposition after inhalation is complex involving mechanisms, such as regional drug deposition, dissolution, and mucociliary clearance. This study aimed to develop a systems pharmacology approach to mechanistically describe lung disposition in rats and thereby provide an integrated understanding of the system. When drug‐ and formulation‐specific properties for the poorly soluble drug fluticasone propionate were fed into the model, it proved predictive of the pharmacokinetics and receptor occupancy after intravenous administration and nose‐only inhalation. As the model clearly distinguishes among drug‐specific, formulation‐specific, and system‐specific properties, it was possible to identify key determinants of pulmonary selectivity of receptor occupancy of inhaled drugs: slow particle dissolution and slow drug‐receptor dissociation. Hence, it enables assessment of factors for lung targeting, including molecular properties, formulation, as well as the physiology of the animal species, thereby providing a general framework for rational drug design and facilitated translation of lung targeting from animal to man. PMID:27104089

  1. Current Cognitive Approaches to Childhood Psychopathology.

    Science.gov (United States)

    Garfield, Sol L., Ed.

    1984-01-01

    Presents six developmentally oriented articles on childhood psychopathology. Reviews research dealing with autism, social isolation, interpersonal understanding, sociomoral reasoning, cognitive controls, and aggression and includes an overview of progress and problems in the cognitive approach to clinical child psychology. (JAC)

  2. Pharmacological and physiological properties of the after-hyperpolarization current of bullfrog ganglion neurones.

    Science.gov (United States)

    Goh, J W; Pennefather, P S

    1987-12-01

    1. The slowly decaying, calcium-dependent after-hyperpolarization (a.h.p.) that follows action potentials in bullfrog ganglion B cells has previously been shown to be generated by a potassium current called IAHP. We have recorded IAHP using a switched, single-electrode hybrid clamp where current-clamp mode was changed to voltage-clamp mode immediately after repolarization of a spike or the last spike of a train. 2. Reduction of extracellular calcium reduced the decay time of IAHP following a single spike. At all levels of extracellular calcium tested (0.5-4 mM), the decay time of IAHP was longer following a train of action potentials than following a single action potential. Thus, the time course of IAHP evoked by action potentials is a function of the calcium load induced by the action potentials. Conversely, agents that reduce the amount of IAHP activated without affecting its rate of decay, probably do not affect calcium influx. 3. Muscarine (2 or 10 microM) inhibits IAHP following an action potential by at most 30% and has no effect on decay rate of IAHP. These results suggest that muscarine has little or no effect on either calcium influx or sequestration. Decay of the a.h.p. is accelerated by muscarine but this effect is due to an increased leak conductance. 4. Charybdotoxin (CTX) between 4 and 20 nM, prolongs action potential duration in a manner consistent with blockade of the voltage- and calcium-dependent potassium current (Ic) involved in spike repolarization in these cells. This action is consistent with its reported action on analogous channels in other systems. However, CTX also reduces IAHP. Thus, in bullfrog ganglion neurones, two distinct calcium-dependent potassium currents exhibit a comparable sensitivity to CTX. This cannot be due to a decreased influx of calcium because the decay rate of IAHP following an action potential is unchanged. The action of CTX was observed with both crude and purified preparations of CTX. 5. Apamin (25 nM) and

  3. Clinical Pharmacology of Current and Future Drugs for the Acute Treatment of Migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer

    2012-01-01

    Migraine is a common disorder with a female prevalence of 17% and a male prevalence of 9%. Migraine is most often disabling and the patients need treatment of the attacks. The introduction of triptans has been a revolution for many migraine patients but only a minority of patients use...... with no more adverse events than placebo, but only one quarter of migraine patients have been pain-free after 2 hours in phase III studies. The development of current CGRP antagonists has been stopped....

  4. Primary care approaches to musculoskeletal multiple-site joint pain pharmacological therapy: a survey of general practitioners.

    Science.gov (United States)

    Raja, Rafi; Kingsbury, Sarah R; Wise, Elspeth; Conaghan, Philip G

    2014-10-01

    Chronic multiple-site joint pain (MSJP) due to osteoarthritis and soft tissue disorders is common in people over 50 years old and associated with poor outcomes. This study examined current pharmacological approaches to MSJP management in primary care. One hundred and fifty general practitioners (GPs) attending an educational seminar participated in an electronic survey (mean response rate 96%). Most GPs reported treating multiple painful joints concurrently (78%) compared with focusing on a single joint (21%). The majority believed there was no difference in analgesia for different disorders when selecting paracetamol (84%), non-steroidal anti-inflammatory drugs (NSAID)/COX-2 inhibitors (57%) or opioids (70%). When optimising therapy, intra-class optimisation (increase NSAID dose 41%, change to another NSAID/COX-2 inhibitor 30%) was preferred to inter-class step up therapy (add opioid 23%, change to opioid 6%). For NSAID gastrointestinal intolerance, the preference was to add a gastro-protective agent (74%). There is a need to better characterise MSJP and examine optimal pharmacotherapy regimens.

  5. The Medical Interaction Laboratory--Multidiscipline Approach for Presentation of Principles of Physiology and Pharmacology.

    Science.gov (United States)

    Oliver, Jack W.; Sims, Michael H.

    1979-01-01

    An interdisciplinary physiology and pharmacology course presented by the Medical Interaction Laboratory at the University of Tennessee College of Veterinary Medicine provides interaction among faculty, conserves faculty time and animal expense, and presents a coordinated laboratory experience. (BH)

  6. Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder.

    Science.gov (United States)

    Donnelly, Craig L

    2003-04-01

    should target anxiety, mood, and reexperiencing symptoms. Adrenergic agents, such as clonidine, used either alone or in combination with an SSRI may be useful when symptoms of hyperarousal and impulsivity are problematic. Supplementing with a mood stabilizer may be necessary in severe affective dyscontrol. Similarly, introduction of an atypical neuroleptic agent may be necessary in cases of severe self-injurious behavior, dissociation, psychosis, or aggression. Comorbid conditions such as ADHD should be targeted with pharmacotherapy known to be effective, such as psychostimulants or newer agents such as atomoxetine. Pharmacologic treatment of PTSD in childhood is one approach to alleviating the acute and chronic symptoms of the disorder. Despite the lack of well-designed, randomized, controlled trials that support efficacy, medication can be used in a rational and safe manner. Reduction in even one disabling symptom, such as insomnia or hyperarousal, may have a positive ripple effect on a child's overall functioning. Pharmacotherapy is typically used as one component of a more comprehensive multiple modality treatment package, including psychoeducation of the parent and child, focused exposure-based psychotherapy with adjunctive family therapy when indicated, and long-term booster interventions that use an admixture of psychodynamic, cognitive-behavioral, and pharmacologic interventions.

  7. Current approach to burn critical care.

    Science.gov (United States)

    Sakallioglu, A E; Haberal, M

    2007-10-01

    Burn trauma is a frequent cause of morbidity and mortality all over the world. Advancements in resuscitation, surgical tecniques, infection control and nutritional/metaolic support decreased mortality and morbidity. This article intends to review current outlines for initial treatment and resuscitation nutritional/metabolic support and wound management peculiar to burn patients.

  8. Physiopathological modulators of amyloid aggregation and novel pharmacological approaches in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    DEFELICE FERNANDA G.

    2002-01-01

    Full Text Available The biological mechanisms underlying the neuropathology of Alzheimer's disease (AD are complex, as several factors likely contribute to the development of the disease. Therefore, it is not surprising that a number of different possible therapeutic approaches addressing distinct aspects of this disease are currently being investigated. Among these are ways to prevent amyloid aggregation and/or deposition, to prevent neuronal degeneration, and to increase brain neurotransmitter levels. Here, we discuss possible roles of endogenous modulators of Abeta aggregation in the physiopathology of AD and some of the strategies currently under consideration to interfere with brain levels of beta-amyloid, its aggregation and neurotoxicity.

  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. Thalassemia: current approach to an old disease.

    Science.gov (United States)

    Lo, Louise; Singer, Sylvia Titi

    2002-12-01

    This article discusses the approach for recognition, diagnosis, and management of the thalassemias, and reviews new prospects of therapy, focusing mostly on the beta-thalassemias--the more severe and clinically important type, beta-thalassemia major is typically treated with regular transfusion and chelation therapy. New strategies for specific therapy including monitoring of iron induced organ damage, fetal hemoglobin augmentation as an alternative for transfusions, bone marrow transplantation offer hope for prevention of complications and better care of the beta-thalassemias.

  11. 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

  12. The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings.

    Science.gov (United States)

    Schreiber, Dominik; Klotz, Markus; Laures, Kerstin; Clasohm, Jasmin; Bischof, Michael; Schäfer, Karl-Herbert

    2014-05-01

    Pharmaceutical compounds enter the body via several major natural gateways; i.e. the lung, the skin and the gastrointestinal tract. Drug application during surgical operations can lead to severe impairment of gastrointestinal motility, which can contribute to a paralytic ileus. Here we investigated an ex vivo perfused small intestine model that allows us to ascertain the influence of pharmaceuticals upon the gut. Corresponding segments from the proximal jejunum of adult rats were used. Their mesenteric arteries and veins were cannulated and the jejunal segment excised. The individual segments were placed in a custom designed perfusion chamber and perfusion performed through the intestinal lumen as well as the mesenteric superior artery. Three test drugs, which are commonly used in anesthesiology; i.e. pentobarbital, propofol and ketamine were administered via the blood vessels. Their effects upon gastrointestinal motility patterns were evaluated by optical measurements. Longitudinal and pendular movements were distinguishable and separately analyzed. Pharmacological effects of the individual substances could be investigated. Propofol (50-200 μg/ml) was found to decrease intestinal motility, especially longitudinal movements in a dose dependent manner. Pentobarbital decreased intestinal motility only at high concentrations, above 2.5 mg/ml. A dose of 2.5 mg/ml lead to an increase in longitudinal- and pendular movements in comparison to control, while ketamine (2.5-10 mg/ml) did not alter intestinal motility at all. Histological examination of the perfused segments revealed only minor changes in tissue morphology after perfusion. The perfusion approach shown here allows for the identification of compounds which interfere with gut motility in a highly sophisticated way. It is suitable for characterization of drug and dose specific changes in motility patterns and can be used in drug development and preclinical studies.

  13. Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options.

    Science.gov (United States)

    Linnemann, Birgit; Erbe, Matthias

    2016-01-01

    The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a

  14. Current Approaches in the Treatment of Prostatitis

    Directory of Open Access Journals (Sweden)

    Volkan Izol

    2013-02-01

    Full Text Available Prostatitis is an infection or inflammation of the prostate gland that presents as several syndromes with varying clinical features. This painful condition mostly affects young and middle-aged men and diminishes their quality of life. With the recent introduction of a new classification for this disease, more effective approach for the evaluation and management of the patients with chronic pelvic pain syndrome has emerged. Nonetheless, no definitely effective treatment regime has yet been described in the literature. [Archives Medical Review Journal 2013; 22(1.000: 130-140

  15. 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.

  16. MEMS Packaging - Current Issues and Approaches

    Energy Technology Data Exchange (ETDEWEB)

    DRESSENDORFER,PAUL V.; PETERSON,DAVID W.; REBER,CATHLEEN ANN

    2000-01-19

    The assembly and packaging of MEMS (Microelectromechanical Systems) devices raise a number of issues over and above those normally associated with the assembly of standard microelectronic circuits. MEMS components include a variety of sensors, microengines, optical components, and other devices. They often have exposed mechanical structures which during assembly require particulate control, space in the package, non-contact handling procedures, low-stress die attach, precision die placement, unique process schedules, hermetic sealing in controlled environments (including vacuum), and other special constraints. These constraints force changes in the techniques used to separate die on a wafer, in the types of packages which can be used in the assembly processes and materials, and in the sealing environment and process. This paper discusses a number of these issues and provides information on approaches being taken or proposed to address them.

  17. Current endoscopic approach to indeterminate biliary strictures

    Institute of Scientific and Technical Information of China (English)

    David W Victor; Stuart Sherman; Tarkan Karakan; Mouen A Khashab

    2012-01-01

    Biliary strictures are considered indeterminate when basic work-up,including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing,are non-diagnostic.Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome.Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery,but also potential timely targeted chemotherapies.A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is,thus,paramount to avoid unnecessary surgery.Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy.Emerging data on other diagnostic modalities,such as ancillary cytology techniques,single operator cholangioscopy,and endoscopic ultrasonography-guided fine needle aspiration,revealed promising results with much improved sensitivity.

  18. Current approach to cutaneous mastocytosis in childhood.

    Science.gov (United States)

    Tamay, Zeynep; Özçeker, Deniz

    2016-09-01

    Mastocytosis is a heterogeneous disorder characterized by clonal proliferation and accumulation of mast cells in one of more organs which may lead to different clinical pictures. Pathological increase and activation of mast cells in various tissues can cause different clinical pictures. Cutaneous mastocytosis limited to the skin is the most typical clinical picture observed in children and systemic mastocytosis is very rare in the pediatric age group. The diagnosis of cutaneous mastocytosis is based on clinical findings, but is often delayed due to lack of clinical awareness of the disease and lack of its consideration in the differential diagnosis. This article focuses on the current diagnosis, management and treatment of cutaneous mastocytosis in children in order to increase awareness about this issue.

  19. Catastrophic antiphospholipid syndrome: The current management approach.

    Science.gov (United States)

    Rodriguez-Pintó, Ignasi; Espinosa, Gerard; Cervera, Ricard

    2016-04-01

    The current recommendation for catastrophic antiphospholipid syndrome (CAPS) management is the standard triple therapy with anticoagulation (AC), glucocorticoids (GCs), plasma exchange (PE), and/or intravenous immunoglobulins (IVIGs). Of note, only AC has a significant effect on the prognosis of these patients. However, from the experimental or basic point of view, there is only indirect evidence to advocate the use of these immunomodulatory therapies (GC, PE, and IVIG) in CAPS. Recently, there have been reports of severe or refractory CAPS patients treated with the monoclonal antibodies rituximab and eculizumab. The first blocks CD20, a surface protein expressed on the cytoplasmic membrane of B cells, and decreases the generation of pathogenic autoantibodies such as antiphospholipid (aPL) antibodies. The second binds with high affinity to C5 complement protein, inhibiting its cleavage and thus preventing the generation of C5b-C9 complex. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Current therapeutic approaches for plantar fasciitis

    Directory of Open Access Journals (Sweden)

    Martinelli N

    2014-03-01

    Full Text Available Nicolò Martinelli, Carlo Bonifacini, Giovanni RomeoDepartment of Ankle and Foot Surgery, IRCCS Galeazzi Orthopaedic Institute, Milan, ItalyAbstract: Almost 1 million Americans are affected by plantar fasciitis (PF, which is the commonest cause of chronic heel pain. This condition is often managed conservatively, and many rehabilitation protocols, some with the aid of orthoses, have been adopted, with good-to-excellent clinical results. Although most cases of chronic PF can be successfully managed with a conservative approach, alternative treatments, including high-energy shock wave therapy and corticosteroid injections, are commonly accepted as second-line treatment when traditional conservative therapy fails. However, surgery is still an important mode of treatment. Recently, new minimally invasive surgical techniques that offer numerous advantages (faster recovery time, early weight-bearing, lower postoperative pain over standard surgical approaches have been proposed, with good results and low complication rates. The purpose of this review is to report new conservative and surgical techniques for the treatment of PF. A literature search for articles about plantar fasciitis was conducted on the PubMed database in order to identify publications addressing the treatments of PF. The literature suggests that, initially, traditional conservative treatments consisting of rest, oral nonsteroidal anti-inflammatory drugs, foot orthotics, and stretching exercises can be tried for several weeks. In patients with chronic recalcitrant PF, extracorporeal shock wave therapy or corticosteroid injection can be considered. Surgery (minimally invasive techniques should be considered only after failure of the conservative treatments.Keywords: heel pain, surgery, plantar fasciosis

  1. 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 

  2. Non-Pharmacological Approaches to the Prevention and Treatment of Alzheimer's Disease with Respect to the Rising Treatment Costs.

    Science.gov (United States)

    Klimova, Blanka; Maresova, Petra; Kuca, Kamil

    2016-01-01

    Alzheimer's disease is a serious degenerative disease which is mainly typical of the developed countries. The prevalence percentage in Africa is only 2.6 %, whereas in America it is 6.5 % and in Western Europe 7.2 %. Overall, this disease affects 44 million people worldwide. With respect to the demographic development, a number of people suffering from Alzheimer's disease is expected in future. The key issue is not only the discovery of an effective medication, but also the early diagnosis, prevention and care about people with AD, as well as the provision of an equivalent rise of places in health and social institutions. Since the treatment of Alzheimer's disease (AD) imposes a severe economic and social burden, the main purpose of this study is to analyze and compare available non-pharmacological approaches to the prevention and treatment of patients with AD with special focus on their cognitive competences. In addition, the analysis also concentrates on the costs of pharmacological care in individual countries all over world. This is done by using Drummond's methodological approaches to direct and indirect costs. The analysis of non-pharmacological approaches is conducted on the basis of literature review of both clinical and review studies relevant for the research issue in the acknowledged databases and a comparison and evaluation of their findings.

  3. 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.

  4. 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.

  5. Pulp Regeneration: Current Approaches and Future Challenges.

    Science.gov (United States)

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    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.

  6. Pulp Regeneration: Current Approaches and Future Challenges

    Science.gov (United States)

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    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. PMID:27014076

  7. A new approach to evaluating the effects of pharmacologic vitreolysis on vitreous diffusion coefficients using dynamic light scattering

    Science.gov (United States)

    Ansari, Rafat R.; Suh, Kwang I.; Sebag, J.

    2006-02-01

    PURPOSE: Pharmacologic vitreolysis is a new approach to improve vitreo-retinal surgery. Ultimately, the development of drugs to liquefy and detach vitreous from retina should prevent disease by mitigating the contribution of vitreous to retinopathy and eliminate the need for surgery. However, the mechanism of action of pharmacologic vitreolysis remains unclear. The technique of Dynamic light scattering (DLS) was used to evaluate the effects of microplasmin by following the diffusion coefficients of spherical polystyrene nano-particles injected with microplasmin into the vitreous. METHODS: Diffusion coefficients in dissected (n=9) porcine eyes were measured in vitro. DLS was performed on all specimens at 37°C as often as every 10 minutes for up to 6 hours following injections of human recombinant microplasmin at doses ranging from 0.125 mg to 0.8 mg, with 20 nm diameter tracer nanospheres. RESULTS: DLS findings in untreated porcine vitreous were similar to the previously described findings in bovine and human vitreous, demonstrating a fast (early) component, resulting from the flexible hyaluronan molecules, and a slow (late) component, resulting form the stiff collagen molecules. Microplasmin increased porcine vitreous diffusion coefficients. A new approach was developed to use DLS measurements of vitreous diffusion coefficients to evaluate the effects of microplasmin in intact eyes. CONCLUSIONS: Pharmacologic vitreolysis with human recombinant microplasmin increases vitreous diffusion coefficients in vitro. The results of these studies indicate that this new approach using DLS to measure vitreous diffusion coefficients can be used to study the effects of pharmacologic vitreolysis using microplasmin and other agents in intact eyes and ultimately in vivo.

  8. A Systems Biology Approach to Uncovering Pharmacological Synergy in Herbal Medicines with Applications to Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Xia Wang

    2012-01-01

    Full Text Available Background. Clinical trials reveal that multiherb prescriptions of herbal medicine often exhibit pharmacological and therapeutic superiority in comparison to isolated single constituents. However, the synergistic mechanisms underlying this remain elusive. To address this question, a novel systems biology model integrating oral bioavailability and drug-likeness screening, target identification, and network pharmacology method has been constructed and applied to four clinically widely used herbs Radix Astragali Mongolici, Radix Puerariae Lobatae, Radix Ophiopogonis Japonici, and Radix Salviae Miltiorrhiza which exert synergistic effects of combined treatment of cardiovascular disease (CVD. Results. The results show that the structural properties of molecules in four herbs have substantial differences, and each herb can interact with significant target proteins related to CVD. Moreover, the bioactive ingredients from different herbs potentially act on the same molecular target (multiple-drug-one-target and/or the functionally diverse targets but with potentially clinically relevant associations (multiple-drug-multiple-target-one-disease. From a molecular/systematic level, this explains why the herbs within a concoction could mutually enhance pharmacological synergy on a disease. Conclusions. The present work provides a new strategy not only for the understanding of pharmacological synergy in herbal medicine, but also for the rational discovery of potent drug/herb combinations that are individually subtherapeutic.

  9. [Non-pharmacological and psychocorporal approaches to manage treatment-induced pain].

    Science.gov (United States)

    Thibault-Wanquet, Pascale

    2010-10-01

    Although healthcare workers always strive to cause the least amount of pain possible when carrying out treatment, interest in the prevention of treatment-induced pain is recent. Thereby, a certain number of non-pharmacological methods to prevent and manage treatment-related pain have proved effective in this field.

  10. Stuttering Treatment Research 1970-2005: II. Systematic Review Incorporating Trial Quality Assessment of Pharmacological Approaches

    Science.gov (United States)

    Bothe, Anne K.; Davidow, Jason H.; Bramlett, Robin E.; Franic, Duska M.; Ingham, Roger J.

    2006-01-01

    Purpose: To complete a systematic review, incorporating trial quality assessment, of published research about pharmacological treatments for stuttering. Goals included the identification of treatment recommendations and research needs based on the available high-quality evidence. Method: Multiple readers reviewed 31 articles published between 1970…

  11. Dissection of Nod factor signalling in legumes: cell biology, mutants and pharmacological approaches

    NARCIS (Netherlands)

    Esseling, J.J.; Emons, A.M.C.

    2004-01-01

    Nodulation factors (NFs) are lipochito-oligosaccharide signal molecules excreted by soil-living rhizobia. These molecules elicit a range of responses in the legume roots, with which the bacteria can live in symbiosis. In this review we focus on the genetic, pharmacological and cell biological approa

  12. PRESENTING CLINICAL-PHARMACOLOGY AND THERAPEUTICS - A PROBLEM-BASED APPROACH FOR CHOOSING AND PRESCRIBING DRUGS

    NARCIS (Netherlands)

    DEVRIES, TPGM

    1993-01-01

    As a guide to the rational choice and prescribing of drugs a normative (ideal) problem-solving model has been developed. This model combines medical problem solving and decision analysis, practical medical aspects, and pharmacological facts and basic principles. It consists of a set of actions or st

  13. Incidence and risk factors for cervical lesions in patients with rheumatoid arthritis under the current pharmacologic treatment paradigm.

    Science.gov (United States)

    Kaito, Takashi; Ohshima, Shirou; Fujiwara, Hiroyasu; Makino, Takahiro; Yonenobu, Kazuo; Yoshikawa, Hideki

    2017-07-01

    To elucidate the incidence and risk factors for cervical lesions in patients with rheumatic arthritis (RA) under the current pharmacologic treatment paradigm. Of patients with RA onset after 2000, 151 who introduced biologic agents (BAs) because of high disease activity and underwent cervical radiography more than 5 years after onset were included. Incidence of those with cervical lesions and predictors of cervical lesions were analyzed. Mean disease duration was 8.5 years. The radiographic definitions of cervical lesions were as follows: atlantoaxial subluxation (AAS), atlantodental interval >3 mm; vertical subluxation (VS), Ranawat value 2 mm. Radiographic evaluation indicated AAS in 43 cases (28%), VS in 10 (7%), and SS in 6 (4%). The incidence of those with any cervical lesion was 32% (48/151). Univariate analysis showed that disease duration, time from onset to BA use, and onset before 2005 were significant predictors of cervical lesions, while multivariate regression analysis showed that disease duration and Steinbrocker stage were predictors. The incidence of cervical lesions in patients with RA onset after 2000 was still high (32%). In addition, disease duration and Steinbrocker stage were predictors of cervical lesions.

  14. 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.

  15. 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.

  16. Applying Theoretical Approach for Predicting the Selective Calcium Channel Blockers Pharmacological Parameter by Biopartitioning Micellar Chromatography

    Institute of Scientific and Technical Information of China (English)

    WANG Su-Min; YANG Geng-Liang; LI Zhi-Wei; LIU Hai-Yan; GUO Hui-Juan

    2006-01-01

    The usefulness of biopartitioning micellar chromatography (BMC) for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model (an LD50 model) and the second order polynomial models (apparent bioavailability model) have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.

  17. The opinion of undergraduate medical students on current curriculum and teaching methodology of pharmacology in four medical colleges of India: a questionnaire based study

    OpenAIRE

    Manoj Kumar Saurabh; Jitendra Agrawal

    2015-01-01

    Background: The objective of current study was to obtain an opinion from 2nd professional year passed medical students on current curriculum, teaching methodology and importance of pharmacology subject and to identify the area of improvement. Methods: A set questionnaire was distributed among randomly distributed to 2nd year passed 100 undergraduate (UG) students to each of four medical colleges. They were instructed to tick out the best possible option of each question on the basis of the...

  18. A pharmacological screening approach for discovery of neuroprotective compounds in ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Simret Beraki

    Full Text Available With the availability and ease of small molecule production and design continuing to improve, robust, high-throughput methods for screening are increasingly necessary to find pharmacologically relevant compounds amongst the masses of potential candidates. Here, we demonstrate that a primary oxygen glucose deprivation assay in primary cortical neurons followed by secondary assays (i.e. post-treatment protocol in organotypic hippocampal slice cultures and cortical neurons can be used as a robust screen to identify neuroprotective compounds with potential therapeutic efficacy. In our screen about 50% of the compounds in a library of pharmacologically active compounds displayed some degree of neuroprotective activity if tested in a pre-treatment toxicity assay but just a few of these compounds, including Carbenoxolone, remained active when tested in a post-treatment protocol. When further examined, Carbenoxolone also led to a significant reduction in infarction size and neuronal damage in the ischemic penumbra when administered six hours post middle cerebral artery occlusion in rats. Pharmacological testing of Carbenoxolone-related compounds, acting by inhibition of 11-β-hydroxysteroid dehydrogenase-1 (11β-HSD1, gave rise to similarly potent in vivo neuroprotection. This indicates that the increase of intracellular glucocorticoid levels mediated by 11β-HSD1 may be involved in the mechanism that exacerbates ischemic neuronal cell death, and inhibiting this enzyme could have potential therapeutic value for neuroprotective therapies in ischemic stroke and other neurodegenerative disorders associated with neuronal injury.

  19. 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

  20. Awareness and Practices of Non-Pharmacological Approaches for Management of Hypertension in a Geriatric Population

    Directory of Open Access Journals (Sweden)

    Debalina Sahoo

    2014-06-01

    Full Text Available Background: There is an increase in the prevalence of hypertension all over the world, including India. Hypertension can be initially managed with non-pharmacological measures. This study aims to assess the knowledge of non-pharmacological measures to control hypertension and its application in a geriatric hypertensive population. Methods: The study was conducted at the Department of Physiology, SVU, Vadodara, India. A total 110 hypertensive patients were included in the study and a non-validated survey was conducted to examine knowledge of non-pharmacological measures to control hypertension in this group of patients. Frequencies, percentages, means and standard deviations were calculated and reported. Results: Only 10% of the respondents knew the normal values for blood pressure. Approximately 38% of the subjects did not measure their blood pressure regularly. A total of 24% subjects knew that body weight has a correlation with hypertension. About 27% said that there was no correlation between salt intake and hypertension, and 88% of the study population did not carry out any form of physical activity. Conclusion: Hypertension can be controlled by life style modifications such as exercise, weight management and a healthy diet. Public health and education measures targeting hypertensive population need to be taken to decrease the risk factors for cardiovascular diseases and, therefore, improve people's health and quality of life.

  1. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

    NARCIS (Netherlands)

    M. Kreuter (Michael); F. Bonella (Francesco); M.S. Wijsenbeek (Marlies); T.M. Maher (Toby M.); P. Spagnolo (Paolo)

    2015-01-01

    textabstractIdiopathic pulmonary fibrosis (IPF) is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid

  2. Synthetic approaches, structure activity relationship and biological applications for pharmacologically attractive pyrazole/pyrazoline-thiazolidine-based hybrids.

    Science.gov (United States)

    Havrylyuk, Dmytro; Roman, Olexandra; Lesyk, Roman

    2016-05-04

    The features of the chemistry of 4-thiazolidinone and pyrazole/pyrazolines as pharmacologically attractive scaffolds were described in a number of reviews in which the main approaches to the synthesis of mentioned heterocycles and their biological activity were analyzed. However, the pyrazole/pyrazoline-thiazolidine-based hybrids as biologically active compounds is poorly discussed in the context of pharmacophore hybrid approach. Therefore, the purpose of this review is to summarize the data about the synthesis and modification of heterocyclic systems with thiazolidine and pyrazoline or pyrazole fragments in molecules as promising objects of modern bioorganic and medicinal chemistry. The description of biological activity was focused on SAR analysis and mechanistic insights of mentioned hybrids.

  3. Cancer of the cervix: current management and new approaches.

    Science.gov (United States)

    Shivnani, Anand T; Rimel, B J; Schink, Julian; Small, William

    2006-11-01

    This article summarizes the current management of patients with newly diagnosed cervical cancer. The topics range from the management of early-stage disease to the phase III randomized studies that have established the current standard of care for patients with locally advanced cancer of the cervix. New approaches to combined-modality therapy with the goal of improving outcomes and decreasing complications are also described.

  4. Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi‐MPS Integration

    National Research Council Canada - National Science Library

    Yu, J; Cilfone, NA; Large, EM; Sarkar, U; Wishnok, JS; Tannenbaum, SR; Hughes, DJ; Lauffenburger, DA; Griffith, LG; Stokes, CL; Cirit, M

    2015-01-01

    Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm...

  5. Echinococcus granulosus tegumental enzymes as in vitro markers of pharmacological damage: a biochemical and molecular approach.

    Science.gov (United States)

    Cumino, Andrea C; Nicolao, M Celeste; Loos, Julia A; Denegri, Guillermo; Elissondo, M Celina

    2012-12-01

    Cystic echinococcosis is a chronic, complex, and neglected disease. Novel therapeutical tools are needed to optimize human treatment. A number of compounds have been investigated, either using in vitro cultured parasites and/or applying in vivo rodent models. Although some of these compounds showed promising activities in vitro, and to some extent also in the rodent models, they have not been translated into clinical applications. Membrane enzyme activities in culture supernatants of treated protoscoleces with calcium modulator drugs and anthelmintic drugs were measured and provided an indication of compound efficacy. This work describes for the first time the detection of alkaline phosphatase, gamma-glutamyl-transpeptidase and acetylcholinesterase activities in supernatants of in vitro treated Echinococcus granulosus protoscoleces. Marked differences on the enzymatic activities in supernatants from drug treated cultures were detected. We demonstrated that those genes that show the highest degree of conservation when compared to orthologs, are constitutively and highly expressed in protoscoleces and metacestodes. Due to high sensibility and the lack of activity in supernatants of intact protoscoleces, gamma-glutamyl-transpeptidase is proposed as the ideal viability marker during in vitro pharmacological studies against E. granulosus protoscoleces.

  6. Current approaches for detection of carcinoma in situ testis

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Olesen, Inge A; Jørgensen, Niels

    2007-01-01

    of carcinoma in situ (CIS). This review describes current possible approaches for the detection of CIS. At present, an open testicular biopsy is the only definitive way of establishing the presence of CIS. The tissue section should be of an adequate size, be properly fixed, and evaluation be supported...

  7. 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.

  8. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

    Science.gov (United States)

    García-Pardo, María Pilar; Roger-Sanchez, Concepción; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María Asunción

    2016-06-15

    Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C (PKC) family (including PKMζ), cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target mammalian target of Rapamycin (mTOR), cyclin-dependent kinase 5 (Cdk5), heat-shock proteins (Hsp) and other enzymes and proteins. Research suggests that drugs of abuse induce dependence and addiction by modifying the signalling pathways that involve these memory-related protein kinases, and supports the idea that drug addiction is an excessive aberrant learning disorder in which the maladaptive memory of drug-associated cues maintains compulsive drug use and contributes to relapse. Moreover, the studies we review offer new pharmacological strategies to treat opiate and cocaine dependence based on the manipulation of these protein kinases. In particular, disruption of reconsolidation of drug-related memories may have a high therapeutic value in the treatment of drug addiction.

  9. Resins and gums in historical iatrosophia texts from Cyprus - a botanical and medico-pharmacological approach

    Directory of Open Access Journals (Sweden)

    Andreas eLardos

    2011-07-01

    Full Text Available 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 analyse 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.

  10. Do pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery?

    Science.gov (United States)

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2008-06-01

    In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of G-signalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.

  11. 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.

  12. LIMITATIONS OF CURRENT APPROACHES FOR THE TREATMENT OF ACROMEGALY.

    Science.gov (United States)

    Shanik, Michael H

    2016-02-01

    Acromegaly is a rare disease characterized by hypersecretion of growth hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients with acromegaly have an increased risk of mortality and progressive worsening of comorbidities. Surgery, medical therapy, and radiotherapy are currently available treatment approaches for patients with acromegaly, with overall therapeutic goals of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size, improving comorbidities, and minimizing mortality risk. Although surgery can lead to biochemical remission in some patients with acromegaly, many patients will continue to have uncontrolled disease and require additional treatment. We reviewed recently published reports and present a summary of the safety and efficacy of current treatment modalities for patients with acromegaly. A substantial proportion of patients who receive medical therapy or radiotherapy will have persistently elevated GH and/or IGF-1. Because of the serious health consequences of continued elevation of GH and IGF-1, there is a need to improve therapeutic approaches to optimize biochemical control, particularly in high-need patient populations for whom current treatment options provide limited benefit. This review discusses current treatment options for patients with acromegaly, limitations associated with each treatment approach, and areas within the current treatment algorithm, as well as patient populations for which improved therapeutic options are needed. Novel agents in development were also highlighted, which have the potential to improve management of patients with uncontrolled or persistent acromegaly.

  13. Multi-target pharmacology: Possibilities and limitations of the skeleton key approach from a medicinal chemist perspective

    Directory of Open Access Journals (Sweden)

    Alan eTalevi

    2015-09-01

    Full Text Available Multi-target drugs have raised considerable interest in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance issues. Prospective drug repositioning to treat comorbid conditions is an additional, overlooked application of multi-target ligands. While medicinal chemists usually rely on some version of the lock and key paradigm to design novel therapeutics, modern pharmacology has recognized that the long-term effects of a given drug on a biological system may depend not only on the specific ligand-target recognition events but also on the influence of the chronic administration of a drug on the cell gene signature. The design of multi-target agents also poses challenging restrictions on the either the topology or flexibility of the candidate drugs which are briefly discussed in the present article. Finally, computational strategies to approach the identification of novel multi-target agents are overviewed.

  14. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

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    Sai Vikram Vemula

    2016-04-01

    Full Text Available Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.

  15. A Social Semiotic Approach to Textbook Analysis: The Construction of the Discourses of Pharmacology

    Science.gov (United States)

    Weiss, Rachel; Archer, Arlene

    2014-01-01

    This article takes a multimodal social semiotic approach to analysing educational textbooks. We are interested in the ways in which educational textbooks contribute to designing our social futures by constructing both the student and the discipline in a particular manner. While a textbook's primary purpose is to provide the reader with knowledge…

  16. A Social Semiotic Approach to Textbook Analysis: The Construction of the Discourses of Pharmacology

    Science.gov (United States)

    Weiss, Rachel; Archer, Arlene

    2014-01-01

    This article takes a multimodal social semiotic approach to analysing educational textbooks. We are interested in the ways in which educational textbooks contribute to designing our social futures by constructing both the student and the discipline in a particular manner. While a textbook's primary purpose is to provide the reader with knowledge…

  17. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Science.gov (United States)

    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. PMID:24216993

  18. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Kosei, E-mail: andokercgv@gmail.com [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Heymann, Marie-Françoise [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France); Stresing, Verena [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Nantes University Hospital, Nantes 44035 (France); Mori, Kanji [Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192 (Japan); Rédini, Françoise; Heymann, Dominique [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France)

    2013-05-24

    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.

  19. Chiral lagrangian approach to exchange vector currents in nuclei

    CERN Document Server

    Park, T S; Rho, M; Park, Tae Sun; Min, Dong Pil; Rho, Mannque

    1995-01-01

    Exchange vector currents are calculated up to one-loop order (corresponding to next-to-next-to-leading order) in chiral perturbation theory. As an illustration of the power of the approach, we apply the formalism to the classic nuclear process n+p\\rightarrow d +\\gamma at thermal energy. The exchange current correction comes out to be (4.5 \\pm 0.3) \\% in amplitude giving a predicted cross section \\sigma= (334\\pm 3)\\ {\\mbox mb} in excellent agreement with the experimental value (334.2\\pm 0.5)\\ {\\mbox mb}. Together with the axial charge transitions computed previously, this result provides a strong support for the power of chiral Lagrangians in nuclear physics. As a by-product of our results, we suggest an open problem in the application of chiral Lagrangian approach to nuclear processes that has to do with giving a physical meaning to the short-range correlations that play an important role in nuclei.

  20. Sleep and Children with Cerebral Palsy: A Review of Current Evidence and Environmental Non-Pharmacological Interventions

    Directory of Open Access Journals (Sweden)

    Risha Dutt

    2015-02-01

    Full Text Available Between 23%–46% of children with cerebral palsy experience sleep problems. Many of the sensory-motor and cognitive features of cerebral palsy (such as immobility, pain, and seizures act as predisposing factors for sleep problems in this population. This paper presents the background related to the etiology and consequences of sleep problems in children with cerebral palsy. The relationship between pain and sleep is emphasized, as the risk of pain is highly prevalent in children with cerebral palsy. The review concludes with a discussion of the evidence-base for environmental non-pharmacological interventions based on light, temperature, sound and bedding to promote sleep for children with cerebral palsy.

  1. Current nutritional approaches in managing autism spectrum disorder: A review.

    Science.gov (United States)

    Cekici, Hande; Sanlier, Nevin

    2017-08-01

    The link between nutrition and autism spectrum disorder (ASD), which is a complex developmental disorder manifesting itself in significant delays or deviation in interaction and communication, has provided a fresh point of view and signals that nutrition may have a role in the aetiology of ASD, as well as play an active role in treatment by alleviating symptoms. In this review study aimed at evaluating, with scientific and concrete proof, the current medical nutrition implementations on ASD, existing medical nutrition therapies have been addressed and their effects on ASD symptoms have been discussed in light of current research. We reviewed articles regarding the medical nutritional therapy of autism on current nutritional approaches selected from PubMed, Science Direct, EBSCO, and databases about autism and nutrition. The research put forward that in individuals with ASD, while gluten-free/casein-free and ketogenic diets, camel milk, curcumin, probiotics, and fermentable foods can play a role in alleviating ASD symptoms, consumption of sugar, additives, pesticides, genetically modified organisms, inorganic processed foods, and hard-to-digest starches may aggravate symptoms. Further prospective controlled trials with large sample sizes are needed before recommendations can be made regarding the ideal ASD diet. This review emphasizes the value of identifying current nutritional approaches specific to individuals with ASD and integrating their effects on symptoms to the conversation and presents suggestions for future research designed to identify medical nutrition therapies targeting this population to better understand the link between ASD and nutrition.

  2. 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.

  3. A Comparison of Multimodal Analgesic Approaches in Institutional ERAS Protocols for Colorectal Surgery: Pharmacological Agents.

    Science.gov (United States)

    Helander, Erik M; Webb, Michael P; Bias, Meghan; Whang, Edward E; Kaye, Alan D; Urman, Richard D

    2017-07-25

    Enhanced recovery after surgery (ERAS(®)) protocols are the cornerstone of improved recovery after colorectal surgery. Their implementation leads to reduced morbidity and shorter hospital stays while attenuating the surgical stress response. Multimodal analgesia is an important part of ERAS protocols. We compared and contrasted protocols from 15 institutions to test our hypothesis that there is a fundamental consensus among them. ERAS protocols for open and laparoscopic colorectal surgery were compared from 15 different healthcare facilities. We examined each institution's approach to multimodal analgesia related to the use of oral and intravenous analgesics. Preoperative, intraoperative, and postoperative management was examined. All but three protocols used preoperative multimodal analgesics, with acetaminophen, celecoxib, and gabapentin being the most common. Intraoperative recommendations included the use of ketamine, lidocaine, magnesium, and ketorolac. Some protocols advocated for the use of opiates, while others aimed to minimize total opioid dose. In the postoperative period, the three most utilized agents were acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. There were many similarities and some significant differences among ERAS protocols examined. Acetaminophen was the most widely used nonopioid agent and along with NSAIDs offers a benefit with respect to postoperative analgesia, opioid-sparing effects, earlier ambulation, and reduction in postoperative ileus. Gabapentin was widely used as it may reduce opioid consumption within the first 24 hours postoperatively. Lidocaine infusion was recommended if there were contraindications to or failure of epidural anesthesia. Ketamine is frequently recommended due to its analgesic, antihyperalgesic, antiallodynic, and antitolerance properties. Differences in approaches may be due to both institutional- and provider-level factors.

  4. 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.

  5. Personalized medicine and treatment approaches in hypertension: current perspectives

    Directory of Open Access Journals (Sweden)

    Byrd JB

    2016-04-01

    Full Text Available James Brian Byrd Division of Cardiovascular Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA Abstract: In the US, hypertension affects one in three adults. Current guideline-based treatment of hypertension involves little diagnostic testing. A more personalized approach to the treatment of hypertension might be of use. Several methods of personalized treatment have been proposed and vetted to varying degrees. The purpose of this narrative review is to discuss the rationale for personalized therapy in hypertension, barriers to its development and implementation, some influential examples of proposed personalization measures, and a view of future efforts. Keywords: hypertension, blood pressure, personalized medicine

  6. Electrostatic discharge current linear approach and circuit design method

    Energy Technology Data Exchange (ETDEWEB)

    Katsivelis, P. K.; Fotis, G. P.; Gonos, I. F.; Koussiouris, T. G.; Stathopulos, I. A. [School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zographou 157 80, Athens (Greece)

    2010-11-15

    The electrostatic discharge (ESD) 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. (authors)

  7. 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.

  8. Non-pharmacological treatment of chronic widespread musculoskeletal pain.

    Science.gov (United States)

    Hassett, Afton L; Williams, David A

    2011-04-01

    Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed.

  9. [Pharmacological treatment of hyperinflation].

    Science.gov (United States)

    Devillier, P; Roche, N

    2009-06-01

    Introduction Lung hyperinflation leads to breathlessness, limitation in exercise capacity and tolerance, and impaired quality of life. Thus, it is important to target this key and characteristic feature of COPD. Current knowledge Available pharmacological approaches rely mainly on bronchodilators, in particular beta2 agonists and anticholinergic agents. These treatments act through the reduction of expiratory airflow limitation. However, changes in classical indices of airflow obstruction do not accurately predict effects on hyperinflation and symptoms. The decrease in operating lung volumes (as reflected by inspiratory capacity or functional residual capacity) at rest and during exercise is one of the mechanisms by which these treatments improve quality of life and maybe also decrease the impact of exacerbations. The effect of beta2 agonists on hyperinflation might be amplified by concurrent treatment with inhaled corticosteroids. Perspectives The effect of new treatments targeting airways inflammation on hyperinflation remains to be explored. Conclusions Measuring the reduction in the degree of lung hyperinflation allows a better understanding of the symptomatic effect of COPD pharmacological treatments.

  10. 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.

  11. 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.

  12. Kindling: a pharmacological approach.

    Science.gov (United States)

    Wasterlain, C G; Morin, A M; Jonec, V

    1982-01-01

    Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.

  13. Modulating Endogenous Electric Currents in Human Corneal Wounds—A Novel Approach of Bioelectric Stimulation Without Electrodes

    Science.gov (United States)

    Reid, Brian; Graue-Hernandez, Enrique O.; Mannis, Mark J.; Zhao, Min

    2011-01-01

    Purpose To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Methods Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Results Unwounded cornea had small outward currents (0.07 μA/cm2). Wounding increased the current more than 5 fold (0.41 μA/cm2). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Conclusions Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients. PMID:21099404

  14. 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...

  15. Investigational pharmacology for low back pain.

    Science.gov (United States)

    Bhandary, Avinash K; Chimes, Gary P; Malanga, Gerard A

    2010-09-06

    Review and reinterpretation of existing literature. This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development. While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.

  16. New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): rationale, pharmacology and evidence for potential therapeutic value.

    Science.gov (United States)

    Ford, John W; Milnes, James T

    2008-08-01

    There is a clear unmet medical need for new pharmacologic therapies for the treatment of atrial fibrillation (AF) with improved efficacy and safety. This article reviews the development of new and novel Kv1.5/ultra-rapid delayed-rectifier current (I Kur) inhibitors and presents evidence that Kv1.5 modulation provides an atrial-selective mechanism for treating AF. Academia and industry have invested heavily in Kv1.5 (>500 scientific publications and >50 patents published since 1993); however, to realize the full value of this therapeutic drug target, clinical efficacy and safety data are required for a selective Kv1.5 modulator. The reward for demonstrating clinical efficacy and safety in a pivotal Phase 3 trial, on regulatory approval, is "first in class" status.

  17. 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.

  18. 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.

  19. Cancer-induced alterations of NK-mediated target recognition: current and investigational pharmacological strategies aiming at restoring NK-mediated anti-tumor activity

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    Anne-Sophie eChretien

    2014-03-01

    Full Text Available Despite evidence of cancer immune-surveillance, which plays a key role in tumor rejection, cancer cells can escape immune recognition through different mechanisms. Thus, evasion to NK cell mediated anti-tumor activity is commonly described and is mediated by various mechanisms, mainly cancer cell-induced down regulation of NK activating receptors (NCRs, NKG2D, DNAM-1 and CD16 as well as up regulation of inhibitory receptors (KIRs, NKG2A. Alterations of NK cells lead to an impaired recognition of tumor cells as well as a decreased ability to interact with immune cells. Alternatively, cancer cells down-regulate expression of ligands for NK cell activating receptors and up-regulate expression of the ligands for inhibitory receptors. A better knowledge of the extent and the mechanisms of these defects will allow developing pharmacological strategies to restore NK cell ability to recognize and lyse tumor cells. Combining conventional chemotherapy and immune modulation is a promising approach likely to improve clinical outcome in diverse neoplastic malignancies. Here, we overview experimental approaches as well as strategies already available in the clinics that restore NK cell functionality. Yet successful cancer therapies based on the manipulation of NK cell already have shown efficacy in the context of hematologic malignancies. Additionally, the ability of cytotoxic agents to increase susceptibility of tumors to NK cell lysis has been studied and may require improvement to maximize this effect. More recently, new strategies were developed to specifically restore NK cell phenotype or to stimulate NK cell functions. Overall, pharmacological immune modulation trends to be integrated in therapeutic strategies and should improve antitumor effects of conventional cancer therapy.

  20. Gastrointestinal Pharmacology.

    Science.gov (United States)

    Saps, Miguel; Miranda, Adrian

    2017-02-25

    There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was beneficial in the treatment of FAPDs in children. There are conflicting data regarding amitriptyline. While one small study found a significant benefit in quality of life compared with placebo, a large multicenter study found no benefit compared with placebo. The antidepressant, citalopram, failed to meet the primary outcomes in intention-to-treat and per-protocol analysis. Rifaximin has been shown to be efficacious in the treatment of adults with IBS. Those findings differ from studies in children where no benefit was found compared to placebo. To date, there are no placebo-controlled trials published on the use of linaclotide or lubiprostone in children. Alpha 2 delta ligands such as gabapentin and pregabalin are sometimes used in the care of this group of children, but no clinical trials are available in children with FAPDs. Similarly, novel drugs that have been approved for the care of irritable bowel with diarrhea in adults such as eluxadoline have yet to be studied in children.

  1. Public Economy versus Planned Economy. Current Approaches and Problems

    Directory of Open Access Journals (Sweden)

    Ani Matei

    2006-03-01

    Full Text Available he present paper proposes a review of the current object and problems facing the public economy. For the past decade and a half, public economy has clearly come back in the attention of the research interests of specialists from the Central and Eastern European countries. Among these, the scientific research encompassed by the public economy area interrelates with the international trends. At a closer look, public economy appears to be a science, particularly interdisciplinary, with sociological, political, econometrical or systemic approaches possible to prevail. To continue, the author makes reference to four pillars of the public economy: optimum, welfare, social choice and economic justice that allow different approaches to develop. A science branch, equally theoretical and practical, public economy will stress its connections with the economic and mathematic modeling, systemic analysis or sociological and political research. Still, seve¬ral problems in public economy remain open. These concentrate on the public interest, intervention and decision. Conceptualization, understanding and description of the mechanisms that allow the operationalisation may form the basis for further developments on both theoretical and practical level. A clear distinction in order to justify the title of this article needs to be made. Public economy is not to be confused with planning economy. The state remains but one of the producers and delivery agents of public goods and services.

  2. Public Economy versus Planned Economy. Current Approaches and Problems

    Directory of Open Access Journals (Sweden)

    Ani Matei

    2006-01-01

    Full Text Available The present paper proposes a review of the current object and problems facing the public economy. For the past decade and a half, public economy has clearly come back in the attention of the research interests of specialists from the Central and Eastern European countries. Among these, the scientific research encompassed by the public economy area interrelates with the international trends. At a closer look, public economy appears to be a science, particularly interdisciplinary, with sociological, political, econometrical or systemic approaches possible to prevail. To continue, the author makes reference to four pillars of the public economy: optimum, welfare, social choice and economic justice that allow different approaches to develop. A science branch, equally theoretical and practical, public economy will stress its connections with the economic and mathematic modeling, systemic analysis or sociological and political research. Still, seve¬ral problems in public economy remain open. These concentrate on the public interest, intervention and decision. Conceptualization, understanding and description of the mechanisms that allow the operationalisation may form the basis for further developments on both theoretical and practical level. A clear distinction in order to justify the title of this article needs to be made. Public economy is not to be confused with planning economy. The state remains but one of the producers and delivery agents of public goods and services.

  3. Know your current I(h: interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.

    Directory of Open Access Journals (Sweden)

    Michele Migliore

    Full Text Available The non-specific, hyperpolarization activated, I(h current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K(+ current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling I(h actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on I(h channel is able to explain virtually all experimental findings on I(h up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by I(h.

  4. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology.

    Science.gov (United States)

    Sáez-Briones, P; Hernández, A

    2013-09-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, "Ecstasy") is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an "open mind state", may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

  5. Pharmacological treatment of trigeminal neuralgia.

    Science.gov (United States)

    Di Stefano, Giulia; Truini, Andrea

    2017-10-01

    Unique among the different neuropathic pain conditions, trigeminal neuralgia frequently has an excellent response to some selected drugs, which, on the other hand, often entail disabling side effects. Physicians should be therefore acquainted with the management of these drugs and the few alternative options. Areas covered: This article, based on a systematic literature review, describes the pharmacological options, and indicates the future perspectives for treating trigeminal neuralgia. The article therefore provides current, evidence-based knowledge about the pharmacological treatment of trigeminal neuralgia, and suggests a practical approach to the various drugs, including starting dose, titration and side effects. Expert commentary: Carbamazepine and oxcarbazepine are the reference standard drugs for treating patients with trigeminal neuralgia. They are effective in most patients. The undesired effects however cause withdrawal from treatment or a dosage reduction to an insufficient level in many patients. Sodium channel blockers selective for the sodium channel 1.7 (Nav1.7) receptor, currently under development, might be an alternative, better-tolerated pharmacological option in the next future.

  6. A network pharmacology approach to discover active compounds and action mechanisms of San-Cao Granule for treatment of liver fibrosis

    Science.gov (United States)

    Wei, Shizhang; Niu, Ming; Wang, Jian; Wang, Jiabo; Su, Haibin; Luo, Shengqiang; Zhang, Xiaomei; Guo, Yanlei; Liu, Liping; Liu, Fengqun; Zhao, Qingguo; Chen, Hongge; Xiao, Xiaohe; Zhao, Pan; Zhao, Yanling

    2016-01-01

    Ethnopharmacological relevance San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis. Materials and methods In this study, a “compound–target–disease” network was constructed by combining the SCG-specific and liver fibrosis–specific target proteins with protein–protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA). Results This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-β1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-β1/Smad pathway. Conclusion SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas. PMID:26929602

  7. 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.

  8. 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.

  9. Healthspan Pharmacology.

    Science.gov (United States)

    Jafari, Mahtab

    2015-12-01

    The main goal of this paper is to present the case for shifting the focus of research on aging and anti-aging from lifespan pharmacology to what I like to call healthspan pharmacology, in which the desired outcome is the extension of healthy years of life rather than lifespan alone. Lifespan could be influenced by both genetic and epigenetic factors, but a long lifespan may not be a good indicator of an optimal healthspan. Without improving healthspan, prolonging longevity would have enormous negative socioeconomic outcomes for humans. Therefore, the goal of aging and anti-aging research should be to add healthy years to life and not merely to increase the chronological age. This article summarizes and compares two categories of pharmacologically induced lifespan extension studies in animal model systems from the last two decades-those reporting the effects of pharmacological interventions on lifespan extension alone versus others that include their effects on both lifespan and healthspan in the analysis. The conclusion is that the extrapolation of pharmacological results from animal studies to humans is likely to be more relevant when both lifespan and healthspan extension properties of pharmacological intervention are taken into account.

  10. Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach.

    Science.gov (United States)

    Sanna, Giovanni; Bertolaccini, Maria Laura; Khamashta, Munther A

    2008-01-01

    The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their

  11. CURRENT APPROACHES TO UNIVERSAL VACCINE AGAINST INFLUENZA VIRUS

    Directory of Open Access Journals (Sweden)

    I. B. Esmagambetov

    2016-01-01

    Full Text Available Influenza is a seasonal infectious disease widespread across the globe. In Russia the share of influenza and other acute respiratory viral infections account for up to 90% of all infectious diseases. Scientific and reasonable method of influenza prevention is vaccination. However, traditional current influenza vaccines can’t induce protection against various virus strains that differ substantially in terms of their antigenic structure, and thus require periodic updates to its immunogenic components. In addition, there is the risk of a pandemic caused by an entirely new antigen in relation to variants of influenza virus A. Attempts to improve on traditional approaches to vaccination have focused primarily on improving production technologies and to increase immunogenicity of vaccines. Therefore, the urgent task is the creation of vaccines able to induce immune response a broad spectrum against different influenza virus strains and human strains of avian influenza, also can cause disease in humans. Protective effect of universal vaccine should be the induction of integrated immune response, based on the formulation of cross-reactive antibodies and T cells. The development of such universal vaccine could remove the need for periodical strain composition update of existing vaccines and, accor dingly, will be able to give the vaccine manufacturer itself, production planning regardless of epidemic seasons. Currently, the most widely studied antigens as key components of flu vaccines are proteins M2 and NP as well as the hemagglutinin of influenza virus. This review summarizes and lists some data of domestic and foreign research on a universal influenza virus vaccine.

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

    Directory of Open Access Journals (Sweden)

    Cecilia Beatrice Chighizola

    2015-01-01

    Full Text Available 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.

  13. 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.

  14. 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.

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

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    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.

  16. Current Approach to the Evaluation and Management of Microscopic Colitis.

    Science.gov (United States)

    Cotter, Thomas G; Pardi, Darrell S

    2017-02-01

    Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients' quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis. Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0-24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment. The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.

  17. Current Approaches and Future Trends to Promote Tendon Repair.

    Science.gov (United States)

    Morais, D S; Torres, J; Guedes, R M; Lopes, M A

    2015-09-01

    Tendons are composed by extracellular collagen fibres arranged in regular arrays and are responsible to transmit tensile forces from a muscle to a bone. Due to their poor healing ability, in some cases tendons injuries are debilitating impairments that affect life quality among adult population worldwide. In the last years, attending to the social and economic concern associated to the high prevalence of tendons injuries and the limited success of the available current treatments, several scaffolds have been developed. Some of these scaffolds are intended to be used as graft-augmentation devices and others to fully replace a damaged tendon. The synthetic ones present superior mechanical characteristics compared to biological scaffolds. However, attending to the specific tendons physiology, even the synthetic scaffolds still don´t present the ideal mechanical properties to accomplish a complete and long-term functional tissue repair. Therefore, to enhance tendogenesis when using a tendon engineering approach, several methodologies have been developed to associate with scaffolds, including surface modification and cell seeding.

  18. Current approaches for the treatment of autoimmune hemolytic anemia.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Rodríguez-Martínez, Marisol; Gómez-de-León, Andrés; Tarín-Arzaga, Luz; Gómez-Almaguer, David

    2013-10-01

    Autoimmune hemolytic anemia (AIHA) is an infrequent group of diseases defined by autoantibody mediated red blood cell destruction. Correct diagnosis and classification of this condition are essential to provide appropriate treatment. AIHA is divided into warm and cold types according to the characteristics of the autoantibody involved and by the presence of an underlying or associated disorder into primary and secondary AIHA. Due to its low frequency, treatment for AIHA is largely based on small prospective trials, case series, and empirical observations. This review describes in detail the different treatment approaches for autoimmune hemolytic anemia. Warm antibody type AIHA should be treated with steroids, to which most patients respond, although relapse can occur and maintenance doses are frequently required. Splenectomy is an effective second line treatment and can provide long-term remission without medication. Rituximab is a useful alternative for steroid refractory patients, those requiring high maintenance doses and unfavorable candidates for surgery. Promising therapeutic modifications with this monoclonal antibody are emerging including drug combinations, lower doses, and long-term use. Primary cold agglutinin disease has been recognized as having a lymphoproliferative monoclonal origin. It is unresponsive to both steroids and splenectomy. Rituximab is currently the best therapeutic alternative for this condition, and several treatment regimens are available with variable responses.

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

    Energy Technology Data Exchange (ETDEWEB)

    Joglekar, Siddharth B. [Musculoskeletal Oncology, Mayo Clinic, Rochester, MN55905 (United States); Rose, Peter S.; Sim, Franklin, E-mail: sim.franklin@mayo.edu [Department of Orthopedics, Mayo Clinic, 200 1st ST SW, Rochester, MN 55905 (United States); Okuno, Scott [Department of Oncology, Mayo Clinic, Rochester, MN55905 (United States); Petersen, Ivy [Department of Radiation Oncology, Mayo Clinic, Rochester, MN55905 (United States)

    2011-08-08

    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.

  20. Investigation of the therapeutic effectiveness of active components in Sini decoction by a comprehensive GC/LC-MS based metabolomics and network pharmacology approaches.

    Science.gov (United States)

    Chen, Si; Wu, Si; Li, Wuhong; Chen, Xiaofei; Dong, Xin; Tan, Guangguo; Zhang, Hai; Hong, Zhanying; Zhu, Zhenyu; Chai, Yifeng

    2014-12-01

    As a classical formula, Sini decoction (SND) has been fully proved to be clinically effective in treating doxorubicin (DOX)-induced cardiomyopathy. Current chemomics and pharmacology proved that the total alkaloids (TA), total gingerols (TG), total flavones and total saponins (TFS) are the major active ingredients of Aconitum carmichaelii, Zingiber officinale and Glycyrrhiza uralensis in SND respectively. Our animal experiments in this study demonstrated that the above active ingredients (TAGFS) were more effective than formulas formed by any one or two of the three individual components and nearly the same as SND. However, very little is known about the action mechanisms of TAGFS. Thus, this study aimed to use for the first time the combination of GC/LC-MS based metabolomics and network pharmacology for solving this problem. By metabolomics, it was found that TAGFS worked by regulating six primary pathways. Then, network pharmacology was applied to search for specific targets. 17 potential cardiovascular related targets were found through molecular docking, 11 of which were identified by references, which demonstrated the therapeutic effectiveness of TAGFS using network pharmacology. Among these targets, four targets, including phosphoinositide 3-kinase gamma, insulin receptor, ornithine aminotransferase and glucokinase, were involved in the TAGFS regulated pathways. Moreover, phosphoinositide 3-kinase gamma, insulin receptor and glucokinase were proved to be targets of active components in SND. In addition, our data indicated TA as the principal ingredient in the SND formula, whereas TG and TFS served as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae with the combination use of metabolomics and network pharmacology may be a good strategy.

  1. 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 dru

  2. 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

  3. 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 dru

  4. Robotic surgery for gastric tumor: current status and new approaches.

    Science.gov (United States)

    Lim, Seung Hyun; Lee, Hae Min; Son, Taeil; Hyung, Woo Jin; Kim, Hyoung-Il

    2016-01-01

    Surgical techniques have evolved tremendously over this past century. To maximize the efficacy and minimize the invasiveness of laparoscopic surgery, researchers have sought to implement wider application of robotics. Nevertheless, both optimism without sound evidence and fear of new technology obscure the appropriate uses of robotic surgery. In the present review, we attempted to provide a balanced perspective on the current state of robotic gastrectomy, outlining evidence and opportunities for the use thereof. Although evidence is limited, the use of robotics is feasible for gastric cancer surgery, and less than 10 cases of robotic surgery are needed to become proficient therein. Compared to the clinical impact of laparoscopy on gastric cancer surgery, the additional benefits of robotic surgery to patients seem to be limited. Despite additional costs and longer surgeries, robotic surgery reportedly does not offer surgical outcomes superior to those for laparoscopic surgery, according to a recent multicenter study. Meanwhile, however, our in-depth review of retrospective and prospective reports revealed that robots could expand the indications of minimally invasive gastrectomy for patients requiring total gastrectomy and D2 lymph node dissection. Moreover, we found that robotic gastrectomy is associated with a higher number of retrieved lymph nodes, less bleeding, fewer complications, and shorter hospital stay, compared to laparoscopic gastrectomy. Accordingly, new surgical approaches using advanced technologies, such as near infrared detectors, the Tilepro(®) multi-input display, dual consoles, and the Single-Site(®) system, are under investigation. In conclusion, measuring the additional benefits of robotic over laparoscopic surgery would be difficult and clinically insignificant. Thus, developing new surgical procedures that extend the benefits of conventional laparoscopic surgery to patients in whom minimally invasive surgery would not be possible is

  5. Diagnostic approach and current treatment options in childhood vasculitis.

    Science.gov (United States)

    Barut, Kenan; Şahin, Sezgin; Adroviç, Amra; Kasapçopur, Özgür

    2015-12-01

    All inflammatory changes in the vessel wall are defined as vasculitis. Pediatric vasculitis may present with different clinical findings. Although Henoch-Schönlein purpura which is the most common pediatric vasculitis generally recovers spontaneously, it should be monitorized closely because of the risk of renal failure. Although Kawasaki disease is easy to diagnose with its classical findings, the diagnosis may be delayed in case of incomplete Kawasaki disease. Kawasaki disease should be considered especially in infants in case of prolonged fever even if the criteria are not fully met and intravenous immunoglobulin treatment should be administered without delay in order to prevent development of coronary artery aneurism. Reaction at the site of administration of Bacillus Calmette-Guerin (BCG) vaccine may be observed as commonly as cervical lymphadenopathy in Kawasaki disease and may be used as a valuable finding in suspicious cases. Although anti-neutrophil cytoplasmic antibody-associated vasculitides are rare in children, renal involvement is more common and progression is more severe compared to adults. Hence, efficient and aggressive treatment is required. Takayasu's arteritis is observed commonly in young adult women and rarely in adolescent girls. Therefore, a careful physical examination and blood pressure measurement should be performed in addition to a detailed history in daily practice. In children with unexplained neurological findings, cerebral vasculitis should be considered in the absence of other systemic vasculitides and necessary radiological investigations should be performed in this regard. This review will provide an insight into the understanding of pediatric vasculitis, current diagnostic approaches and prognosis by the aid of new studies.

  6. Robotic surgery for gastric tumor: current status and new approaches

    Science.gov (United States)

    Lim, Seung Hyun; Lee, Hae Min; Son, Taeil; Hyung, Woo Jin

    2016-01-01

    Surgical techniques have evolved tremendously over this past century. To maximize the efficacy and minimize the invasiveness of laparoscopic surgery, researchers have sought to implement wider application of robotics. Nevertheless, both optimism without sound evidence and fear of new technology obscure the appropriate uses of robotic surgery. In the present review, we attempted to provide a balanced perspective on the current state of robotic gastrectomy, outlining evidence and opportunities for the use thereof. Although evidence is limited, the use of robotics is feasible for gastric cancer surgery, and less than 10 cases of robotic surgery are needed to become proficient therein. Compared to the clinical impact of laparoscopy on gastric cancer surgery, the additional benefits of robotic surgery to patients seem to be limited. Despite additional costs and longer surgeries, robotic surgery reportedly does not offer surgical outcomes superior to those for laparoscopic surgery, according to a recent multicenter study. Meanwhile, however, our in-depth review of retrospective and prospective reports revealed that robots could expand the indications of minimally invasive gastrectomy for patients requiring total gastrectomy and D2 lymph node dissection. Moreover, we found that robotic gastrectomy is associated with a higher number of retrieved lymph nodes, less bleeding, fewer complications, and shorter hospital stay, compared to laparoscopic gastrectomy. Accordingly, new surgical approaches using advanced technologies, such as near infrared detectors, the Tilepro® multi-input display, dual consoles, and the Single-Site® system, are under investigation. In conclusion, measuring the additional benefits of robotic over laparoscopic surgery would be difficult and clinically insignificant. Thus, developing new surgical procedures that extend the benefits of conventional laparoscopic surgery to patients in whom minimally invasive surgery would not be possible is necessary

  7. 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

  8. UNDERGRADUATE MBBS AND BDS STUDENTS’ OPINION BASED SURVEY ON CURRENT TEACHING PRACTICES IN PHARMACOLOGY AND CHANGES RECOMMENDED FOR BETTERMENT OF THE SAME

    Directory of Open Access Journals (Sweden)

    Mohammed Waseem

    2014-12-01

    Full Text Available CONTEXT: Pharmacology is one of the most fundamental subjects in the field of medicine and a good grasp of this subject is vital for any clinical practitioner. The teaching of pharmacology in medical and dental colleges of India has evolved from mere didactic lectures to audio-visual aid based lectures and computer based learning. Evolution of teaching methods is an on-going process and a docent needs proper feedback from the pupils regarding their opinion on what is satisfactory and what needs improvement. AIMS: By way of this survey-based study we aim to grasp the MBBS and BDS students’ opinion regarding the teaching practices in pharmacology and changes recommended for the betterment of the same. METHODS AND MATERIALS: After obtaining due approval of the Institutional Ethics Committee, the study was conducted amongst 2nd year exam going MBBS and BDS students of M R Medical College and S Nijalingappa Dental College, Gulbarga, Karnataka in the Department of Pharmacology M R Medical College. An exhaustive questionnaire based survey was prepared of 17 questions with choices ranging from 3-8 different options. RESULTS AND CONCLUSION: The result of our study favours the need for pharmacology as a subject to be more clinically oriented as well as being technologically sound. The students overall have a positive outlook of pharmacology (53% and consider lectures as the most appropriate and helpful teaching method (62%. Introduction of group discussion is one change that is warranted by students overwhelmingly (41%, followed by introduction of clinical pharmacology exercises (31%. A vast majority of the students (70% found the lectures in pharmacology to be interesting and want them to be more clinically oriented. The importance of pharmacology in clinical decision making is well understood by the majority of students and they aim to act in that behest. Also, we find that computer based learning is a new and important tool coming up in the arsenal

  9. 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.

  10. Beyond (eco)design: current approaches to sustainable packaging design

    OpenAIRE

    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 marketing reasons. This is a rather guild-based approach that, if taken to extremes, would lead to complete elimination of packaging, or at most a quintessential brown paper bag. In industry reality thoug...

  11. 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.

  12. Current migraine management – patient acceptability and future approaches

    Directory of Open Access Journals (Sweden)

    Jean Schoenen

    2008-10-01

    Full Text Available Arnaud Fumal, Jean SchoenenDepartments of Neurology and Functional Neuroanatomy, Headache Research Unit, University of Liège, BelgiumAbstract: Despite its high prevalence and individual as well as societal burden, migraine remains underdiagnosed and undertreated. In recent years, the options for the management of migraine patients have greatly expanded. A number of drugs belonging to various pharmacological classes and deliverable by several routes are now available both for the acute and the preventive treatments of migraine. Nevertheless, disability and satisfaction remain low in many subjects because treatments are not accessible, not optimized, not effective, or simply not tolerated. There is thus still considerable room for better education, for more efficient therapies and for greater support from national health systems. In spite of useful internationally accepted guidelines, anti-migraine treatment has to be individually tailored to each patient taking into account the migraine subtype, the ensuing disability, the patient’s previous history and present expectations, and the co-morbid disorders. In this article we will summarize the phenotypic presentations of migraine and review recommendations for acute and preventive treatment, highlighting recent advances which are relevant for clinical practice in terms of both diagnosis and management.Keywords: migraine, disability, acute treatment, preventive treatment, management

  13. A Network Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Ge-Gen-Qin-Lian Decoction for Treatment of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Huiying Li

    2014-01-01

    Full Text Available Traditional Chinese medicine (TCM herbal formulae can be valuable therapeutic strategies and drug discovery resources. However, the active ingredients and action mechanisms of most TCM formulae remain unclear. Therefore, the identification of potent ingredients and their actions is a major challenge in TCM research. In this study, we used a network pharmacology approach we previously developed to help determine the potential antidiabetic ingredients from the traditional Ge-Gen-Qin-Lian decoction (GGQLD formula. We predicted the target profiles of all available GGQLD ingredients to infer the active ingredients by clustering the target profile of ingredients with FDA-approved antidiabetic drugs. We also applied network target analysis to evaluate the links between herbal ingredients and pharmacological actions to help explain the action mechanisms of GGQLD. According to the predicted results, we confirmed that a novel antidiabetic ingredient from Puerariae Lobatae radix (Ge-Gen, 4-Hydroxymephenytoin, increased the insulin secretion in RIN-5F cells and improved insulin resistance in 3T3-L1 adipocytes. The network pharmacology strategy used here provided a powerful means for identifying bioactive ingredients and mechanisms of action for TCM herbal formulae, including Ge-Gen-Qin-Lian decoction.

  14. [Clinical report on pharmacological treatment of autism].

    Science.gov (United States)

    Thivierge, J

    1998-01-01

    This article reviews the pharmacology of autism and briefly overviews its use, history and novelties. "Autism" does not refer to any pathophysiology currently known. And no drug or class of drugs can cure this illness which includes many. Before using drugs, efficient in relieving symptoms, it is important to consider the potential benefit of behavioral approaches. Developments in research give hope that drugs will cure or prevent this brain illness.

  15. 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 marketi

  16. 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

  17. Review of the History and Current Status of Cell-Transplant Approaches for the Management of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mary J. Eaton

    2012-01-01

    Full Text Available Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant or replacement for current pharmacological treatments, cell therapy is a likely near future clinical tool for improved health care.

  18. Neurocognitive and Social Cognitive Approaches for Improving Functional Outcome in Early Psychosis: Theoretical Considerations and Current State of Evidence

    Directory of Open Access Journals (Sweden)

    Cali F. Bartholomeusz

    2012-01-01

    Full Text Available Improving functional outcome, in addition to alleviating psychotic symptoms, is now a major treatment objective in schizophrenia research. Given the large body of evidence suggesting pharmacological treatments generally have minimal effects on indices of functioning, research has turned to psychosocial rehabilitation programs. Among these, neurocognitive and social cognitive interventions are at the forefront of this field and are argued to target core deficits inherent to the schizophrenia illness. However, to date, research trials have primarily focused on chronic schizophrenia populations, neglecting the early psychosis groups who are often as severely impaired in social and occupational functioning. This theoretical paper will outline the rationale for investigating adjunctive cognitive-based interventions in the early phases of psychotic illness, critically examine the current approach strategies used in these interventions, and assess the evidence supporting certain training programs for improving functional outcome in early psychosis. Potential pathways for future research will be discussed.

  19. HEADROOM APPROACH TO DEVICE DEVELOPMENT: CURRENT AND FUTURE DIRECTIONS

    OpenAIRE

    Girling, A; Lilford, R; Cole, A; Young, T

    2015-01-01

    OBJECTIVES: The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach. METHODS: Health economic modelling in...

  20. Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis

    Directory of Open Access Journals (Sweden)

    Simone Carradori

    2015-03-01

    Full Text Available Due to the recognized biological role of nitric oxide (NO donating derivatives and of selective inhibitors of specific human carbonic anhydrase isoforms (CA, EC 4.2.1.1, promising compounds having an aromatic/heterocyclic primary sulfonamide and functionalized with NO-releasing moieties have been designed. These bifunctional agents have been tested in vitro and in vivo to assess their dual pharmacological activity. According to the encouraging results they could be proposed for the treatment of angle-open glaucoma, cancer regression and osteoporosis, in which both NO and CA activities are involved.

  1. Current approaches to model extracellular electrical neural microstimulation

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    Sébastien eJoucla

    2014-02-01

    Full Text Available Nowadays, high-density microelectrode arrays provide unprecedented possibilities to precisely activate spatially well-controlled central nervous system (CNS areas. However, this requires optimizing stimulating devices, which in turn requires a good understanding of the effects of microstimulation on cells and tissues. In this context, modeling approaches provide flexible ways to predict the outcome of electrical stimulation in terms of CNS activation. In this paper, we present state-of-the-art modeling methods with sufficient details to allow the reader to rapidly build numerical models of neuronal extracellular microstimulation. These include 1 the computation of the electrical potential field created by the stimulation in the tissue, and 2 the response of a target neuron to this field. Two main approaches are described: First we describe the classical hybrid approach that combines the finite element modeling of the potential field with the calculation of the neuron’s response in a cable equation framework (compartmentalized neuron models. Then, we present a whole finite element approach allows the simultaneous calculation of the extracellular and intracellular potentials, by representing the neuronal membrane with a thin-film approximation. This approach was previously introduced in the frame of neural recording, but has never been implemented to determine the effect of extracellular stimulation on the neural response at a sub-compartment level. Here, we show on an example that the latter modeling scheme can reveal important sub-compartment behavior of the neural membrane that cannot be resolved using the hybrid approach. The goal of this paper is also to describe in detail the practical implementation of these methods to allow the reader to easily build new models using standard software packages. These modeling paradigms, depending on the situation, should help build more efficient high-density neural prostheses for CNS rehabilitation.

  2. The Intertemporal Approach to the Current Account: Evidence for Chile

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    Sergio A. Salas Landeau

    2002-03-01

    Full Text Available This paper studies the existence of "excess" current-account imbalances in Chile in the 1960-1999 period. This phenomenon is modelled using present value tests that allow for variable interest rates and exchange rate fluctuations. Despite its simplicity, most of the observed imbalances in the current account are accounted for by the model. Results suggest that using models where agents behave as forward-looking rational agents, is a valid framework. Moreover, the analysis highlights the rel-evance of variable interest rates and exchange rates. Results also imply that capital controls, that were widely used in the period under study, were not effective.

  3. Current Approaches to the Understanding of Early Infantile Autism.

    Science.gov (United States)

    Rickman, David L.

    This review of the literature provides summaries of the genetic, neurophysiological, and biochemical approaches to understanding autism, with special reference to neuroanatomic, cognitive, and neuropsychological studies of this disorder. Available instruments for the assessment of autism and various treatment alternatives including drug therapy,…

  4. Automatic object recognition: critical issues and current approaches

    Science.gov (United States)

    Sadjadi, Firooz A.

    1991-08-01

    Automatic object recognition, with its diverse applications in numerous fields of science and technology, is permeating many aspects of military and civilian industries. This paper gives an overview of the issues confronting the automatic object recognition field and the approaches being used to address these issues.

  5. Current Approaches to Improving Access to Government Documents.

    Science.gov (United States)

    Turner, Carol; Latta, Ann

    Based on the responses of 77 Association of Research Libraries (ARL) member libraries to a December 1986 survey of 106 ARL libraries (a 73% response rate), this report profiles the current state of bibliographic access to federal publications. Following a brief discussion of survey background and methodology, a summary of survey results indicates…

  6. 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…

  7. 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.

  8. Investigational pharmacology for low back pain

    Directory of Open Access Journals (Sweden)

    Avinash K Bhandary

    2010-09-01

    Full Text Available Avinash K Bhandary1 , Gary P Chimes2, Gerard A Malanga3 1Department of Physical Medicine and Rehabilitation, 2Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3New Jersey Sports Medicine Institute; Overlook Hospital; Mountainside Hospital; Rehabilitation Medicine and Electrodiagnosis, St Michael’s Medical Center; Horizon Healthcare Worker’s Compensation Services, Blue Cross and Blue Shield Worker’s Compensation, Summit, NJ, USAStudy design: Review and reinterpretation of existing literature.Objective: This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development.Results/conclusion: While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.Keywords: low back pain, investigational, pharmacology, drugs

  9. 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

  10. Optogenetic Evocation of Field Inhibitory Postsynaptic Potentials in Hippocampal Slices: A Simple and Reliable Approach for Studying Pharmacological Effects on GABAA and GABAB Receptor-Mediated Neurotransmission

    Directory of Open Access Journals (Sweden)

    Julien eDine

    2014-01-01

    Full Text Available The GABAergic system is the main source of inhibition in the mammalian brain. Consequently, much effort is still made to develop new modulators of GABAergic synaptic transmission. In contrast to glutamatergic postsynaptic potentials (PSPs, accurate monitoring of GABA receptor-mediated PSPs (GABAR-PSPs and their pharmacological modulation in brain tissue invariably requires the use of intracellular recording techniques. However, these techniques are expensive, time- and labor-consuming, and, in case of the frequently employed whole-cell patch-clamp configuration, impact on intracellular ion concentrations, signaling cascades, and pH buffering systems. Here, we describe a novel approach to circumvent these drawbacks. In particular, we demonstrate in mouse hippocampal slices that selective optogenetic activation of interneurons leads to prominent field inhibitory GABAAR- and GABABR-PSPs in area CA1 which are easily and reliably detectable by a single extracellular recording electrode. The field PSPs exhibit typical temporal and pharmacological characteristics, display pronounced paired-pulse depression, and remain stable over many consecutive evocations. Additionally validating the methodological value of this approach, we further show that the neuroactive steroid 5-THDOC (5 µM shifts the inhibitory GABAAR-PSPs towards excitatory ones.

  11. Current Approaches for Management of Postpenetrating Keratoplasty Astigmatism

    Directory of Open Access Journals (Sweden)

    Sepehr Feizi

    2011-01-01

    Full Text Available A successful corneal graft requires both clarity and an acceptable refraction. A clear corneal graft may be an optical failure if high astigmatism limits visual acuity. Intraoperative measures to reduce postkeratoplasty astigmatism include round and central trephination of cornea with an adequate size, appropriate sutures with evenly distributed tension, and perfect graft-host apposition. Suture manipulation has been described for minimising early postoperative astigmatism. If significant astigmatism remains after suture removal, which cannot be corrected by optical means, then further surgical procedures containing relaxing incisions, compression sutures, laser refractive surgery, insertion of intrastromal corneal ring segments, wedge resection, and toric intraocular lens implantation can be performed. When astigmatism cannot be reduced using one or more abovementioned approaches, repeat penetrating keratoplasty should inevitably be considered. However, none of these techniques has emerged as an ideal one, and corneal surgeons may require combining two or more approaches to exploit the maximum advantages.

  12. Modification of Current Feedback Strategies: A Text Synthesis Approach.

    Science.gov (United States)

    1984-03-01

    f c o lorad I Technic Report No. 127 This research was aponsored byiwtut ot Cogniive Science The Air Force Office of Scienlbc Uriverulty of Cooado...SYNTHESIS APPROACH(UA COLORADO ANIA AT BOXLDEN INST OF COONITXE SCIENCE P LANGEB ET AL MAN 84 N6 SIID AORT-408 FS-304 / /0 N EA-1216 OIIATOh E CR E...ADDRESS 10. PROGRAM ELEMENT, PROJECT. TASK AREA & WORK( UNIT NUMIERS Institute of Cognitive Science University of Colorado 61103F Boulder, CO 80309

  13. Current approaches and problems in social crime prevention

    OpenAIRE

    Vuković, Slaviša

    2011-01-01

    In this paper the topic of consideration focuses on current methods and forms of implementation social crime prevention, as well as problems that often arise in practice during its implementation. This is one of the most important areas in crime prevention, which is also known as crime prevention through social development, and often includes legal activities of state and non-state actors aimed at preventing delinquency of children and minors through the weakening and, if possible, eliminatin...

  14. Direct current stimulation : new approach to enhancing heavy oil production

    Energy Technology Data Exchange (ETDEWEB)

    Whittle, J.K. [Electro-Petroleum Inc., Wayne, PA (United States); Hill, D.G. [Southern California Univ., Los Angeles, CA (United States)

    2006-07-01

    The limited recovery of heavy crude oil can be attributed to the high viscosity of the liquids in the oil reservoirs. A viable technology has been lacking for the economic recovery of heavy oil. This paper discussed the advantages of direct current electrical stimulation or electro-enhanced oil recovery (EEOR). The paper outlined the advantages, including data produced from field demonstrations as well as the results of recent laboratory studies. The paper provided a historical and electro-chemical background of EEOR. Field operations that were discussed included electric field maps and a comparison of direct current versus alternating current electrical power. A series of EEOR field demonstrations were presented for the Santa Maria basin in California and the eastern Alberta plains. The paper also discussed produced fluid chemical changes and electro-osmosis and effective permeability. Last, the paper provided a comparison of EEOR to other existing and emerging technologies including steam flood; surfactant flood; co-solvent flood; carbon dioxide flood; and fire flood. It was concluded that the biggest EEOR limitation is its limited field application portfolio. EEOR has produced encouraging field demonstrations to date and has facilitated beneficial chemical changes in the produced fluids. 26 refs., 5 tabs., 10 figs.

  15. Current approaches in evolution: from molecules to cells and organisms.

    Science.gov (United States)

    Thattai, Mukund; Peisajovich, Sergio G

    2014-11-01

    This is an exciting time to be an evolutionary biologist. Indeed, it is difficult to keep up with all the studies that fall under the broad category of "Evolution" since they span species, traits, and scales of organization. This special issue gives a flavor of exciting new approaches in evolutionary biology, but also emphasizes universal themes. The reviews contained here discuss important aspects of molecular evolution at multiple scales, from individual proteins to complex regulatory networks, as well as from unicellular organisms to macroscopic traits in animals. Though the model systems are diverse, the issues addressed are fundamental: the origin of evolutionary novelties, and the forces that drive them to fixation.

  16. [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.

  17. CFTR pharmacology.

    Science.gov (United States)

    Zegarra-Moran, Olga; Galietta, Luis J V

    2017-01-01

    CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and expressed in many types of epithelial cells. CFTR-mediated chloride and bicarbonate secretion play an important role in the respiratory and gastrointestinal systems. Pharmacological modulators of CFTR represent promising drugs for a variety of diseases. In particular, correctors and potentiators may restore the activity of CFTR in cystic fibrosis patients. Potentiators are also potentially useful to improve mucociliary clearance in patients with chronic obstructive pulmonary disease. On the other hand, CFTR inhibitors may be useful to block fluid and electrolyte loss in secretory diarrhea and slow down the progression of polycystic kidney disease.

  18. 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.

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

    Science.gov (United States)

    Celik, Orcun; Türk, Hakan; Cakmak, Ozgur; Budak, Salih; Ekin, Rahmi Gokhan; Keskin, Mehmet Zeynel; Yildiz, Guner; Ilbey, Yusuf Ozlem

    2016-01-14

    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.

  20. Current approach in the diagnosis and management of panuveitis

    Directory of Open Access Journals (Sweden)

    Bansal Reema

    2010-01-01

    Full Text Available Panuveitis is a generalized inflammation of not only the whole of the uveal tract but also involves the retina and vitreous humor. It differs from other anatomical sites of inflammation in terms of causes as well as distribution. The common causes of panuveitis in our population are tuberculosis, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, Behcet′s disease and sarcoidosis. A large number of cases still remain idiopathic. A stepwise approach is essential while evaluating these patients to be able to identify and treat the disease timely and correctly. Ancillary tests can be appropriately applied once the anatomic site of inflammation is identified. An exhaustive approach comprising a full battery of tests is obsolete. Only specific tailored investigations are ordered as suggested by the preliminary clinical and ocular examination. The mainstay of the treatment of uveitis is corticosteroids. Immunosuppressive agents are administered if the inflammation is not adequately controlled with corticosteroids. One of the recent breakthroughs in the treatment of refractory uveitis includes the introduction of immunomodulating drugs: Tumor necrosis factor-alpha antagonist and Interferon-alpha. Vitrectomy has been used in uveitis for over a few decades for diagnostic and therapeutic purposes. When compared to other anatomical sites of inflammation, panuveitis has poor visual outcome due to more widespread inflammation. The side-effects of the chronic treatment that these patients receive cannot be overlooked and should be specifically monitored under the supervision of an internist with special interest in inflammatory diseases.

  1. 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

  2. Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD

    Science.gov (United States)

    Zhao, Peng; Li, Jiansheng; Li, Ya; Tian, Yange; Wang, Yonghua; Zheng, Chunli

    2015-01-01

    Background The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown. Methods In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity. Results The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target–disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo. Conclusion This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD

  3. Current Approaches in Implementing Citizen Science in the Classroom.

    Science.gov (United States)

    Shah, Harsh R; Martinez, Luis R

    2016-03-01

    Citizen science involves a partnership between inexperienced volunteers and trained scientists engaging in research. In addition to its obvious benefit of accelerating data collection, citizen science has an unexplored role in the classroom, from K-12 schools to higher education. With recent studies showing a weakening in scientific competency of American students, incorporating citizen science initiatives in the curriculum provides a means to address deficiencies in a fragmented educational system. The integration of traditional and innovative pedagogical methods to reform our educational system is therefore imperative in order to provide practical experiences in scientific inquiry, critical thinking, and problem solving for school-age individuals. Citizen science can be used to emphasize the recognition and use of systematic approaches to solve problems affecting the community.

  4. Ebola virus vaccines: an overview of current approaches.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Heinz

    2014-04-01

    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.

  5. Cognitive enrichment and welfare: Current approaches and future directions

    Directory of Open Access Journals (Sweden)

    Fay E. Clark

    2017-02-01

    Full Text Available “Cognitive enrichment” is a subset of enrichment that has gained interest from researchers over the past decade, particularly those working in zoos. This review explores the forms of cognitive enrichment that have been attempted for laboratory, farmed and zoo animals with a focus on the latter, including various definitions, aims, and approaches. This review reveals the fundamental theoretical and practical problems associated with cognitive enrichment, leading to recommendations for further research in this field. Critically, more research is needed to elucidate what makes challenges appropriate for certain taxa, acknowledging that individual differences exist. Going forward, we should be prepared to incorporate more computer technology into cognitive tasks, and examine novel welfare indicators such as flow, competence, and agency.

  6. Current Approaches in Implementing Citizen Science in the Classroom

    Directory of Open Access Journals (Sweden)

    Harsh R. Shah

    2015-12-01

    Full Text Available Citizen science involves a partnership between inexperienced volunteers and trained scientists engaging in research. In addition to its obvious benefit of accelerating data collection, citizen science has an unexplored role in the classroom, from K–12 schools to higher education. With recent studies showing a weakening in scientific competency of American students, incorporating citizen science initiatives in the curriculum provides a means to address deficiencies in a fragmented educational system. The integration of traditional and innovative pedagogical methods to reform our educational system is therefore imperative in order to provide practical experiences in scientific inquiry, critical thinking, and problem solving for school-age individuals. Citizen science can be used to emphasize the recognition and use of systematic approaches to solve problems affecting the community.

  7. Current approaches on viral infection: proteomics and functional validations

    Directory of Open Access Journals (Sweden)

    Jie eZheng

    2012-11-01

    Full Text Available Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutation of protein target, real time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.

  8. 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

  9. A systematic review of current and emergent manipulator control approaches

    Science.gov (United States)

    Ajwad, Syed Ali; Iqbal, Jamshed; Ullah, Muhammad Imran; Mehmood, Adeel

    2015-06-01

    Pressing demands of productivity and accuracy in today's robotic applications have highlighted an urge to replace classical control strategies with their modern control counterparts. This recent trend is further justified by the fact that the robotic manipulators have complex nonlinear dynamic structure with uncertain parameters. Highlighting the authors' research achievements in the domain of manipulator design and control, this paper presents a systematic and comprehensive review of the state-of-the-art control techniques that find enormous potential in controlling manipulators to execute cuttingedge applications. In particular, three kinds of strategies, i.e., intelligent proportional-integral-derivative (PID) scheme, robust control and adaptation based approaches, are reviewed. Future trend in the subject area is commented. Open-source simulators to facilitate controller design are also tabulated. With a comprehensive list of references, it is anticipated that the review will act as a firsthand reference for researchers, engineers and industrialinterns to realize the control laws for multi-degree of freedom (DOF) manipulators.

  10. RECURRENT ORAL CANCER: CURRENT AND EMERGING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Sabrina Daniela Silva

    2012-07-01

    Full Text Available Oral cancer cavity (OCC is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

  11. Current Approaches Toward Quantitative Mapping of the Interactome.

    Science.gov (United States)

    Buntru, Alexander; Trepte, Philipp; Klockmeier, Konrad; Schnoegl, Sigrid; Wanker, Erich E

    2016-01-01

    Protein-protein interactions (PPIs) play a key role in many, if not all, cellular processes. Disease is often caused by perturbation of PPIs, as recently indicated by studies of missense mutations. To understand the associations of proteins and to unravel the global picture of PPIs in the cell, different experimental detection techniques for PPIs have been established. Genetic and biochemical methods such as the yeast two-hybrid system or affinity purification-based approaches are well suited to high-throughput, proteome-wide screening and are mainly used to obtain qualitative results. However, they have been criticized for not reflecting the cellular situation or the dynamic nature of PPIs. In this review, we provide an overview of various genetic methods that go beyond qualitative detection and allow quantitative measuring of PPIs in mammalian cells, such as dual luminescence-based co-immunoprecipitation, Förster resonance energy transfer or luminescence-based mammalian interactome mapping with bait control. We discuss the strengths and weaknesses of different techniques and their potential applications in biomedical research.

  12. Current approaches to fine mapping of antigen-antibody interactions.

    Science.gov (United States)

    Abbott, W Mark; Damschroder, Melissa M; Lowe, David C

    2014-08-01

    A number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X-ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA-based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity.

  13. Cytotherapies in multiple myeloma: a complementary approach to current treatments?

    Science.gov (United States)

    Ciavarella, Sabino; Caselli, Anna; Savonarola, Annalisa; Tamma, Antonella Valentina; Tucci, Marco; Silvestris, Franco

    2013-06-01

    Based on their tumor tropism, mesenchymal stem cells (MSCs) have been proposed as carriers of cytotoxic molecules in pioneering strategies of anti-cancer gene therapy. Similar to solid tumors, MSCs, genetically modified to stably express the TNF-related apoptosis-inducing ligand (TRAIL), have been applied to counter-attack multiple myeloma (MM) in vitro and envisioned as a promising strategy for future anti-MM treatments. Accumulating evidence based on the detection of genetic and functional abnormalities in MSCs from MM patients points to the supportive function of MSCs in both the development and progression of MM, driven by chronic interplays with malignant cells within the marrow milieu. In this review, we revisit the function of MSCs in the pathophysiology of MM and explore the pivotal mechanisms of their interaction with myeloma cells. We also discuss the therapeutic significance of novel strategies using TRAIL-engineered MSCs in this cancer model, dissecting their role as new tools for future treatments against MM. A cytotherapy based on TRAIL-engineered MSCs against MM may be successfully combined with either conventional approaches of autologous stem cell transplantation or with novel anti-MM drugs. Intensive preclinical investigations are required to identify the best sources as well as modalities of MSC administration, thus defining the translational suitability of this strategy in the clinical setting.

  14. Current approaches towards quantitative mapping of the interactome

    Directory of Open Access Journals (Sweden)

    Alexander eBuntru

    2016-05-01

    Full Text Available Protein-protein interactions (PPIs play a key role in many, if not all, cellular processes. Disease is often caused by perturbation of PPIs, as recently indicated by studies of missense mutations. To understand the associations of proteins and to unravel the global picture of PPIs in the cell, different experimental detection techniques for PPIs have been established. Genetic and biochemical methods such as the yeast two-hybrid (Y2H system or affinity purification-based approaches are well suited to high-throughput, proteome-wide screening and are mainly used to obtain qualitative results. However, they have been criticized for not reflecting the cellular situation or the dynamic nature of PPIs. In this review, we provide an overview of various genetic methods that go beyond qualitative detection and allow quantitative measuring of PPIs in mammalian cells, such as DULIP, FRET or LUMIER with BACON. We discuss the strengths and weaknesses of different techniques and their potential applications in biomedical research.

  15. Treatment of preeclampsia: current approach and future perspectives.

    Science.gov (United States)

    Berzan, Ecaterina; Doyle, Ross; Brown, Catherine M

    2014-09-01

    Hypertension is the most common medical disorder encountered during pregnancy, occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific disorder that occurs after 20 weeks' gestation, characterized by hypertension and proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension. Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all pregnancies. In low-income and middle-income countries, preeclampsia and eclampsia are associated with 10-15 % of direct maternal deaths. Women who develop preeclampsia in pregnancy are at greater risk of cardiovascular and cerebrovascular events even years after their pregnancies. There is significant progress in the elucidation of the underlying mechanisms and pathophysiology of preeclampsia, although its therapeutics remains challenging; delivery of the fetus is still the definitive treatment. Different international societies have produced recommendations and guidelines for clinicians treating preeclampsia, with an overall goal of improving maternal and fetal outcomes. In this review, we focus on the level of blood pressure at which to commence treatment and the current clinical management strategies available to treat and possibly prevent preeclampsia. We also briefly outline some newer perspectives on management of the disorder.

  16. 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.

  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. Amyotrophic lateral sclerosis: clinical features and current treatment approaches

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-06-01

    Full Text Available Amyotrophic lateral sclerosis also known as Lou Gehring's disease, is the most common motor neuron disease characterized by motor neuron degeneration in the primary cortex, brainstem and spinal cord. This leads to widespread paralysis, respiratory insufficiency and death within an average of 3-5 years from disease onset. Majority of cases is sporadic and only 10% have a family story. One of the most interesting discovery in the field of neurodegeneration in recent years is genetic mutation in the C9orf72 (chromosome 9 open reading frame 72 gene, the most common mutation found to be causative of frontotemporal dementia, amyotrophic lateral sclerosis and concomitant of these two diseases. Currently curative therapy for amyotrophic lateral sclerosis is lacking. To date, one medication, Riluzole, has been proved to prolong survival, approximately 3-5 months, in amyotrophic lateral sclerosis. Researches aim to slow disease progression by targeting known pathophysiological pathways or genetics defects. Only symptomatic care to improve quality of life and survival is suggested. These includes respiratory and nutrition support; dysphagia and gastrostomy management; communication and mobility programs; spasticity prevention; pain medication; management of cognitive dysfunction, depression, mood dysorders (especially apathy, fatigue, sleep disturbance and prevention of deep venous thrombosis. [Archives Medical Review Journal 2015; 24(2.000: 182-194

  19. 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.

  20. Current approaches toward production of secondary plant metabolites

    Directory of Open Access Journals (Sweden)

    Md. Sarfaraj Hussain

    2012-01-01

    Full Text Available Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals.

  1. SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment.

    Science.gov (United States)

    Firinu, Davide; Garcia-Larsen, Vanessa; Manconi, Paolo Emilio; Del Giacco, Stefano R

    2016-06-01

    SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results. To date, the use of anti-TNF-α agents has proved to be an effective alternative to conventional treatment for unresponsive or refractory SAPHO cases. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β, IL-6, and IL-8, involved in inflammation, acute-phase response induction, and chemotaxis. IL-1 inhibition strategies with anakinra have shown efficacy as first and second lines of treatment. In this review, we will describe the main characteristics of biological drugs currently used for SAPHO syndrome. We also describe some of the promising therapeutic effects of ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and anakinra. We discuss the use and impact of the new anti-IL-1 antagonists involved in the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.

  2. A live cell, image-based approach to understanding the enzymology and pharmacology of 2-bromopalmitate and palmitoylation.

    Science.gov (United States)

    Mikic, Ivana; Planey, Sonia; Zhang, Jun; Ceballos, Carolina; Seron, Terri; von Massenbach, Benedikt; Watson, Rachael; Callaway, Scott; McDonough, Patrick M; Price, Jeffrey H; Hunter, Edward; Zacharias, David

    2006-01-01

    The addition of a lipid moiety to a protein increases its hydrophobicity and subsequently its attraction to lipophilic environments like membranes. Indeed most lipid-modified proteins are localized to membranes where they associate with multiprotein signaling complexes. Acylation and prenylation are the two common categories of lipidation. The enzymology and pharmacology of prenylation are well understood but relatively very little is known about palmitoylation, the most common form of acylation. One distinguishing characteristic of palmitoylation is that it is a dynamic modification. To understand more about how palmitoylation is regulated, we fused palmitoylation substrates to fluorescent proteins and reported their subcellular distribution and trafficking. We used automated high-throughput fluorescence microscopy and a specialized computer algorithm to image and measure the fraction of palmitoylation reporter on the plasma membrane versus the cytoplasm. Using this system we determined the residence half-life of palmitate on the dipalmitoyl substrate peptide from GAP43 as well as the EC(50) for 2-bromopalmitate, a common inhibitor of palmitoylation.

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

    Directory of Open Access Journals (Sweden)

    Alain P Algazi

    2010-08-01

    Full Text Available Alain P Algazi1, Christopher W Soon2, Adil I Daud11Department of Medicine, Division of Hematology and Oncology, 2Department of Dermatology, University of California, San Francisco San Francisco, CA, USAAbstract: 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.Keywords: melanoma, resection, immune modulation, small molecule kinase inhibitors, chemotherapy, clinical trials

  4. [Current approaches to explain the virulence of Acinetobacter baumannii].

    Science.gov (United States)

    Aşık, Gülşah

    2011-04-01

    Acinetobacter baumannii which is one of the most frequent nosocomial pathogens, has drawn attention in the last years owing to multi-drug resistant strains. A.baumannii may give rise to nosocomial epidemics especially in intensive care units and may lead to treatment failure due to its increasing antimicrobial resistance. These gram-negative non-fermentative coccobacilli may be encountered also in community associated infections. However, they are frequently isolated in pneumonia, urinary tract infection, bacteremia, meningitis and wound infections that develop in patients hospitalized for serious diseases. Although detailed data about the epidemiology and antimicrobial resistance patterns related to this bacteria exist, relatively limited data is present about the virulence factors and environmental physiology of A.baumannii. The role of some bacterial virulence factors in the pathogenesis of Acinetobacter infections have been enlightened by recent investigations. Among these virulence factors, production of extracellular enzymes with lipolytic and cytolytic activities, outer membrane protein (AbOmpA) with apoptotic effects on epithelial cells, adhesion molecules (fimbria and AbOmpA) that function during attachment to epithelial cells, K1 type capsular structure, type-1 pili and AbOmpA induced biofilm formation, siderophore (acinetobactin) or hemin mediated iron acquisition mechanisms, quorum sensing system that functions by the help of N-acyl homoserine lacton signal molecules and cellular components that enable Acinetobacter species to live under inappropriate environmental conditions like dryness, low temperature, restricted nutritional elements, can be counted. New information about the virulence factors will help better understanding of the adaptive response of A.baumannii in the host setting. This review is focused on the current information about the virulence factors of of A.baumannii.

  5. Pharmacological management of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, J.R.

    1985-01-01

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinical trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.

  6. Social pharmacology: expanding horizons

    OpenAIRE

    Rituparna Maiti; José Luis Alloza

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinic...

  7. Social pharmacology: expanding horizons.

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  8. Social Pharmacology: Expanding horizons

    Directory of Open Access Journals (Sweden)

    Rituparna Maiti

    2014-01-01

    Full Text Available In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  9. Pharmacological management of obesity.

    Science.gov (United States)

    Velazquez, Amanda; Apovian, Caroline M

    2017-04-28

    Current management of obesity includes three main arms: behavioral modification, pharmacologic therapy, and bariatric surgery. Decades prior, the only pharmacological agents available to treat obesity were approved only for short-term use (≤ 12 weeks) by the Food and Drug Administration (FDA). However, in the last several years, the FDA has approved several medications for longer term treatment of obesity. This highlights the important progression that we, as a society, better appreciate now the chronicity and complexity of obesity as a disease. Also, availability of more medication options gives healthcare providers more possibilities to consider in the management of obesity. Medications for obesity can be simply categorized as FDA approved short-term use (diethylproprion, phendimetrazine, benzphetamine, and phentermine) and long-term use (orlistat, phentermine/topiramate ER, lorcaserin, naltrexone/bupropion ER and liraglutide). Additionally, type 2 diabetes (T2DM) is commonly seen in patients with obesity and necessitates consideration of pharmacological options that do not hinder patients' weight loss. Finally, weight-centric prescribing is also an important component to pharmacological management of obesity. It warrants that healthcare providers thoroughly review their patients' medication lists to determine if any of these agents could be contributing to weight gain.

  10. Systems Pharmacology in Small Molecular Drug Discovery.

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-02-18

    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.

  11. Systems Pharmacology in Small Molecular Drug Discovery

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-01-01

    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. PMID:26901192

  12. 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.

  13. Neuropathic pain and pharmacological treatment.

    Science.gov (United States)

    Jongen, Joost L M; Hans, Guy; Benzon, Honorio T; Huygen, Frank; Hartrick, Craig T

    2014-03-01

    Neuropathic pain is a serious chronic condition strongly affecting quality of life, which can be relieved but cannot be cured. Apart from symptomatic management, treatment should focus on the underlying disorder. The estimated prevalence is at least 1% to 5% of the general population. Neuropathic pain is characterized both by spontaneous and evoked pain. A diagnosis of neuropathic pain can usually be established based solely on history and neurological examination. Ancillary investigations may include EMG and computerized tomography/magnetic resonance imaging scans, depending on the localization of the suspected lesion. A limited number of agents, primarily directed at symptom control, are currently approved for use in neuropathic pain. A mechanism-based approach to pharmacological intervention supports the use of polypharmacy in neuropathic pain.

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

    Science.gov (United States)

    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 treatment targets with statins. Therefore, an unmet medical need exists for lipid-lowering drugs with novel mechanisms of action to reach the recommended cholesterol target levels, either by monotherapy or combination therapy. Upregulation of the LDL receptor with squalene synthase inhibitors has shown promising results in animal studies but the clinical development of the lead compound lapaquistat (TAK-475) has recently been discontinued. Ezetimibe combined with statins allowed significantly more patients to reach their LDL-C targets. Other inhibitors of intestinal cholesterol absorption such as disodium ascorbyl phytostanol phosphate (FM-VP4) and bile acid transport inhibitors have shown positive results in early development trials, whereas the prospect of acyl coenzyme A: cholesterol acyltransferase inhibition in cardiovascular prevention is dire. Selective inhibition of messenger RNA (mRNA) by antisense oligonucleotides is a new approach to modify cholesterol levels. The inhibition of apolipoprotein B mRNA is in advanced development and mipomersen sodium (ISIS 301012) has shown striking results in phase II studies both as monotherapy as well as in combination with statins.

  15. Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD

    Directory of Open Access Journals (Sweden)

    Zhao P

    2015-12-01

    of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo. Conclusion: This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD. Keywords: chronic obstructive pulmonary disease, Bufei Jianpi formula, systems pharma­cology

  16. 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

  17. Meson-exchange currents and quasielastic predictions for charged-current neutrino-12C scattering in the superscaling approach

    CERN Document Server

    Megias, G D; Moreno, O; Williamson, C F; Caballero, J A; Gonzalez-Jimenez, R; De Pace, A; Barbaro, M B; Alberico, W M; Nardi, M; Amaro, J E

    2014-01-01

    We evaluate and discuss the impact of meson-exchange currents (MEC) on charged-current quasielastic (QE) neutrino cross sections. We consider the nuclear transverse response arising from 2p-2h states excited by the action of electromagnetic, purely isovector meson-exchange currents in a fully relativistic framework, based on the work by the Torino collaboration [1]. An accurate parametrization of this MEC response as a function of the momentum and energy transfers involved is presented. Results of neutrino-nucleus cross sections using this MEC parametrization together with a recent scaling approach for the 1p-1h contributions (SuSAv2) are compared with experimental data (MiniBooNE, MINERvA, NOMAD and T2K Collaborations).

  18. Pharmacological Augmentation of Psychosocial and Remediation Training Efforts in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Philip D. Harvey

    2017-09-01

    Full Text Available Pharmacological approaches to cognitive enhancement have received considerable attention but have not had considerable success in improving their cognitive and functional targets. Other intervention strategies, such as cognitive remediation therapy (CRT, have been shown to enhance cognitive performance but have not been found to improve functional outcomes without additional psychosocial interventions. Recently, several studies have attempted to enhance the effects of CRT by adding pharmacological interventions to the CRT treatments. In addition, as CRT has been shown to synergistically improve the effects of psychosocial interventions, the combination of pharmacological therapies aimed at cognition and psychosocial interventions may itself provide a promising strategy for improving functional outcomes. This review and commentary examines the current state of interventions combining CRT and psychosocial treatments with pharmacological augmentation. Our focus is on the specific level of effect of the pharmacological intervention, which could be enhancing motivation, training efficiency, or the consolidation of therapeutic gains. Different pharmacological strategies (e.g., stimulants, plasticity-inducing agents, or attentional or alertness enhancers may have the potential to lead to different types of gains when combined with CRT or psychosocial interventions. The relative potential of these different mechanisms for immediate and durable effects is considered.

  19. [Pharmacological treatment of chronic pain].

    Science.gov (United States)

    Willimann, Patrick

    2011-09-01

    The pharmacological treatment of chronic pain differs from acute pain management. In chronic non-cancer pain patients pharmacological treatment is only one element of an interdisciplinary approach. Not pain reduction only but gain in physical and social functioning is mandatory for continuation of therapy. The developpement of a strategy is the most important and difficult step toward an individual and sustained pharmacological pain treatment. Simple practical guidelines can help to find an individual therapeutic straight. Outcome parameters have to be determined. Check-ups for discontinuation of the therapy have to be done periodically. Exact documentation of effect and side effects prevents ungrateful and potential dangerous treatments. The WHO ladder remains the cornerstone of pharmacological pain treatment. Further analgesics as antidepressants and anticonvulsants are important in treatment of neuropathic or mixed pain states. Special considerations have to be done in opioid treatment of non-cancer pain regarding the lack of evidence in long term outcome and possible side effects and risks.

  20. Social Pharmacology: Expanding horizons

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of “social pharmacology” is not covered by the so-called “Phase IV” alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the “life cycle” of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences. PMID:24987168

  1. 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.

  2. Not Another Quiz: An Approach to Engage Today's Students in Meaningful Current Events Discussions

    Science.gov (United States)

    Wright, Leigh L.; Shemberger, Melony; Price, Elizabeth

    2016-01-01

    Journalism professors are concerned with how effectively students understand current news events and engage with mainstream news sources. This essay is based on a survey administered to students in a newswriting course and analyzed the kinds of current news that students followed in weekly assignments designed with a digital, interactive approach.…

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

    Directory of Open Access Journals (Sweden)

    Kamendi Harriet W

    2011-01-01

    Full Text Available Abstract Background 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. Method 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. Results 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. Conclusion 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.

  4. Pharmacology of antiplatelet agents.

    Science.gov (United States)

    Kalra, Kiran; Franzese, Christopher J; Gesheff, Martin G; Lev, Eli I; Pandya, Shachi; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

    2013-12-01

    Pharmacotherapies with agents that inhibit platelet function have proven to be effective in the treatment of acute coronary syndromes, and in the prevention of complications during and after percutaneous coronary intervention. Because of multiple synergetic pathways of platelet activation and their close interplay with coagulation, current treatment strategies are based not only on platelet inhibition, but also on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current strategies can be broadly categorized as anticoagulants, antiplatelet agents, and fibrinolytics. This review focuses on the pharmacology of current antiplatelet therapy primarily targeting the inhibition of the enzyme cyclooxygenase 1, the P2Y12 receptor, the glycoprotein IIb/IIIa receptor, and protease-activated receptor 1.

  5. Pharmacologic treatment of sex offenders with paraphilic disorder.

    Science.gov (United States)

    Garcia, Frederico Duarte; Delavenne, Heloise Garcia; Assumpção, Alessandra de Fátima Almeida; Thibaut, Florence

    2013-05-01

    Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even eliminate deviant sexual behavior in sex offenders with paraphilic disorders. In this article, we will review pharmacological treatment options for sex offenders with paraphilias. Both serotonin selective reuptake inhibitors (SSRIs) and antiandrogen treatments have been used with reported success in decreasing recidivism. SSRIs have been used in mild types of paraphilias and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe sex offenders with paraphilic disorders in order to reduce victimization. Combined pharmacological and psychotherapeutic treatment is associated with better efficacy. Imaging studies may improve the knowledge of paraphilic disorders and the mechanisms of action of current treatments. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of treatments.

  6. 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.

  7. Current pharmacological and phytochemical studies of the plant Alpinia galanga%大高良姜的药理学及植物化学研究综述

    Institute of Scientific and Technical Information of China (English)

    DhirenderKaushik; JyotiYadav; PawanKaushik; DishaSacher; RubyRani

    2011-01-01

    Traditional medicine systems consist of large numbers of plants with medicinal and pharmacological importance and hence represent an invaluable reservoir of new bioactive molecules.Alpinia galanga (family Zingiberaceae) is commonly known as galangal and has been used for its emmenagogue,aphrodisiac,abortifacient,carminative,antipyretic and antiinflammatory qualities and used in the treatment of various diseases such as bronchitis,heart diseases,chronic enteritis,renal calculus,diabetes,rheumatism and kidney disorders.It was reported to contain,among other components,essential oils,tannins,phenol,glycosides,monoterpenes and carbohydrates.In the last few years,new compounds such as gallic acid glycoside,galangoisoflavonoid,β-sitosterol,galangin,alpinin,zerumbone and kampferide have been isolated from various parts of A.galanga.Therefore,the present review is aimed to summarize the information regarding A.galanga concerning the new phytoconstituents and pharmacological uses that have appeared in recent years.%传统医学使用大量具有医用及药用价值的植物治疗疾病,因此是生物活性物质的一个宝库.姜科植物大高良姜通常被用作调经剂、催欲剂、堕胎药、驱风剂、退热剂和抗炎药等,可用于治疗支气管炎、心脏疾病、慢性肠炎、肾结石、糖尿病、风湿病及肾脏疾病.大高良姜含有精油、鞣酸、苯酚、苷类、单萜及糖类等.过去几年,有报道大高良姜各部位提取物中还含有没食子酸、生姜异黄酮、β-谷甾醇、高良姜素、良姜素、花姜酮、山萘素等.本文总结了近年来有关大高良姜的研究中新的植物化学成分及药理学的研究内容.

  8. 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.

  9. Resolution Pharmacology: Opportunities for Therapeutic Innovation in Inflammation.

    Science.gov (United States)

    Perretti, Mauro; Leroy, Xavier; Bland, Elliot J; Montero-Melendez, Trinidad

    2015-11-01

    Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellular mechanisms that are engaged to actively resolve inflammation. The 'resolution of acute inflammation' is enabled by counter-regulatory checkpoints to terminate the inflammatory reaction, promoting healing and repair. It may be possible to harness this knowledge for innovative approaches to the treatment of inflammatory pathologies. Here we discuss current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status. We reason this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, 'resolution pharmacology'.

  10. A frailty model approach for regression analysis of multivariate current status data.

    Science.gov (United States)

    Chen, Man-Hua; Tong, Xingwei; Sun, Jianguo

    2009-11-30

    This paper discusses regression analysis of multivariate current status failure time data (The Statistical Analysis of Interval-censoring Failure Time Data. Springer: New York, 2006), which occur quite often in, for example, tumorigenicity experiments and epidemiologic investigations of the natural history of a disease. For the problem, several marginal approaches have been proposed that model each failure time of interest individually (Biometrics 2000; 56:940-943; Statist. Med. 2002; 21:3715-3726). In this paper, we present a full likelihood approach based on the proportional hazards frailty model. For estimation, an Expectation Maximization (EM) algorithm is developed and simulation studies suggest that the presented approach performs well for practical situations. The approach is applied to a set of bivariate current status data arising from a tumorigenicity experiment.

  11. How to Improve Current Situation of the Communicative Approach in High School EFL Teaching

    Institute of Scientific and Technical Information of China (English)

    张丽芳

    2009-01-01

    The Communicative Approach has been used in EFL teaching of China for years; but still there are some problems centers around it when it is applied in high school English teaching. This paper explores the current situation of the Communicative Approach in Chinese high school EFL teaching by first looking at a simple case study, and then some suggestions are given as to how to improve this situation.

  12. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics

    OpenAIRE

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment...

  13. Longitudinal gradient coils with enhanced radial uniformity in restricted diameter: Single-current and multiple-current approaches

    Science.gov (United States)

    Romero, Javier A.; Domínguez, Gabriela A.; Anoardo, Esteban

    2017-03-01

    An important requirement for a gradient coil is that the uniformity of the generated magnetic field gradient should be maximal within the active volume of the coil. For a cylindrical geometry, the radial uniformity of the gradient turns critic, particularly in cases where the gradient-unit has to be designed to fit into the inner bore of a compact magnet of reduced dimensions, like those typically used in fast-field-cycling NMR. In this paper we present two practical solutions aimed to fulfill this requirement. We propose a matrix-inversion optimization algorithm based on the Biot-Savart law, that using a proper cost function, allows maximizing the uniformity of the gradient and power efficiency. The used methodology and the simulation code were validated in a single-current design, by comparing the computer simulated field map with the experimental data measured in a real prototype. After comparing the obtained results with the target field approach, a multiple-element coil driven by independent current sources is discussed, and a real prototype evaluated. Opposed equispaced independent windings are connected in pairs conforming an arrangement of independent anti-Helmholtz units. This last coil seizes 80% of its radial dimension with a gradient uniformity better than 5%. The design also provides an adaptable region of uniformity along with adjustable coil efficiency.

  14. Nucleic acid drugs: a novel approach

    African Journals Online (AJOL)

    Administrator

    In this way the nucleic acids act as drug for inhibiting gene expression or protein synthesis. This article examines ... The majority of currently employed pharmacological approaches for ..... of antiviral and anticancer in near future. REFERENCE.

  15. A Semiconductor Device Noise Model: A Deterministic Approach to Semiconductor Device Current Noise for Semiclassical Transport

    Science.gov (United States)

    Noaman, B. A.; Korman, C. E.

    2009-04-01

    In this paper, we present a deterministic approach to calculate terminal current noise characteristics in semiconductor devices in the framework of semiclassical transport based on the spherical harmonics of the Boltzmann Transport Equation. The model relies on the solution of the Boltzmann equation in the frequency domain with special initial and boundary conditions. The terminal current fluctuation is directly related to scattering without the additional Langevin noise term added to the calculation. Simulation results are presented for the terminal current spectral density for a 1-D n+nn+ structure due to elastic-acoustic and intervally scattering.

  16. First update of the current evidence for the management of ankylosing spondylitis with non-pharmacological treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis.

    Science.gov (United States)

    van den Berg, Rosaline; Baraliakos, Xenofon; Braun, Jürgen; van der Heijde, Désirée

    2012-08-01

    To perform a systematic literature review as a basis for the update of the Assessment in SpondyloArthritis International Society and European League Against Reumatism (ASAS/EULAR) recommendations for the management of AS with non-pharmacological interventions and non-biologic drugs. The search was performed in PubMed, EMBASE, PEDro and Cochrane between 1 January 2005 and 1 December 2009, and in abstracts of EULAR and ACR meetings (2007-09). Effect sizes for outcomes on pain, disease activity, spinal mobility and physical function and level of evidence were presented. Of 2383 papers, 35 with complete data were included. Physical therapy exercises in various modalities have positive effects on BASFI, BASDAI, pain and mobility function. Various NSAIDs including coxibs improve BASDAI, disease activity and BASFI. No effect of SSZ and MTX on any variable was found. Surgical interventions of the spine and the hip can give excellent results by restoring function. This concise summary of current evidence for non-pharmacological interventions and non-biologic drugs formed the basis for the update of the ASAS/EULAR recommendations for the management of AS.

  17. 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...

  18. Review of Current Status and Research Approaches to Nitrogen Pollution in Farmlands

    Institute of Scientific and Technical Information of China (English)

    NIE Sheng-wei; GAO Wang-sheng; CHEN Yuan-quan; SUI Peng; A Egrinya Eneji

    2009-01-01

    In this paper, the history, current status, and research approaches to nitrogen pollution were reviewed using systems analysis and deductions. The seriousness of N pollution world-wide was highlighted and recommendations were made to address the situation. A new hypothesis based on phytoremediation, which means the use of plants to directly or indirectly degrade or remove contaminats from soil and water, was proposed.

  19. Relevance of animal studies in regulatory toxicology : current approaches and future opportunities

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Feron, V.J.

    1996-01-01

    With rapidly increasing knowledge of toxicological processes, the scientific value and relevance of toxicity studies for risk assessment must be re-evaluated. In this paper, it is proposed that the rigid risk evaluation currently required should be replaced by a more flexible, case-by-case approach,

  20. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

    Directory of Open Access Journals (Sweden)

    Miroslav Radenković

    2013-01-01

    Full Text Available The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

  1. The Metabolism of Anticancer Drugs by the Liver: Current Approaches to the Drug Development Process.

    Science.gov (United States)

    Belka, Mariusz; Bączek, Tomasz

    2015-01-01

    The worldwide scientific community is in agreement that the activities of metabolic enzymes greatly impact the efficacies of anticancer drugs. Elucidation of the influences of these drugs on metabolism, especially that occurring in the liver, appears to be an extremely important step in the development of new anticancer drugs. Considering the continuous need to search for safe and effective chemotherapeutics, studies of the metabolism of new potent drugs are very important and should be included in the modern, innovative drug development pipeline. This article summarizes most of the current metabolic case studies involving anticancer drug development. Firstly, the impacts of diverse metabolic enzymes, particularly cytochrome P450, and the utilities of a few model in vitro enzymatic systems are described. Then, different analytical techniques, with particular emphasis on liquid chromatography- mass spectrometry detection and structural elucidation, are discussed. Finally, some computer-aided strategies for decision making in the drug design process are described. Recent advances in drug development, including microdosing, in vitro-in vivo correlation and pharmacologic audit trail, are also discussed in relation to metabolic studies.

  2. 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

    OpenAIRE

    Haiyu Xu; Yanqiong Zhang; Yun Lei; Xiumei Gao; Huaqiang Zhai; Na Lin; Shihuan Tang; Rixin Liang; Yan Ma; Defeng Li; Yi Zhang; Guangrong Zhu; Hongjun Yang; Luqi Huang

    2014-01-01

    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 ult...

  3. 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.

  4. Pharmacology and therapeutics of bronchodilators.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Calzetta, Luigino; Matera, M Gabriella

    2012-07-01

    Bronchodilators are central in the treatment of of airways disorders. They are the mainstay of the current management of chronic obstructive pulmonary disease (COPD) and are critical in the symptomatic management of asthma, although controversies around the use of these drugs remain. Bronchodilators work through their direct relaxation effect on airway smooth muscle cells. at present, three major classes of bronchodilators, β(2)-adrenoceptor (AR) agonists, muscarinic receptor antagonists, and xanthines are available and can be used individually or in combination. The use of the inhaled route is currently preferred to minimize systemic effects. Fast- and short-acting agents are best used for rescue of symptoms, whereas long-acting agents are best used for maintenance therapy. It has proven difficult to discover novel classes of bronchodilator drugs, although potential new targets are emerging. Consequently, the logical approach has been to improve the existing bronchodilators, although several novel broncholytic classes are under development. An important step in simplifying asthma and COPD management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence. Several once-daily β(2)-AR agonists or ultra-long-acting β(2)-AR-agonists (LABAs), such as indacaterol, olodaterol, and vilanterol, are already in the market or under development for the treatment of COPD and asthma, but current recommendations suggest the use of LABAs only in combination with an inhaled corticosteroid. In addition, some new potentially long-acting antimuscarinic agents, such as glycopyrronium bromide (NVA-237), aclidinium bromide, and umeclidinium bromide (GSK573719), are under development, as well as combinations of several classes of long-acting bronchodilator drugs, in an attempt to simplify treatment

  5. Expanding the reduced-current approach for thermoelectric generators to achieve higher volumetric power density

    DEFF Research Database (Denmark)

    Wijesooriyage, Waruna Dissanayaka; Rosendahl, Lasse

    2015-01-01

    Thermoelectrics are candidate niche electrical generator devices for energy management. At present, scientists are more focused on thermoelectric (TE) material development, but the TE module design procedure is still in a relatively virgin state. One of the most well-known methods is the reduced...... current approach (RCA) for TE module design, where the same current is induced through the p and n legs of the thermoelectric generator (TEG). The current density of each element is manipulated by changing the area of both legs. This technique leads to a TE module architecture based on the most efficient...... configuration of both p and n legs. In the current paper, we apply an extended version of this technique, to show how a TE module with a higher volumetric power density can be designed, compared to the original RCA. Our studies indicate that for some combinations of p and n material properties, optima yielding...

  6. 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.

  7. Efficient non-hydrostatic modelling of 3D wave-induced currents using a subgrid approach

    Science.gov (United States)

    Rijnsdorp, Dirk P.; Smit, Pieter B.; Zijlema, Marcel; Reniers, Ad J. H. M.

    2017-08-01

    Wave-induced currents are an ubiquitous feature in coastal waters that can spread material over the surf zone and the inner shelf. These currents are typically under resolved in non-hydrostatic wave-flow models due to computational constraints. Specifically, the low vertical resolutions adequate to describe the wave dynamics - and required to feasibly compute at the scales of a field site - are too coarse to account for the relevant details of the three-dimensional (3D) flow field. To describe the relevant dynamics of both wave and currents, while retaining a model framework that can be applied at field scales, we propose a two grid approach to solve the governing equations. With this approach, the vertical accelerations and non-hydrostatic pressures are resolved on a relatively coarse vertical grid (which is sufficient to accurately resolve the wave dynamics), whereas the horizontal velocities and turbulent stresses are resolved on a much finer subgrid (of which the resolution is dictated by the vertical scale of the mean flows). This approach ensures that the discrete pressure Poisson equation - the solution of which dominates the computational effort - is evaluated on the coarse grid scale, thereby greatly improving efficiency, while providing a fine vertical resolution to resolve the vertical variation of the mean flow. This work presents the general methodology, and discusses the numerical implementation in the SWASH wave-flow model. Model predictions are compared with observations of three flume experiments to demonstrate that the subgrid approach captures both the nearshore evolution of the waves, and the wave-induced flows like the undertow profile and longshore current. The accuracy of the subgrid predictions is comparable to fully resolved 3D simulations - but at much reduced computational costs. The findings of this work thereby demonstrate that the subgrid approach has the potential to make 3D non-hydrostatic simulations feasible at the scale of a

  8. Traditional Chinese medicine network pharmacology: theory, methodology and application.

    Science.gov (United States)

    Li, Shao; Zhang, Bo

    2013-03-01

    Traditional Chinese medicine (TCM) has a long history of viewing an individual or patient as a system with different statuses, and has accumulated numerous herbal formulae. The holistic philosophy of TCM shares much with the key ideas of emerging network pharmacology and network biology, and meets the requirements of overcoming complex diseases, such as cancer, in a systematic manner. To discover TCM from a systems perspective and at the molecular level, a novel TCM network pharmacology approach was established by updating the research paradigm from the current "one target, one drug" mode to a new "network target, multi-components" mode. Subsequently, a set of TCM network pharmacology methods were created to prioritize disease-associated genes, to predict the target profiles and pharmacological actions of herbal compounds, to reveal drug-gene-disease co-module associations, to screen synergistic multi-compounds from herbal formulae in a high-throughput manner, and to interpret the combinatorial rules and network regulation effects of herbal formulae. The effectiveness of the network-based methods was demonstrated for the discovery of bioactive compounds and for the elucidation of the mechanisms of action of herbal formulae, such as Qing-Luo-Yin and the Liu-Wei-Di-Huang pill. The studies suggest that the TCM network pharmacology approach provides a new research paradigm for translating TCM from an experience-based medicine to an evidence-based medicine system, which will accelerate TCM drug discovery, and also improve current drug discovery strategies. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  9. Current-induced forces in mesoscopic systems: A scattering-matrix approach

    Directory of Open Access Journals (Sweden)

    Niels Bode

    2012-02-01

    Full Text Available Nanoelectromechanical systems are characterized by an intimate connection between electronic and mechanical degrees of freedom. Due to the nanoscopic scale, current flowing through the system noticeably impacts upons the vibrational dynamics of the device, complementing the effect of the vibrational modes on the electronic dynamics. We employ the scattering-matrix approach to quantum transport in order to develop a unified theory of nanoelectromechanical systems out of equilibrium. For a slow mechanical mode the current can be obtained from the Landauer–Büttiker formula in the strictly adiabatic limit. The leading correction to the adiabatic limit reduces to Brouwer’s formula for the current of a quantum pump in the absence of a bias voltage. The principal results of the present paper are the scattering-matrix expressions for the current-induced forces acting on the mechanical degrees of freedom. These forces control the Langevin dynamics of the mechanical modes. Specifically, we derive expressions for the (typically nonconservative mean force, for the (possibly negative damping force, an effective “Lorentz” force that exists even for time-reversal-invariant systems, and the fluctuating Langevin force originating from Nyquist and shot noise of the current flow. We apply our general formalism to several simple models that illustrate the peculiar nature of the current-induced forces. Specifically, we find that in out-of-equilibrium situations the current-induced forces can destabilize the mechanical vibrations and cause limit-cycle dynamics.

  10. 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.

  11. Molecular approaches towards development of purified natural products and their structurally known derivatives as efficient anti-cancer drugs: current trends.

    Science.gov (United States)

    Saha, Santu Kumar; Khuda-Bukhsh, Anisur Rahman

    2013-08-15

    Several natural products and their derivatives, either in purified or structurally identified form, exhibit immense pharmacological and biological properties, some of them showing considerable anticancer potential. Although the molecular mechanisms of action of some of these products are yet to be elucidated, extensive research in this area continues to generate new data that are clinically exploitable. Recent advancement in molecular biology, high throughput screening, biomarker identifications, target selection and genomic approaches have enabled us to understand salient interactions of natural products and their derivatives with cancer cells vis-à-vis normal cells. In this review we highlight the recent approaches and application of innovative technologies made to improve quality as well as efficiency of structurally identified natural products and their derivatives, particularly in small molecular forms capable of being used in "targeted therapies" in oncology. These products preferentially involve multiple mechanistic pathways and overcome chemo-resistance in tumor types with cumulative action. We also mention briefly a few physico-chemical features that compare natural products with drugs in recent natural product discovery approaches. We further report here a few purified natural products as examples that provide molecular interventions in cancer therapeutics to give the reader a glimpse of the current trends of approach for discovering useful anticancer drugs.

  12. Current opinion in Alzheimer's disease therapy by nanotechnology-based approaches.

    Science.gov (United States)

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Perveen, Asma; Ashraf, Ghulam Md

    2017-03-01

    Nanotechnology typically deals with the measuring and modeling of matter at nanometer scale by incorporating the fields of engineering and technology. The most prominent feature of these engineered materials involves their manipulation/modification for imparting new functional properties. The current review covers the most recent findings of Alzheimer's disease (AD) therapeutics based on nanoscience and technology. Current studies involve the application of nanotechnology in developing novel diagnostic and therapeutic tools for neurological disorders. Nanotechnology-based approaches can be exploited for limiting/reversing these diseases for promoting functional regeneration of damaged neurons. These strategies offer neuroprotection by facilitating the delivery of drugs and small molecules more effectively across the blood-brain barrier. Nanotechnology based approaches show promise in improving AD therapeutics. Further replication work on synthesis and surface modification of nanoparticles, longer-term clinical trials, and attempts to increase their impact in treating AD are required.

  13. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics.

    Science.gov (United States)

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

  14. Expectation values of flavor-neutrino currents in field theoretical approach to oscillation problem -- formulation

    CERN Document Server

    Fujii, Kanji; Fujii, Kanji; Shimomura, Takashi

    2004-01-01

    As a possible approach to the neutrino oscillation on the basis of quantum field theory, the expectation values of the flavor-neutrino currents are investigated by employing the finite-time transition matrix in the interaction representation. Such expectation values give us in the simplest form a possible way of treating the neutrino oscillation without recourse to any one flavor-neutrino states. The present paper is devoted to presenting the formulation and the main structures of the relevant expectation values.

  15. Expectation values of flavor-neutrino currents in field theoretical approach to oscillation problem -- formulation

    OpenAIRE

    FUJII, Kanji; Shimomura, Takashi

    2004-01-01

    As a possible approach to the neutrino oscillation on the basis of quantum field theory, the expectation values of the flavor-neutrino currents are investigated by employing the finite-time transition matrix in the interaction representation. Such expectation values give us in the simplest form a possible way of treating the neutrino oscillation without recourse to any one flavor-neutrino states. The present paper is devoted to presenting the formulation and the main structures of the relevan...

  16. An adaptive finite element approach to modelling sediment laden density currents

    Science.gov (United States)

    Parkinson, S.; Hill, J.; Allison, P. A.; Piggott, M. D.

    2012-04-01

    Modelling sediment-laden density currents at real-world scales is a challenging task. Here we present Fluidity, which uses dynamic adaptive re-meshing to reduce computational costs whilst maintaining sufficient resolution where and when it is required. This allows small-scale processes to be captured in large scale simulations. Density currents, also known as gravity or buoyancy currents, occur wherever two fluids with different densities meet. They can occur at scales of up to hundred kilometres in the ocean when continental shelves collapse. This process releases large quantities of sediment into the ocean which increase the bulk density of the fluid to form a density current. These currents can carry sediment hundreds of kilometres, at speeds of up to a hundred kilometres per hour, over the sea bed. They can be tsunamigenic and they have the potential to cause significant damage to submarine infrastructure, such as submarine telecommunications cables or oil and gas infrastructure. They are also a key process for movement of organic material into the depths of the ocean. Due to this, they play an important role in the global carbon cycle on the Earth, forming a significant component of the stratigraphic record, and their deposits can form useful sources of important hydrocarbons. Modelling large scale sediment laden density currents is a very challenging problem. Particles within the current are suspended by turbulence that occurs at length scales that are several orders of magnitude smaller than the size of the current. Models that resolve the vertical structure of the flow require a very large, highly resolved mesh, and substantial computing power to solve. Here, we verify our adaptive model by comparison with a set of laboratory experiments by Gladstone et al. [1998] on the propagation and sediment deposition of bidisperse gravity currents. Comparisons are also made with fixed mesh solutions, and it is shown that accuracy can be maintained with fewer elements

  17. 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

  18. Ionic channel current burst analysis by a machine learning based approach.

    Science.gov (United States)

    Rauch, Giuseppe; Bertolini, Simona; Sacile, Roberto; Giacomini, Mauro; Ruggiero, Carmelina

    2011-09-01

    A new method to analyze single ionic channel current conduction is presented. It is based on an automatic classification by K-means algorithm and on the concept of information entropy. This method is used to study the conductance of multistate ion current jumps induced by tetanus toxin in planar lipid bilayers. A comparison is presented with the widely used Gaussian best fit approach, whose main drawback is the fact that it is based on the manual choice of the base line and of meaningful fragments of current signal. On the contrary, the proposed method is able to automatically process a great amount of information and to remove spurious transitions and multichannels. The number of levels and their amplitudes do not have to be known a priori. In this way the presented method is able to produce a reliable evaluation of the conductance levels and their characteristic parameters in a short time.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Nestor R. Ramos

    2015-04-01

    Full Text Available 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.

  1. Phosphodiesterase inhibitors: history of pharmacology.

    Science.gov (United States)

    Schudt, Christian; Hatzelmann, Armin; Beume, Rolf; Tenor, Hermann

    2011-01-01

    The first pharmacological investigations of phosphodiesterase (PDE) inhibitors were developed with the clinical efficacies of drugs isolated from coffee, cacao and tea but only later their relevant ingredients were identified as xanthines that act as PDE. With its diuretic, inotropic and bronchodilating clinical efficacy, use of theophylline anticipated the clinical goals, which were later approached with the first-generation of weakly selective PDE inhibitors in the period from 1980 to 1990. Pharmacological and clinical research with these early compounds provided a vast pool of information regarding desired and adverse actions - although most of these new drugs had to be discontinued due to severe adverse effects. The pharmacological models for cardiac, vascular and respiratory indications were analysed for their PDE isoenzyme profiles, and when biochemical and molecular biological approaches expanded our knowledge of the PDE superfamily, the purified isoenzymes that were now available opened the door for more systematic studies of inhibitors and for generation of highly selective isoenzyme-specific drugs. The development of simple screening models and clinically relevant indication models reflecting the growing knowledge about pathomechanisms of disease are summarised here for today's successful application of highly selective PDE3, PDE4 and PDE5 inhibitors. The interplay of serendipitous discoveries, the establishment of intelligent pharmacological models and the knowledge gain by research results with new substances is reviewed. The broad efficacies of new substances in vitro, the enormous biodiversity of the PDE isoenzyme family and the sophisticated biochemical pharmacology enabled Viagra to be the first success story in the field of PDE inhibitor drug development, but probably more success stories will follow.

  2. 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.

  3. Principles of safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Authier, S; Curtis, M J

    2008-08-01

    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).

  4. Inibidores da HIV-integrase: potencial abordagem farmacológica para tratamento da AIDS HIV-integrase inhibitors: potential pharmacological approach for AIDS therapy

    Directory of Open Access Journals (Sweden)

    Eduardo Borges de Melo

    2006-06-01

    Full Text Available AIDS has the HIV as its etiological agent. Researches has been done to find new pharmacological agents to be used in therapy, because of problems of resistance and side effects. The HIV-integrase inhibitors are some of those new agents that are being studied. This updating focusses on the fundamental information about HIV and HIV-integrase and the main methods being used to develop these new drugs, with examples for each case.

  5. [Pharmacologic treatment of Asperger syndrome].

    Science.gov (United States)

    Yamada, Satoru

    2007-03-01

    Asperger syndrome is associated with various dysfunctional and problematic behaviors, in addition to the core features of communication and social skills dysfunction that define these conditions. Although there is currently no pharmacologic cure for the core features of Asperger syndrome. This article discusses the various medications for the behavioral symptoms of Asperger syndrome, which include hyperactivity, aggression, tantrums, self-injury, depression, obsession and so on. Methylphenidate, SSRIs, atypical antipsychotics and mood stabilizer were introduced.

  6. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    Science.gov (United States)

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  7. Quark flavour mixing with right-handed currents: an effective theory approach

    CERN Document Server

    Buras, Andrzej J; Isidori, Gino

    2010-01-01

    The impact of right-handed currents in both charged- and neutral-current flavour-violating processes is analysed by means of an effective theory approach. More explicitly, we analyse the structure of dimension-six operators assuming a left-right symmetric flavour group, commuting with an underlying $SU(2)_L \\times SU(2)_R \\times U(1)_{B-L}$ global symmetry, broken only by two Yukawa couplings. The model contains a new unitary matrix controlling flavour-mixing in the right-handed sector. We determine the structure of this matrix by charged-current data, where the tension between inclusive and exclusive determinations of $|V_{ub}|$ can be solved. Having determined the size and the flavour structure of right-handed currents, we investigate how they would manifest themselves in neutral current processes, including particle-antiparticle mixing, $Z\\to b \\bar b$, $B_{s,d}\\to \\mu^+\\mu^-$, $B\\to {Xs,K,K*} \

  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. Person-centred health care: a critical assessment of current and emerging research approaches.

    Science.gov (United States)

    Martin, Carmel M; Félix-Bortolotti, Margot

    2014-12-01

    Person-centred health care is prominent in international health care reforms. A shift to understanding and improving personal care at the point of delivery has generated debates about the nature of the person-centred research agenda. This paper purviews research paradigms that influence current person-centred research approaches and traditions that influence knowledge foundations in the field. It presents a synthesis of the emergent approaches and methodologies and highlights gaps between static academic research and the increasing accessibility of evaluation, informatics and big data from health information systems. Paradigms in health services research range from theoretical to atheoretical, including positivist, interpretive, postmodern and pragmatic. Interpretivist (subjective) and positivist (objectivist) paradigms have been historically polarized. Yet, integrative and pragmatic approaches have emerged. Nevertheless, there is a tendency to reductionism, and to reduce personal experiences to metrics in the positivist paradigm. Integrating personalized information into clinical systems is increasingly driven by the pervasive health information technology, which raises many issues about the asymmetry and uncertainty in the flow of information to support personal health journeys. The flux and uncertainty of knowledge between and within paradigmatic or pragmatic approaches highlights the uncertainty and the 'unorder and disorder' in what is known and what it means. Transdisciplinary, complex adaptive systems theory with multi-ontology sense making provides an overarching framework for making sense of the complex dynamics in research progress. A major challenge to current research paradigms is focus on the individualizing of care and enhancing experiences of persons in health settings. There is an urgent need for person-centred research to address this complex process. A transdisciplinary and complex systems approach provides a sense-making framework. © 2014 John

  10. [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.

  11. Pharmacological treatment of vertigo.

    Science.gov (United States)

    Hain, Timothy C; Uddin, Mohammed

    2003-01-01

    This review discusses the physiology and pharmacological treatment of vertigo and related disorders. Classes of medications useful in the treatment of vertigo include anticholinergics, antihistamines, benzodiazepines, calcium channel antagonists and dopamine receptor antagonists. These medications often have multiple actions. They may modify the intensity of symptoms (e.g. vestibular suppressants) or they may affect the underlying disease process (e.g. calcium channel antagonists in the case of vestibular migraine). Most of these agents, particularly those that are sedating, also have a potential to modulate the rate of compensation for vestibular damage. This consideration has become more relevant in recent years, as vestibular rehabilitation physical therapy is now often recommended in an attempt to promote compensation. Accordingly, therapy of vertigo is optimised when the prescriber has detailed knowledge of the pharmacology of medications being administered as well as the precise actions being sought. There are four broad causes of vertigo, for which specific regimens of drug therapy can be tailored. Otological vertigo includes disorders of the inner ear such as Ménière's disease, vestibular neuritis, benign paroxysmal positional vertigo (BPPV) and bilateral vestibular paresis. In both Ménière's disease and vestibular neuritis, vestibular suppressants such as anticholinergics and benzodiazepines are used. In Ménière's disease, salt restriction and diuretics are used in an attempt to prevent flare-ups. In vestibular neuritis, only brief use of vestibular suppressants is now recommended. Drug treatments are not presently recommended for BPPV and bilateral vestibular paresis, but physical therapy treatment can be very useful in both. Central vertigo includes entities such as vertigo associated with migraine and certain strokes. Prophylactic agents (L-channel calcium channel antagonists, tricyclic antidepressants, beta-blockers) are the mainstay of treatment

  12. Pharmacology for the Psychotherapist.

    Science.gov (United States)

    Goldenberg, Myron Michael

    This book covers those areas of pharmacology that are of importance and interest to the psychotherapist. The 1st chapter introduces the various types of drugs. The 2nd chapter presents an overview of pharmacology and its principles. The 3rd chapter reviews aspects of the human body of importance to understanding the workings of psychotropic drugs.…

  13. Integrating pharmacology and clinical pharmacology in universities.

    Science.gov (United States)

    Buckingham, Julia C

    2012-06-01

    Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery-development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills.

  14. A multi-faceted treatment approach for anterior reconstructions using current ceramics, implants, and adhesive systems.

    Science.gov (United States)

    Hajtó, Jan; Gehringer, Uwe; Ozcan, Mutlu

    2010-01-01

    Of all developments in dental technology, fulfilling the esthetic and functional demands of the patient, especially regarding anterior reconstructions, is still a challenge for both dentists and dental technicians. This becomes more difficult for patients with a previous treatment history that is not ideal. This case presentation demonstrates reconstruction of an anterior zirconia resin-bonded fixed dental prosthesis (RBFDP) for the mandible with a combined approach utilizing veneers for harmonized space distribution on the abutment teeth and an implant-supported zirconia fixed dental prosthesis in the anterior segment of the maxilla. Adhesive cementation of the restorations is also presented in a step-by-step approach based on the current state of the art.

  15. Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses.

    Science.gov (United States)

    Jentsch, Mike C; Van Buel, Erin M; Bosker, Fokko J; Gladkevich, Anatoliy V; Klein, Hans C; Oude Voshaar, Richard C; Ruhé, Eric G; Eisel, Uli L M; Schoevers, Robert A

    2015-01-01

    Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to enable monitoring and prognosis of treatment response. However, currently known biomarkers do not reach sufficient sensitivity and specificity, and often the relation to underlying pathophysiology is unclear. In this review, we evaluate various biomarker approaches in terms of scientific merit and clinical applicability. Finally, we discuss how combined biomarker approaches in both preclinical and clinical studies can help to make the connection between the clinical manifestations of depression and the underlying pathophysiology.

  16. Modelling of eddy-current interaction with cracks in the thin-skin regime. Two approaches

    Energy Technology Data Exchange (ETDEWEB)

    Mastorchio, S. [Electricite de France, 78 - Chatou (France). Research and Development Div.; Harfield, N. [Surrey Univ. (United Kingdom). Dept. of Physics

    1998-02-01

    EDF uses TRIFOU code for eddy current testing modelling. This general electromagnetic code is to be further adapted to Non Destructive Testing applications, not only for nuclear NDT but also in other fields such as aeronautical. This paper compares experimental data for aluminium and steel specimens with two methods of solving the forward problem in the thin-skin regime. The first approach is a 3D Finite Element / Boundary Integral Element method (TRIFOU) developed by EDF/RD Division (France). The second approach is specialized for the treatment of surface cracks in the thin-skin regime developed by the University of Surrey (England). In the thin-skin regime, the electromagnetic skin-depth is small compared with the depth of the crack. Such conditions are common in tests on steels and sometimes on aluminium. (K.A.) 4 refs.

  17. Charged-current neutrino-nucleus reactions within the SuSAv2-MEC approach

    CERN Document Server

    Megias, G D; Barbaro, M B; Caballero, J A; Donnelly, T W; Simo, I Ruiz

    2016-01-01

    We present a detailed study of charged-current (CC) neutrino-nucleus reactions in a fully relativis- tic framework and comparisons with recent experiments spanning an energy range from hundreds of MeV up to 100 GeV within the SuperScaling Approach, which is based on the analysis of electron- nucleus scattering data and has been recently improved with the inclusion of Relativistic Mean Field theory effects. We also evaluate and discuss the impact of two-particle two-hole meson-exchange currents (2p-2h MEC) on neutrino-nucleus interactions through the analysis of two-particle two-hole axial and vector contributions to weak response functions in a fully relativistic Fermi gas. The results show a fairly good agreement with experimental data over the whole range of neutrino energies.

  18. Variational approach to low-frequency kinetic-MHD in the current coupling scheme

    CERN Document Server

    Burby, J W

    2016-01-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which is described by a kinetic equation. When the Vlasov description is adopted for the energetic particles, different Vlasov-MHD models have been shown to lack an exact energy balance, which was recently recovered by the introduction of non-inertial force terms in the kinetic equation. These force terms arise from fundamental approaches based on Hamiltonian and variational methods. In this work we apply Hamilton's variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling hybrid schemes, in which energetic particle dynamics are expressed in either guiding-center or gyrocenter coordinates.

  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. Variational approach to low-frequency kinetic-MHD in the current-coupling scheme

    Science.gov (United States)

    Tronci, Cesare; Burby, Joshua

    2016-10-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which is described by a kinetic equation. When the Vlasov description is adopted for the energetic particles, different Vlasov-MHD models have been shown to lack an exact energy balance, unless non-inertial force terms are inserted in the kinetic equation. These force terms arise from fundamental approaches based on Hamiltonian and variational methods. In this work we apply Hamilton's variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling hybrid schemes, in which energetic particle dynamics are expressed in either guiding-center or gyrocenter coordinates. Financial support by the Leverhulme Trust Research Project Grant No. 2014-112 is greatly acknowledged.

  1. 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...

  2. Future Performance Trend Indicators: A Current Value Approach to Human Resources Accounting. Report V: The Value Attribution Process. Technical Report.

    Science.gov (United States)

    Lapointe, Jean B.; And Others

    The development of future performance trend indicators is based on the current value approach to human resource accounting. The value attribution portion of the current value approach is used to estimate the dollar value of observed changes in the state of the human organization. The procedure for value attribution includes: prediction of changes…

  3. Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder.

    Science.gov (United States)

    Choi, Dennis C; Rothbaum, Barbara O; Gerardi, Maryrose; Ressler, Kerry J

    2010-01-01

    Improved efficacy in the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders is urgently needed. Traditional anxiety treatments of hypnosis and psychodynamic therapy may be of some help, but uncontrolled studies lead to inconclusive results on the efficacy of these treatment techniques. There is a larger literature supporting the efficacy of cognitive-behavioral procedures with PTSD, including prolonged exposure therapy, eye movement desensitization and reprocessing, and anxiety management techniques. The cutting-edge technology of virtual reality-based exposure therapy for PTSD is particularly exciting. To further build on effective psychosocial treatments, current pharmacological augmentation approaches to emotional learning are being combined with psychotherapy. In particular, D-cycloserine, a partial NMDA agonist, has shown to be effective in facilitating the exposure/extinction therapy to improve the efficacy of treating anxiety disorders, and may guide the way for new pharmacological enhancements of behavioral therapy.

  4. Preventive pharmacological treatment --an evolving new concept in schizophrenia.

    Science.gov (United States)

    Sabbag, Rony; Levin, Raz; Edelman, Shany; Heresco-Levy, Uriel

    2011-01-01

    Treatment for schizophrenia remains one of the major challenges of modern medicine. The development of innovative pharmacological approaches for this disorder can potentially alleviate tremendous human suffering and revolutionize mental health delivery systems. While current treatment guidelines for schizophrenia refer to the post-psychosis onset phase of illness, presently there is a strong resurgent interest in secondary prevention intervention applied during schizophrenia prodrome. This development stems largely from the recognition that neurobiological deficit processes associated with schizophrenia severity and chronicity are already active by the time clinical onset is recognized. Proposed preventive treatments include presently used medications and experimental compounds that hypothetically may influence ongoing pathophysiological processes earlier in their development. The future establishment of the early recognition and intervention concept in schizophrenia is critically dependent on the outcome of ongoing research assessing the feasibility of prodrome diagnosis, the efficacy of specific medications and the alleviation of the risks associated with early pharmacological treatment.

  5. A review of the current status of endoluminal therapy as a primary approach to obesity management.

    Science.gov (United States)

    Majumder, Shounak; Birk, John

    2013-07-01

    Gastroenterologists are expected to play a pivotal role in the management of the global obesity epidemic in coming years as novel endoscopic approaches become more widely available, safe, and effective. This review focuses on the recent advances in the field of endoluminal therapy as a primary approach to obesity management with the aim of providing the interventional endoscopist an overview of currently available evidence along with an insight into upcoming devices and techniques. The intragastric balloon appears to be safe and effective in the short term, especially as a bridge to bariatric surgery. Although early trials support the safety and feasibility of endoscopic gastroplasty, it is technically demanding and staple-line dehiscence continues to be a problem. Moreover, with ongoing technical innovations, most devices that have been used in published trials are no longer manufactured and results of studies using newer endoscopic suturing systems are currently awaited. The duodenojejunal bypass sleeve mimics the physiology of intestinal bypass and shares the metabolic advantages of intestinal diversion. A high rate of premature device withdrawal has been its major limiting factor. Therapeutic endoscopy may be the next paradigm of bariatric care. Combining restrictive and barrier endoscopic techniques can potentially improve efficacy and should be evaluated in the setting of appropriate clinical trials.

  6. 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.

  7. Quark flavour mixing with right-handed currents: An effective theory approach

    Energy Technology Data Exchange (ETDEWEB)

    Buras, Andrzej J. [Physik-Department, Technische Universitaet Muenchen, James-Franck-Strasse, D-85748 Garching (Germany); TUM Institute for Advanced Study, Technische Universitaet Muenchen, Arcisstrasse 21, D-80333 Muenchen (Germany); Gemmler, Katrin [Physik-Department, Technische Universitaet Muenchen, James-Franck-Strasse, D-85748 Garching (Germany); Isidori, Gino, E-mail: isidori@lnf.infn.i [TUM Institute for Advanced Study, Technische Universitaet Muenchen, Arcisstrasse 21, D-80333 Muenchen (Germany); INFN, Laboratori Nazionali di Frascati, I-00044 Frascati (Italy)

    2011-02-01

    The impact of right-handed currents in both charged- and neutral-current flavour-violating processes is analysed by means of an effective theory approach. More explicitly, we analyse the structure of dimension-six operators assuming a left-right symmetric flavour group, commuting with an underlying SU(2){sub L}xSU(2){sub R}xU(1){sub B-L} global symmetry, broken only by two Yukawa couplings. The model contains a new unitary matrix controlling flavour-mixing in the right-handed sector. We determine the structure of this matrix by charged-current data, where the tension between inclusive and exclusive determinations of {vert_bar}V{sub ub}{vert_bar} can be solved. Having determined the size and the flavour structure of right-handed currents, we investigate how they would manifest themselves in neutral current processes, including particle-antiparticle mixing, Z{yields}bb-bar, B{sub s,d}{yields}{mu}{sup +}{mu}{sup -}, B{yields}{l_brace}X{sub s},K,K{sup *}{r_brace}{nu}{nu}-bar, and K{yields}{pi}{nu}{nu}-bar decays. The possibility to explain a non-standard CP-violating phase in B{sub s} mixing in this context, and the comparison with other predictive new-physics frameworks addressing the same problem, is also discussed. While a large S{sub {psi}{phi}} asymmetry can easily be accommodated, we point out a tension in this framework between {vert_bar}V{sub ub}{vert_bar} and S{sub {psi}}K.

  8. [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.

  9. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer.

    Science.gov (United States)

    Falahi, Fahimeh; van Kruchten, Michel; Martinet, Nadine; Hospers, Geke A P; Rots, Marianne G

    2014-07-29

    DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alterations have been associated with various diseases, including breast cancer. Since aberrant epigenetic modifications are potentially reversible, they might represent targets for breast cancer therapy. Indeed, several drugs have been designed to inhibit epigenetic enzymes (epi-drugs), thereby reversing epigenetic modifications. US Food and Drug Administration approval has been obtained for some epi-drugs for hematological malignancies. However, these drugs have had very modest anti-tumor efficacy in phase I and II clinical trials in breast cancer patients as monotherapy. Therefore, current clinical trials focus on the combination of epi-drugs with other therapies to enhance or restore the sensitivity to such therapies. This approach has yielded some promising results in early phase II trials. The disadvantage of epi-drugs, however, is genome-wide effects, which may cause unwanted upregulation of, for example, pro-metastatic genes. Development of gene-targeted epigenetic modifications (epigenetic editing) in breast cancer can provide a novel approach to prevent such unwanted events. In this context, identification of crucial epigenetic modifications regulating key genes in breast cancer is of critical importance. In this review, we first describe aberrant DNA methylation and histone modifications as two important classes of epigenetic mutations in breast cancer. Then we focus on the preclinical and clinical epigenetic-based therapies currently being explored for breast cancer. Finally, we describe epigenetic editing as a promising new approach for possible applications towards more targeted breast cancer treatment.

  10. Segmentation and Image Analysis of Abnormal Lungs at CT: Current Approaches, Challenges, and Future Trends

    Science.gov (United States)

    Mansoor, Awais; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z.; Folio, Les R.; Udupa, Jayaram K.; Mollura, Daniel J.

    2015-01-01

    The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shape-based, (d) neighboring anatomy–guided, and (e) machine learning–based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. ©RSNA, 2015 PMID:26172351

  11. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.

    Science.gov (United States)

    Christopoulos, Arthur; Changeux, Jean-Pierre; Catterall, William A; Fabbro, Doriano; Burris, Thomas P; Cidlowski, John A; Olsen, Richard W; Peters, John A; Neubig, Richard R; Pin, Jean-Philippe; Sexton, Patrick M; Kenakin, Terry P; Ehlert, Frederick J; Spedding, Michael; Langmead, Christopher J

    2014-10-01

    Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

  12. Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

    Science.gov (United States)

    Pichavant, Christophe; Aartsma-Rus, Annemieke; Clemens, Paula R; Davies, Kay E; Dickson, George; Takeda, Shin'ichi; Wilton, Steve D; Wolff, Jon A; Wooddell, Christine I; Xiao, Xiao; Tremblay, Jacques P

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article. PMID:21468001

  13. Pharmacology of Periodontal Disease.

    Science.gov (United States)

    2014-09-26

    k 7RD-A157 116 PHARMRCOLOGY’ OF PERIODONTAL DISEASE(U) UNIVERSITY OF i/ I HEALTH SCIENCES/CHICAGO MEDICAL SCHOOL DEPT OF I PHARMACOLOGY S F HOFF 24...Region Bethesda, MD 20814-5044 • .RE: Annual Letter Report , ONR Contract #N00014-84-K-0562 "Pharmacology of Periodontal Disease" Dear Capt. Hancock...Annual Letter Report ONR Contract #N00014-84-K-0562 1,! t "Pharmacology of Periodontal Disease" f Steven F. Hoff, Ph.D. (Principal Investigator) A

  14. Advancing pharmacometrics and systems pharmacology.

    Science.gov (United States)

    Waldman, S A; Terzic, A

    2012-11-01

    Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

  15. 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.

  16. Pharmacological Effects of Mangiferin

    Institute of Scientific and Technical Information of China (English)

    WEI Zhi-quan; DENG Jia-gang; YAN Li

    2011-01-01

    Mango leaves have been widely used in the clinical practice for thousands of years in traditional Chinese medicine.Mangiferin,an effective constituent in the mango leaves,has multiple pharmacological actions involved in some basic pathological processes,such as inflammation,oxidative injury,tumor growth,micro-organism infections,metabolic regulations,and immunological regulations.The pharmacological effects of mangiferin from some published data are reviewed in this article.

  17. The pharmacology of psilocybin.

    Science.gov (United States)

    Passie, Torsten; Seifert, Juergen; Schneider, Udo; Emrich, Hinderk M

    2002-10-01

    Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

  18. Current Approach in Surface Plasmons for Thin Film and Wire Array Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Keya Zhou

    2015-07-01

    Full Text Available Surface plasmons, which exist along the interface of a metal and a dielectric, have been proposed as an efficient alternative method for light trapping in solar cells during the past ten years. With unique properties such as superior light scattering, optical trapping, guide mode coupling, near field concentration, and hot-electron generation, metallic nanoparticles or nanostructures can be tailored to a certain geometric design to enhance solar cell conversion efficiency and to reduce the material costs. In this article, we review current approaches on different kinds of solar cells, such as crystalline silicon (c-Si and amorphous silicon (a-Si thin film solar cells, organic solar cells, nanowire array solar cells, and single nanowire solar cells.

  19. Prevention of Overweight and Obesity: How Effective is the Current Public Health Approach

    Directory of Open Access Journals (Sweden)

    Jean Woo

    2010-02-01

    Full Text Available Obesity is a public health problem that has become epidemic worldwide. Substantial literature has emerged to show that overweight and obesity are major causes of co-morbidities, including type II diabetes, cardiovascular diseases, various cancers and other health problems, which can lead to further morbidity and mortality. The related health care costs are also substantial. Therefore, a public health approach to develop population-based strategies for the prevention of excess weight gain is of great importance. However, public health intervention programs have had limited success in tackling the rising prevalence of obesity. This paper reviews the definition of overweight and obesity and the variations with age and ethnicity; health consequences and factors contributing to the development of obesity; and critically reviews the effectiveness of current public health strategies for risk factor reduction and obesity prevention.

  20. Current Approach in Surface Plasmons for Thin Film and Wire Array Solar Cell Applications.

    Science.gov (United States)

    Zhou, Keya; Guo, Zhongyi; Liu, Shutian; Lee, Jung-Ho

    2015-07-22

    Surface plasmons, which exist along the interface of a metal and a dielectric, have been proposed as an efficient alternative method for light trapping in solar cells during the past ten years. With unique properties such as superior light scattering, optical trapping, guide mode coupling, near field concentration, and hot-electron generation, metallic nanoparticles or nanostructures can be tailored to a certain geometric design to enhance solar cell conversion efficiency and to reduce the material costs. In this article, we review current approaches on different kinds of solar cells, such as crystalline silicon (c-Si) and amorphous silicon (a-Si) thin film solar cells, organic solar cells, nanowire array solar cells, and single nanowire solar cells.

  1. Current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis in Europe: the AIR survey

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2014-06-01

    Full Text Available This review presents the results of the 2013 Advancing IPF Research (AIR survey, which assessed current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF by experienced physicians. A total of 149 physicians, predominantly from European countries, replied to the 28-question survey. The results of the AIR survey were compared with a similar survey of 509 French pulmonologists conducted by the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. A number of positive findings emerged from the AIR survey, including the high level of multidisciplinary team involvement in both diagnosis and management. This survey, when taken together with the French survey, suggests that there is still a need to improve earlier diagnosis of IPF.

  2. 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.

  3. 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.

  4. Anti-aging pharmacology: Promises and pitfalls.

    Science.gov (United States)

    Vaiserman, Alexander M; Lushchak, Oleh V; Koliada, Alexander K

    2016-11-01

    Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology.

  5. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Locatelli, Franco; Lucarelli, Barbarella; Merli, Pietro

    2014-01-01

    One significant obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT) is represented by graft failure, defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Graft failure mediated by host immune cells attacking donor stem cells is named graft rejection. Factors associated with graft failure include HLA disparity in the donor/recipient pair, underlying disease, viral infections, type of conditioning regimen and stem cell source employed. In this article, the experts summarize current approaches to treat graft failure/rejection after HSCT, and they discuss new strategies of graft manipulation and immune therapy of particular interest for preventing/treating this complication. A limited array of options is available to treat graft failure. The experts believe that re-transplantation from another donor or the same donor (if there is no evidence of immunologically mediated graft failure) is the treatment of choice for patients with primary graft failure or acute graft rejection. The experts think that strategies based on innovative approaches of graft manipulation, new agents or cellular therapies could render in the future graft failure a much less relevant problem for HSCT recipients.

  6. Modeling left and right atrial contributions to the ECG: A dipole-current source approach.

    Science.gov (United States)

    Jacquemet, Vincent

    2015-10-01

    This paper presents the mathematical formulation, the numerical validation and several illustrations of a forward-modeling approach based on dipole-current sources to compute the contribution of a part of the heart to the electrocardiogram (ECG). Clinically relevant applications include identifying in the ECG the contributions from the right and the left atrium. In a Courtemanche-based monodomain computer model of the atria and torso, 1000 dipoles distributed throughout the atrial mid-myocardium are found to be sufficient to reproduce body surface potential maps with a relative error approach enables fast offline computation of the ECG contribution of any anatomical part of the atria by applying the principle of superposition to the dipole sources. In the presence of a right-left activation delay (sinus rhythm), pulmonary vein isolation (sinus rhythm) or left-right differences in refractory period (atrial fibrillation), the decomposition of the ECG is shown to help interpret ECG morphology in relation to the atrial substrate. These tools provide a theoretical basis for a deeper understanding of the genesis of the P wave or fibrillatory waves in normal and pathological cases.

  7. 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.

  8. 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.

  9. Music therapy as a non-pharmacological treatment for epilepsy.

    Science.gov (United States)

    Liao, Huan; Jiang, Guohui; Wang, Xuefeng

    2015-01-01

    Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies.

  10. Controllable synthesis of metal particles by a direct current electrochemical approach

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Shapes of copper and silver particles were successfully controlled by using a very simple,effective direct-current electrochemical approach without introducing any additives or templates. A diverse range of shapes and also different inner structures were thus accessible. The products prepared at relatively high potentials have flowerlike morphologies and exhibit flakes as building blocks. The uniformly thick flakes intersect mutually,have smooth surfaces and outwardly wavy edges. The particle diameter and the flake density can be easily controlled by changing potential and/or deposition time. With a decrease of potential,the particles’ shapes changed from flower to bud,to sphere and to octahedron. Surface plasmon resonance (SPR) properties of the supported metal particles were investigated by UV-Vis diffuse reflectance spectra (UV-Vis DRS) and surface enhanced Raman scattering (SERS). It was found that the copper octahedra exhibited three characteristic bands,and SERS effect increases with the number of flakes within individual particles. Based on the experimental results,the mechanism for direct-current electrochemical growth of metal nanostructures was discussed.

  11. 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.

  12. 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.

  13. 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

  14. Ocean Current Energy Conversion System in Wallacea Region Using Variable Speed Control Approach

    Directory of Open Access Journals (Sweden)

    Aditya Sukma Nugraha

    2012-03-01

    Full Text Available Ocean Current Energy Conversion System (OCECS is a promising green energy resource in this globe. The Thermohaline circulation data indicates that the Wallacea region has the potential of ocean current energy resources. This paper is aimed to propose research and development of OCECSs to be implemented in the Wallacea region. Firstly, four types of green energy conversion systems extracted from ocean are reviewed. Their advantages and disadvantages are discussed. Secondly, the potential of OCECS in the Wallacea region is described. Third, many types of turbines used for OCECS are reviewed and the turbine type for OCECS is selected to be implemented in the Wallacea region. Fourth, control strategy is proposed.From the work reported in this paper it is concluded that it is appropriate to implement OCECSs using axial flow water turbines in the Wallacea region, and that to maximize energy conversion variable speed control approach is selected together with control of mechanism to move the turbine vertically as well as to rotate the turbine in yaw direction. 

  15. Marketing of library and information services in global era: A current approach

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Karn

    2008-06-01

    Full Text Available This paper deals with the marketing of library and information services in the global era. It discusses about the marketing concept of today's library and information centers covering various topics such as management of libraries and commitment to customer's satisfaction. It also defines the marketing and its current approach to library and information services at the global level. It also describes customer/user's topic such as customers' priorities, customers' expectations, individuality responsiveness, relationships, quality of services, professional skills and competencies and value added services. The 5 Ps of marketing mix, i.e. product, pricing, place, promotion and person (staff have been discussed. The marketing should aim at effective library and information services. The "service trinity", i.e. users (customers, the staff (service provider and information resources and system should be taken care of from the view of these services. In the modern age, the library and information services (LIS are customer (user oriented. Therefore, users' priorities, expectations and needs should be taken into account. The services should be value added according to the current requirement of the users. It is concluded that the modern libraries are information markets and the library users are consumers of information. The ultimate objective of the marketing of library and information services should be the dissemination of the right information to the right customer (user at the right time.

  16. 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.

  17. Current approaches to the management of new-onset ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Marchioni Beery R

    2014-05-01

    Full Text Available Renée Marchioni Beery,1 Sunanda Kane21Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Ulcerative colitis (UC is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to-moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids or thiopurines (as bridging therapy. Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide

  18. 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.

    Science.gov (United States)

    Xu, Haiyu; Zhang, Yanqiong; Lei, Yun; Gao, Xiumei; Zhai, Huaqiang; Lin, Na; Tang, Shihuan; Liang, Rixin; Ma, Yan; Li, Defeng; Zhang, Yi; Zhu, Guangrong; Yang, Hongjun; Huang, Luqi

    2014-01-01

    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.

  19. 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.

  20. 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...

  1. Approaches to Grammar Instruction in Teaching Materials: A Study in Current L2 Beginning-Level Spanish Textbooks

    Science.gov (United States)

    Fernandez, Claudia

    2011-01-01

    This study explores how grammar instruction is conceptualized and applied in published Spanish materials. It sought to answer the following questions: What are the approaches to grammar instruction in current, college-level, beginning Spanish textbooks? How do they reflect current perspectives on grammar teaching? Six widely adopted Spanish…

  2. Approaches to Grammar Instruction in Teaching Materials: A Study in Current L2 Beginning-Level Spanish Textbooks

    Science.gov (United States)

    Fernandez, Claudia

    2011-01-01

    This study explores how grammar instruction is conceptualized and applied in published Spanish materials. It sought to answer the following questions: What are the approaches to grammar instruction in current, college-level, beginning Spanish textbooks? How do they reflect current perspectives on grammar teaching? Six widely adopted Spanish…

  3. Combined transcranial alternating current stimulation and continuous theta burst stimulation: a novel approach for neuroplasticity induction.

    Science.gov (United States)

    Goldsworthy, Mitchell R; Vallence, Ann-Maree; Yang, Ruiting; Pitcher, Julia B; Ridding, Michael C

    2016-02-01

    Non-invasive brain stimulation can induce functionally relevant plasticity in the human cortex, making it potentially useful as a therapeutic tool. However, the induced changes are highly variable between individuals, potentially limiting research and clinical utility. One factor that might contribute to this variability is the level of cortical inhibition at the time of stimulation. The alpha rhythm (~ 8-13 Hz) recorded with electroencephalography (EEG) is thought to reflect pulsatile cortical inhibition; therefore, targeting non-invasive brain stimulation to particular phases of the alpha rhythm may provide an approach to enhance plasticity induction. Transcranial alternating current stimulation (tACS) has been shown to entrain cortical oscillations in a frequency-specific manner. We investigated whether the neuroplastic response to continuous theta burst stimulation (cTBS) was enhanced by timing bursts of stimuli to the peak or the trough of a tACS-imposed alpha rhythm. While motor evoked potentials (MEPs) were unaffected when cTBS was applied in-phase with the peak of the tACS-imposed oscillation, MEP depression was enhanced when cTBS was applied in-phase with the trough. This enhanced MEP depression was dependent on the individual peak frequency of the endogenous alpha rhythm recorded with EEG prior to stimulation, and was strongest in those participants classified as non-responders to standard cTBS. These findings suggest that tACS may be used in combination with cTBS to enhance the plasticity response. Furthermore, the peak frequency of endogenous alpha, as measured with EEG, may be used as a simple marker to pre-select those individuals likely to benefit from this approach.

  4. 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

  5. Xanthomicrol: a comprehensive review of its chemistry, distribution, biosynthesis and pharmacological activity.

    Science.gov (United States)

    Fattahi, Mohammad; Cusido, Rosa M; Khojasteh, Abbas; Bonfill, Mercedes; Palazon, Javier

    2014-01-01

    Highly methoxylated flavones, which have known potential as cancer chemopreventive agents, accumulate on the leaf surfaces of some plant species and their physiological role is to protect the plant against harmful UV radiation. Xanthomicrol is one of the methoxylated flavones currently attracting most attention from researchers worldwide because of its promising pharmacological activities, including anti-spasmodic, anti-platelet and anti-cancer effects, among others. This review covers the chemistry and biological origin, distribution and pharmacological activity of xanthomicrol. Knowledge of the botanical distribution of this compound will not only encourage the use of plant sources for pharmacological purposes, but will also serve as a reference in the search for this valuable flavonoid in another genus or family. New approaches to xanthomicrol production are also described, including biotechnological attempts to develop xanthomicrol-producing plant cell factories.

  6. Pharmacological and clinical properties of curcumin

    Directory of Open Access Journals (Sweden)

    Huang S

    2011-06-01

    Full Text Available Christopher S Beevers¹, Shile Huang²¹Department of Pharmacology, Ross University School of Medicine, Picard-Portsmouth, Commonwealth of Dominica; ²Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: The polyphenol natural product curcumin has been the subject of numerous studies over the past decades, which have identified and characterized the compound's pharmacokinetic, pharmacodynamic, and clinical pharmacological properties. In in vitro and in vivo model systems, curcumin displays potent pharmacological effects, by targeting many critical cellular factors, through a diverse array of mechanisms of action. Despite this tremendous molecular versatility, however, the clinical application of curcumin remains limited due to poor pharmacokinetic characteristics in human beings. The current trend is to develop and utilize unique delivery systems, chemical derivatives, and chemical analogs to circumvent these pharmacological obstacles, in order to optimize the conditions for curcumin as a chemopreventive and chemotherapeutic agent in diseases such as cancer, diabetes, obesity, Alzheimer's disease, and inflammatory disorders. The present work seeks to review recent studies in the basic pharmacological principles and potential clinical applications of curcumin.Keywords: curcumin, pharmacological properties, signal transduction, cellular targets, cancer, inflammation

  7. Treatment of Pancreatic Cancer with Pharmacological Ascorbate.

    Science.gov (United States)

    Cieslak, John A; Cullen, Joseph J

    2015-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.

  8. 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.

  9. Application of Caco-2 Cell Line in Herb-Drug Interaction Studies: Current Approaches and Challenges

    Science.gov (United States)

    Awortwe, C.; Fasinu, P.S.; Rosenkranz, B.

    2015-01-01

    The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions. PMID:24735758

  10. [Current methods in genetic analysis : an approach for genetics-based preventive medicine].

    Science.gov (United States)

    Klein, Hans-Georg; Rost, Imma

    2015-02-01

    Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the "post-genomic era". The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches.

  11. Interventions to reduce the risk of violence toward emergency department staff: current approaches

    Directory of Open Access Journals (Sweden)

    Ramacciati N

    2016-04-01

    Full Text Available Nicola Ramacciati,1,2 Andrea Ceccagnoli,2 Beniamino Addey,3 Enrico Lumini,4 Laura Rasero1,5 1Department of Experimental and Clinical Medicine, University of Florence, 2Emergency Department, S. Maria della Misericordia Hospital, 3Emergency Medical System, S. Maria della Misericordia Hospital, Perugia, 4Department of Health Sciences, University of Florence, 5Research and Development Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy Introduction: The phenomenon of workplace violence in health care settings, and especially in the emergency department (ED, has assumed the dimensions of a real epidemic. Many studies highlight the need for methods to ensure the safety of staff and propose interventions to address the problem. Aim: The aim of this review was to propose a narrative of the current approaches to reduce workplace violence in the ED, with a particular focus on evaluating the effectiveness of emergency response programs. Methods: A search was conducted between December 1, 2015 and December 7, 2015, in PubMed and CINAHL. Ten intervention studies were selected and analyzed. Results: Seven of these interventions were based on sectoral interventions and three on comprehensive actions. Conclusion: The studies that have attempted to evaluate the effectiveness of interventions have shown weak evidence to date. Further research is needed to identify effective actions to promote a safe work environment in the ED. Keywords: workplace violence, violence prevention and control, emergency department, aggression, security, review

  12. Old concepts, new molecules and current approaches applied to the bacterial nucleotide signalling field

    Science.gov (United States)

    2016-01-01

    Signalling nucleotides are key molecules that help bacteria to rapidly coordinate cellular pathways and adapt to changes in their environment. During the past 10 years, the nucleotide signalling field has seen much excitement, as several new signalling nucleotides have been discovered in both eukaryotic and bacterial cells. The fields have since advanced quickly, aided by the development of important tools such as the synthesis of modified nucleotides, which, combined with sensitive mass spectrometry methods, allowed for the rapid identification of specific receptor proteins along with other novel genome-wide screening methods. In this review, we describe the principle concepts of nucleotide signalling networks and summarize the recent work that led to the discovery of the novel signalling nucleotides. We also highlight current approaches applied to the research in the field as well as resources and methodological advances aiding in a rapid identification of nucleotide-specific receptor proteins. This article is part of the themed issue ‘The new bacteriology’. PMID:27672152

  13. Reward Learning as a Potential Target for Pharmacological Augmentation of Cognitive Remediation for Schizophrenia: A Roadmap for Preclinical Development

    Directory of Open Access Journals (Sweden)

    Dean T Acheson

    2013-06-01

    Full Text Available Rationale: Impaired cognitive abilities are a key characteristic of schizophrenia. Although currently approved pharmacological treatments have demonstrated efficacy for positive symptoms, to date no pharmacological treatments successfully reverse cognitive dysfunction in these patients. Cognitively-based interventions such as cognitive remediation (CR and other psychosocial interventions however, may improve some of the cognitive and functional deficits of schizophrenia. Given that these treatments are time-consuming and labor-intensive, maximizing their effectiveness is a priority. Augmenting psychosocial interventions with pharmacological treatments may be a viable strategy for reducing the impact of cognitive deficits in patients with schizophrenia. Objective: We propose a strategy to develop pharmacological treatments that can enhance the reward-related learning processes underlying successful skill-learning in psychosocial interventions. Specifically, we review clinical and preclinical evidence and paradigms that can be utilized to develop these pharmacological augmentation strategies. Prototypes for this approach include dopamine D1 receptor and α7 nicotinic acetylcholine receptor agonists as attractive targets to specifically enhance reward-related learning during CR. Conclusion: The approach outlined here could be used broadly to develop pharmacological augmentation strategies across a number of cognitive domains underlying successful psychosocial treatment.

  14. A new approach to study the effect of generation rate on drain-source current of bilayer graphene transistors

    Science.gov (United States)

    Ahmad, H.; Ghadiry, M.; AbdManaf, A.

    2016-10-01

    This paper presents a new approach to study the effect of impact ionization on the current of bilayer graphene field effect transistors. Analytical models for surface potential and current together with a Monte Carlo approach which include the edge effect scattering are used to calculate the current and generation rate in bilayer graphene transistors due to ionization. FlexPDE simulation is also employed for verification of surface potential modeling. Using the approach, the profile of generation rate, surface potential and current are plotted with respect to several structural parameters. We have shown that ignoring this effect in the modeling will result in an error of up to 10 % for a typical 30 nm bilayer graphene field effect transistor. As a result, we conclude that any analytical study ignoring the ionization is incomplete for bilayer graphene field effect transistors. The model presented here can be applied in optimization of photo detectors based on graphene.

  15. Neuroimmune pharmacology from a neuroscience perspective.

    Science.gov (United States)

    Northrop, Nicole A; Northrup, Nicole A; Yamamoto, Bryan K

    2011-03-01

    The focus of this commentary is to describe how neuroscience, immunology, and pharmacology intersect and how interdisciplinary research involving these areas has expanded knowledge in the area of neuroscience, in particular. Examples are presented to illustrate that the brain can react to the peripheral immune system and possesses immune function and that resident immune molecules play a role in normal brain physiology. In addition, evidence is presented that the brain immune system plays an important role in mediating neurodegenerative diseases, the aging process, and neurodevelopment and synaptic plasticity. The identification of these mechanisms has been facilitated by pharmacological studies and has opened new possibilities for pharmacotherapeutic approaches to the treatment of brain disorders. The emerging field of neuroimmune pharmacology exemplifies this interdisciplinary approach and has facilitated the study of basic cellular and molecular events and disease states and opens avenues for novel therapies.

  16. Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan.

    Science.gov (United States)

    Lanusse, Carlos; Lifschitz, Adrian; Alvarez, Luis

    2015-08-15

    The correct use of pharmacology-based information is critical to design successful strategies for the future of parasite control in livestock animals. Integrated pharmaco-parasitological research approaches have greatly contributed to optimize drug activity. In an attempt to manage drug resistance in helminths of ruminants, combinations of two or more anthelmintics are being used or promoted, based on the fact that individual worms may have a lower degree of resistance to a multiple component formulation, when each chemical has a different mode of action compared to that observed when a single compound is used. However, as emphasized in the current review, the occurrence of potential pharmacokinetic and/or pharmacodynamic interactions between drug components highlights the need for deeper and integrated research to identify the advantages or disadvantages associated with the use of combined drug preparations. This review article provides integrated pharmacokinetic/pharmacodynamic and clinical pharmacology information pertinent to preserve the traditional and modern active ingredients as practical tools for parasite control. Novel pharmacological data on derquantel and monepantel, as representatives of modern anthelmintics for use in livestock, is summarized here. The article also summarizes the pharmaco-parasitological knowledge considered critical to secure and/or extend the lifespan of the recently available novel molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Pharmacological treatment of the obese diabetic patient.

    Science.gov (United States)

    Scheen, A J; Lefebvre, P J

    1993-01-01

    Obesity is a well-known risk factor for non-insulin-dependent (or Type 2) diabetes mellitus. Consequently, reduction of weight excess comes to the front line in the prevention and management of NIDDM. It is only when diet and physical exercise fail that drug treatment should be considered. Pharmacological treatment of obesity should favour drugs which not only promote weight loss, by reducing caloric intake and/or increasing thermogenesis and energy expenditure, but also, and especially, improve insulin sensitivity. Serotoninergic anorectic compounds (dexfenfluramine, fluoxetine) appear to possess, to some extent, all these properties. Metformin significantly reduces insulin resistance and improves glycaemic control without inducing weight gain, and even favouring some weight loss. This biguanide is now considered as the first line drug for the obese diabetic patient. Alpha-glucosidase inhibitors may help to reduce post-prandial glucose excursions but do not promote weight loss per se. Sulfonylureas can be prescribed to an obese patient when hyperglycaemia persists despite diet and the above-mentioned oral agents, but their use should be associated with reinforcement of dietary advices in order to prevent further weight increase; it is also the case for insulin therapy. Finally, drugs specifically stimulating thermogenesis and energy expenditure, new agents sensitizing tissues to the action of insulin and various compounds interfering with lipid metabolism are currently under extensive investigation with promising preliminary results in the obese diabetic patient. In conclusion, obesity remains a major problem in the management of Type 2 diabetes mellitus and this justifies the search for new, safe and effective, pharmacological approaches.

  18. Current management strategy of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bernardino Rampone; Beniamino Schiavone; Antonio Martino; Carmine Viviano; Giuseppe Confuorto

    2009-01-01

    Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons. Surgery, including liver transplantation, is the most important therapeutic approach for patients with this disease. HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative. This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.

  19. Non-pharmacological intervention for memory decline.

    Science.gov (United States)

    Cotelli, Maria; Manenti, Rosa; Zanetti, Orazio; Miniussi, Carlo

    2012-01-01

    Non-pharmacological intervention of memory difficulties in healthy older adults, as well as those with brain damage and neurodegenerative disorders, has gained much attention in recent years. 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 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 and transcranial direct current stimulation to specific cortical areas]. The present review provides an overview of memory rehabilitation in individuals with mild cognitive impairment and in patients with Alzheimer's disease 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.

  20. 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.

  1. 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...

  2. Pharmacology Isotoma Longiflorum

    OpenAIRE

    Cruz Sánchez, César Guillermo; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    We have studied the pharmacology of Isotoma longiflorum plant campanuláceas the family, native to Peru. Was extracted from this plant a crystalline active ingredient. Se ha estudiado la farmacología de la Isotoma longiflorum planta de la familia de las campanuláceas, nativas del Perú. Se extrajo de esta planta un principio activo cristalino.

  3. 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.

  4. 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.

  5. 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.

  6. The impact of "physiological correction" on functional connectivity analysis of pharmacological resting state fMRI

    NARCIS (Netherlands)

    Khalili-Mahani, N.; Chang, C.; Osch, M.J.; Veer, I.M.; Buchem, van M.A.; Dahan, A.; Beckmann, C.F.

    2013-01-01

    Growing interest in pharmacological resting state fMRI (RSfMRI) necessitates developing standardized and robust analytical approaches that are insensitive to spurious correlated physiological signals. However, in pharmacological experiments physiological variations constitute an important aspect of

  7. The role of pharmacology in pediatric oncology

    Energy Technology Data Exchange (ETDEWEB)

    Poplack, D.G.; Massimo, L.; Cornaglia-Ferraris, P

    1987-01-01

    This book contains 25 chapters. Some of the Titles are: Genetic reasons for pharmacologic treatment failure: gene amplification; New approaches to overcome drug resistance; An overview of adverse late effects of cancer chemotherapy in children; the development of 9-substituted purines as immunomodulators; and High dose cisplatinum: a phase II study.

  8. Publication trends in Naunyn-Schmiedeberg's Archives of Pharmacology: focus on pharmacology in Egypt.

    Science.gov (United States)

    El-Mas, Mahmoud M; El-Gowelli, Hanan M; Michel, Martin C

    2013-11-01

    In a previous analysis of the country of origin of papers published in Naunyn-Schmiedeberg's Archives of Pharmacology, a major shift toward contributions from emerging market countries, was noticed in comparison of 2010 to 2001 publications. Repeating such analysis for 2012 publications in the journal confirmed this trend. An interesting new trend was the emerging presence of papers from a variety of Islamic countries including Egypt. Based on this trend, we shortly review the history and current structure of pharmacology in Egypt. It appears that the presence of Egyptian pharmacology in international journals including pharmacology journals has sharply been increasing over the last two decades. Challenges for a continuation of this encouraging trend are being discussed.

  9. Orofacial Pain: Pharmacologic Paradigms for Therapeutic Intervention.

    Science.gov (United States)

    Halpern, Leslie; Willis, Porchia

    2016-04-01

    Pain is a universal experience with profound effects on the physiology, psychology, and sociology of the population. Orofacial pain (OFP) conditions are especially prevalent and can be severely debilitating to a patient's health-related quality of life. Evidence-based clinical trials suggest that pharmacologic therapy may significantly improve patient outcomes either alone or when used as part of a comprehensive treatment plan for OFP. The aim of this article is to provide therapeutic options from a pharmacologic perspective to treat a broad spectrum of OFP. Clinical-based systemic and topical applied pharmaceutical approaches are presented to treat the most common OFP syndromes. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Soft and hard computing approaches for real-time prediction of currents in a tide-dominated coastal area

    Digital Repository Service at National Institute of Oceanography (India)

    Charhate, S.B.; Deo, M.C.; SanilKumar, V.

    limited dataarchitecture, namely the feedforward type (Fig. 1), another, called the Jordan–Elman type (Fig. 3), was also are available [39]. Similarly, the feedforward type of network was trained using back propagation,used, since the latter architecture... of coastal current components. All the approaches employed performed muchmethods and architectures in the last 15 years has brought the ANN to its current level of usefulness. better than the traditional statistical method of harmonic analysis.Similar success...

  11. High Tc Superconducting Materials for Strong Current Applications: Approach at the First Stage

    Institute of Scientific and Technical Information of China (English)

    JIN Jian-xun

    2007-01-01

    Strong current and large-scale application is the most important prospect of high Tc superconductors (HTS). Practical HTS samples in various forms have been produced with high critical currents operated at economic cryogenic temperatures. Engineering applications of those HTS materials have been studied with various HTS prototype devices. The applicable HTS materials produced in different forms are verified in this paper with regard to their strong current characterizations, and the HTS applications are summarized along with the HTS prototypes made.

  12. Pharmacologic management of overactive bladder

    Directory of Open Access Journals (Sweden)

    Sum Lam

    2007-10-01

    Full Text Available Sum Lam1,2, Olga Hilas1,31St. John’s University, College of Pharmacy and Allied Health Professions, Department of Clinical Pharmacy Practice, Queens, New York, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, New York, USA; 3Department of Pharmacy, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USAAbstract: Overactive bladder (OAB is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.Keywords: overactive bladder, urinary incontinence, pharmacologic management, antimuscarinic agents, anticholinergics

  13. Molecular pharmacology of human NMDA receptors

    DEFF Research Database (Denmark)

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard

    2012-01-01

    current knowledge of the relationship between NMDA receptor structure and function. We summarize studies on the biophysical properties of human NMDA receptors and compare these properties to those of rat orthologs. Finally, we provide a comprehensive pharmacological characterization that allows side......-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors. The evaluation of biophysical properties and pharmacological probes acting at different sites on the receptor suggest...... that the binding sites and conformational changes leading to channel gating in response to agonist binding are highly conserved between human and rat NMDA receptors. In summary, the results of this study suggest that no major detectable differences exist in the pharmacological and functional properties of human...

  14. Pharmacology and drug distribution

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, L.R.; Weatherall, T.J.

    1979-08-01

    An overview of the pharmacology of drugs in the treatment of cancer is presented. The discussion begins with the simplest relationship of drugs and particles to one another then proceeds to demonstrate the interrelationship in a biologic system to produce a chemobiodynamic response. The basic principles of pharmacokinetics are reviewed and their correlation with investigational and standard drug therapies is discussed. Voids in the consideration of interactions between chemotherapy and radiotherapy are discussed.

  15. Overview of safety pharmacology.

    Science.gov (United States)

    Goineau, Sonia; Lemaire, Martine; Froget, Guillaume

    2013-12-02

    Safety pharmacology entails the assessment of the potential risks of novel pharmaceuticals for human use. As detailed in the ICH S7A guidelines, safety pharmacology for drug discovery involves a core battery of studies on three vital systems: central nervous (CNS), cardiovascular (CV), and respiratory. Primary CNS studies are aimed at defining compound effects on general behavior, locomotion, neuromuscular coordination, seizure threshold, and vigilance. The primary CV test battery includes an evaluation of proarrhythmic risk using in vitro tests (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation in a large, anesthetized animal. Basic respiratory function can be examined in conscious animals using whole-body plethysmography. This allows for an assessment of whether the sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO2 . Other safety pharmacology topics detailed in this unit are the timing of such studies, ethical and animal welfare issues, and statistical evaluation.

  16. 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.

  17. Current evidence for osteoarthritis treatments.

    Science.gov (United States)

    Anandacoomarasamy, Ananthila; March, Lyn

    2010-02-01

    Osteoarthritis (OA) is the most common form of arthritis and the leading cause of chronic disability among older people. The burden of the disease is expected to rise with an aging population and the increasing prevalence of obesity. Despite this, there is as yet no cure for OA. However, in recent years, a number of potential therapeutic advances have been made, in part due to improved understanding of the underlying pathophysiology. This review provides the current evidence for symptomatic management of OA including nonpharmacological, pharmacological and surgical approaches. The current state of evidence for disease-modifying therapy in OA is also reviewed.

  18. Caustic-based approach to understanding bunching dynamics and current spike formation in particle bunches

    Science.gov (United States)

    Charles, T. K.; Paganin, D. M.; Dowd, R. T.

    2016-10-01

    Current modulations, current spikes, and current horns, are observed in a range of accelerator physics applications including strong bunch compression in Free Electron Lasers and linear colliders, trains of microbunching for terahertz radiation, microbunching instability and many others. This paper considers the fundamental mechanism that drives intense current modulations in dispersive regions, beyond the common explanation of nonlinear and higher-order effects. Under certain conditions, neighboring electron trajectories merge to form caustics, and often result in characteristic current spikes. Caustic lines and surfaces are regions of maximum electron density, and are witnessed in accelerator physics as folds in phase space of accelerated bunches. We identify the caustic phenomenon resulting in cusplike current profiles and derive an expression which describes the conditions needed for particle-bunch caustic formation in dispersive regions. The caustic expression not only reveals the conditions necessary for caustics to form but also where in longitudinal space the caustics will form. Particle-tracking simulations are used to verify these findings. We discuss the broader implications of this work including how to utilize the caustic expression for manipulation of the longitudinal phase space to achieve a desired current profile shape.

  19. A diagrammatic description of the equations of motion, current and noise within the second-order von Neumann approach

    DEFF Research Database (Denmark)

    Karlstrom, O.; Emary, C.; Zedler, P.

    2013-01-01

    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...

  20. 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

  1. Cluster headache: conventional pharmacological management.

    Science.gov (United States)

    Becker, Werner J

    2013-01-01

    Cluster headache pain is very intense, usually increases in intensity very rapidly from onset, and attacks are often frequent. These clinical features result in significant therapeutic challenges. The most effective pharmacological treatment options for acute cluster attack include subcutaneous sumatriptan, 100% oxygen, and intranasal zolmitriptan. Subcutaneous or intramuscular dihydroergotamine and intranasal sumatriptan are additional options. Transitional therapy is applicable mainly for patients with high-frequency (>2 attacks per day) episodic cluster headache, and options include short courses of high-dose oral corticosteroids, dihydroergotamine, and occipital nerve blocks with local anesthetic and steroids. Prophylactic therapy is important both for episodic and chronic cluster headache, and the main options are verapamil and lithium. Verapamil is drug of first choice but may cause cardiac arrhythmias, and periodic electrocardiograms (EKGs) during dose escalation are important. Many other drugs are also in current use, but there is an insufficient evidence base to recommend them.

  2. Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams.

    Science.gov (United States)

    Wong-Ng, W

    2012-01-01

    This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized.

  3. A new approach for modeling of dark current characteristics of quantum wire infrared photodetectors

    Institute of Scientific and Technical Information of China (English)

    H. Barickaby; A. Zarifkar; M. H. Sheikhi

    2011-01-01

    In order to study the dark current characteristics in a quantum wire infrared photodetector (QRIP), the average number of electrons in quantum wires (QRs) must be got, which is mostly too complicated. In this paper we give a simple formula to calculate the average number of carriers in a quantum wire (QR) that can be easily evaluated by mathematical softwares, and then we use this formula to study dark current characteristics ora quantum wire infrared photodetector (QRIP).

  4. Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach.

    Science.gov (United States)

    Gudala, Suresh; Khan, Uzma; Kanungo, Niteesh; Bandaru, Srinivas; Hussain, Tajamul; Parihar, Ms; Nayarisseri, Anuraj; Mundluru, Hema Prasad

    2015-01-01

    Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound- AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.

  5. Pharmacological Management of Atrial Fibrillation: One, None, One Hundred Thousand

    Directory of Open Access Journals (Sweden)

    Fabiana Lucà

    2011-01-01

    This paper summarizes the available evidence regarding the efficacy of medications used for acute management of AF, rhythm and ventricular rate control, and stroke prevention in patients with atrial fibrillation and focuses on the current pharmacological agents.

  6. Pharmacological Therapy of Gastroesophageal Reflux in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Luigi Corvaglia

    2013-01-01

    Full Text Available Although gastroesophageal reflux (GER is a very common phenomenon among preterm infants, its therapeutic management is still an issue of debate among neonatologists. A step-wise approach should be advisable, firstly promoting nonpharmacological interventions and limiting drugs to selected infants unresponsive to the conservative measures or who are suffering from severe GER with clinical complications. Despite of this, a concerning pharmacological overtreatment has been increasingly reported. Most of the antireflux drugs, however, have not been specifically assessed in preterm infants; moreover, serious adverse effects have been noticed in association to their administration. This review mainly aims to draw the state of the art regarding the pharmacological management of GER in preterm infants, analyzing the best piecies of evidence currently available on the most prescribed anti-reflux drugs. Although further trials are required, sodium alginate-based formulations might be considered promising; however, data regarding their safety are still limited. Few piecies of evidence on the efficacy of histamine-2 receptor blockers and proton pump inhibitors in preterm infants with GER are currently available. Nevertheless, a significantly increased risk of necrotizing enterocolitis and infections has been largely reported in association with their use, thereby leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide in GER’s improvement still needs to be clarified. Other prokinetic agents, such as domperidone and erythromycin, have been reported to be ineffective, whereas cisapride has been withdrawn due to its remarkable cardiac adverse effects.

  7. Metalloprotein and metallo-DNA/RNAzyme design: current approaches, success measures, and future challenges.

    Science.gov (United States)

    Lu, Yi

    2006-12-11

    Specific metal-binding sites have been found in not only proteins but also DNA and RNA molecules. Together these metalloenzymes consist of a major portion of the enzyme family and can catalyze some of the most difficult biological reactions. Designing these metalloenzymes can be both challenging and rewarding because it can provide deeper insights into the structure and function of proteins and cheaper and more stable alternatives for biochemical and biotechnological applications. Toward this goal, both rational and combinatorial approaches have been used. The rational approach is good for designing metalloenzymes that are well characterized, such as heme proteins, while the combinatorial approach is better at designing those whose structures are poorly understood, such as metallo-DNA/RNAzymes. Among the rational approaches, de novo design is at its best when metal-binding sites reside in a scaffold whose structure has been designed de novo (e.g., alpha-helical bundles). Otherwise, design using native scaffolds can be equally effective, allowing more choices of scaffolds whose structural stability is often more resistant to multiple mutations. In addition, computational and empirical designs have both enjoyed successes. Because of the limitation in defining structural parameters for metal-binding sites, a computational approach is restricted to mostly metal-binding sites that are well defined, such as mono- or homonuclear centers. An empirical approach, even though it is less restrictive in the metal-binding sites to be designed, depends heavily on one's knowledge and choice of templates and targets. An emerging approach is a combination of both computational and empirical approaches. The success of these approaches can be measured not only by three-dimensional structural comparison between the designed and target enzymes but also by the total amount of insight obtained from the design process and studies of the designed enzymes. One of the biggest advantages of

  8. Pharmacological interventions for phantom limb pain

    Institute of Scientific and Technical Information of China (English)

    FANG Jun; LIAN Yan-hong; XIE Kang-jie; CAI Shu-nü

    2013-01-01

    Objective To review the mechanisms and current clinical application of pharmacological interventions for phantom limb pain.Data sources Both Chinese and English language literatures were searched using MEDLINE (1982-2011),Pubmed (1982-2011) and the Index of Chinese Language Literature (1982-2011).Study selection Data from published articles about pharmacological management of phantom limb pain in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 96 articles which are listed in the reference section of this review.Results By reviewing the mechanisms and current clinical application of pharmacological interventions for phantom limb pain,including anticonvulsants,antidepressants,local anaesthetics,N-methyl-D-aspartate receptor antagonists,non-steroidal anti-inflammatory drugs,tramadol,opioids,calcitonin,capsaicin,beta-adrenergic blockers,clonidine,muscle relaxants,and emerging drugs,we examined the efficacy and safety of these medications,outlined the limitations and future directions.Conclusions Although there is lack of evidence-based consensus guidelines for the pharmacological management of phantom limb pain,we recommend tricyclic antidepressants,gabapentin,tramadol,opioids,local anaesthetics and N-methyl-D-aspartate receptor antagonists as the rational options for the treatment of phantom limb pain.

  9. Approach for Wide Use of Diagnostic Method for XLPE Cables Using Harmonics in AC Loss Current

    Science.gov (United States)

    Tsujimoto, Tomiyuki; Nakade, Masahiko; Yagi, Yukihiro; Ishii, Noboru

    Water tree is one of the degradation aspects of XLPE cables used for under-ground distribution or transmission lines. We have developed the loss current method using 3rd harmonic in AC loss current for cable diagnosis. Harmonic components in loss current arise as a result of the non-linear voltage-current characteristics of water trees. We confirmed that the 3rd harmonic in AC loss current had good correlation with water tree growth and break down strength. After that, we have applied this method to the actual 66kV XLPE cable lines. Up to now, the number of the application results is more than 130 lines. In case of cable lines terminated at gas-insulated switchgear (GIS), we have to remove the lightning arrestor (LA) and the potential transformer (PT) out of the test circuit. The reason is that we are afraid that each of LA and PT disturbs the degradation signal from cable lines. It takes extra time (1 or 2 days) and costs more to remove LA and PT in GIS out of a circuit. In order to achieve easy and reasonable diagnosis, we have developed a new method for cable lines terminated at GIS, by utilizing a technique, which enables to reduce signal of LA and PT from disturbed signal of cable lines. We confirmed the effect of the new method by experiments with actual cables.

  10. Variational approach to low-frequency kinetic-MHD in the current coupling scheme

    Science.gov (United States)

    Burby, Joshua W.; Tronci, Cesare

    2017-04-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which obeys a kinetic equation. In this work we apply Hamilton’s variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling schemes, in which energetic particle dynamics are expressed in either guiding center or gyrocenter coordinates. When guiding center theory is used to model the hot particles, we show how energy conservation requires corrections to the standard magnetization term. On the other hand, charge and momentum conservation in gyrokinetic-MHD lead to extra terms in the usual definition of the hot current density as well as modifications to conventional gyrocenter dynamics. All these new features arise naturally from the underlying variational structure of the proposed models.

  11. Current conservation in electrodisintegration of a bound system in the Bethe-Salpeter approach

    CERN Document Server

    Karmanov, V A

    2014-01-01

    Using our solutions of the Bethe-Salpeter equation with OBE kernel in Minkowski space both for the bound and scattering states, we calculate the transition form factors for electrodisintegration of the bound system which determine the electromagnetic current J of this process. Special emphasis is put on verifying the gauge invariance which should manifest itself in the current conservation. We find that for any value of the momentum transfer q the contributions of the plane wave and the final state interaction to the quantity J.q cancel each other thus providing J.q=0. However, this cancellation is obtained only if the initial Bethe-Salpeter amplitude (bound state), the final one (scattering state) and the current operator are strictly consistent with each other. A reliable result for the transition form factor can be found only in this case.

  12. New approaches in the design of magnetic tweezers-current magnetic tweezers

    Science.gov (United States)

    Bessalova, Valentina; Perov, Nikolai; Rodionova, Valeria

    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 2·10-11 A m2 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.

  13. Master Equation Approach to Current-Voltage Characteristics of Solar Cells

    Science.gov (United States)

    Oh, Sangchul; Zhang, Yiteng; Alharbi, Fahhad; Kais, Sabre

    2015-03-01

    The current-voltage characteristics of solar cells is obtained using quantum master equations for electrons, holes, and excitons, in which generation, recombination, and transport processes are taken into account. As a first example, we simulate a photocell with a molecular aggregate donor to investigate whether a delocalized quantum state could enhance the efficiency. As a second example, we calculate the current-voltage characteristics of conventional p-n junction solar cells and perovskite solar cells using the master equation. The connection between the drift-diffusion model and the master equation method is established. The short-circuit current and the open-circuit voltage are calculated numerically as a function of the intensity of the sunlight and material properties such as energy gaps, diffusion constants, etc.

  14. 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.

  15. New active-only grounded inductance simulator employing current-mode approach suitable for wide band operation

    Science.gov (United States)

    Yamacli, Serhan; Ozcan, Sadri; Kuntman, Hakan

    2011-08-01

    In this paper, an active-only grounded lossless inductance simulator operating in current-mode is presented. The circuit uses only a current operational amplifier (COA) and an operational transconductance amplifier (OTA). The novelty of the proposed circuit is that it uses a COA instead of a voltage operational amplifier (VOA) to take the wider frequency operation advantage of the current-mode approach. The simulation results obtained through SPICE with 0.5 μm standard CMOS technology verify that the designed circuit can be operated up to 30 MHz, which is much higher than the operation frequency of previously reported inductance simulators utilising VOAs. The inductance value of the presented circuit can be adjusted electronically between 3.9 μH and 37 μH via the biasing current of the OTA. A parallel resonance circuit application is also given validating the operation of the proposed inductance simulator.

  16. Pharmacological treatment of schizophrenia.

    Science.gov (United States)

    Leucht, S; Heres, S; Kissling, W; Davis, J M

    2013-05-01

    We present the pharmacological treatment of schizophrenia based on a simple algorithm that starts with the most important decisions starting from the choice of an antipsychotic drug for an acutely ill patient and ends with maintenance treatment. It represents experts opinions, a formal guideline development process was not followed. Concerning acute treatment we present recommendations for the choice of drug in acutely patients, the treatment of agitated patients, persistent depression, negative symptoms and treatment resistance. Concerning maintenance treatment with antipsychotics we discuss indication, choice of drug, continuous versus intermittent treatment, duration of relapse prevention and dose.

  17. The pharmacology game.

    Science.gov (United States)

    Batscha, Catherine

    2002-09-01

    This article gives instructions for designing a visually attractive, entertaining, faculty-led computer game for pharmacology review in a nursing education program. The game uses Microsoft PowerPoint, a presentation program that is inexpensive, easy to master, and widely available. Instructions for using Visual Basic for Applications to customize the game are included to allow tracking questions asked and the score of groups playing the game. The game can be easily adapted to material by specific nursing programs with access to PowerPoint.

  18. 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.

  19. Analytical pharmacology: the impact of numbers on pharmacology.

    Science.gov (United States)

    Kenakin, Terry; Christopoulos, Arthur

    2011-04-01

    Analytical pharmacology strives to compare pharmacological data to detailed quantitative models. The most famous tool in this regard is the Black/Leff operational model, which can be used to quantify agonism in a test system and predict it in any other system. Here we give examples of how and where analytical pharmacology has been used to classify drugs and predict mechanism of action in pharmacology. We argue for the importance of analytical pharmacology in drug classification and in prediction of drug mechanisms of action. Although some of the specifics of Black's models have been updated to account for new developments, the principles of analytical pharmacology should shape drug discovery for many years to come.

  20. 75 FR 8368 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-02-24

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... certain drugs; (2) a new patient-centric clinical pharmacology approach to drug safety; (3) the design and...

  1. Current Cognitive Distortion Theory and Research: An Internalist Approach to Cognition

    Science.gov (United States)

    Gannon, Theresa A.

    2009-01-01

    This review examines contemporary cognitive distortion theory and research relating to sexual offenders. In particular, this review highlights that researchers--to date--have tended to adopt an internalist approach to sexual offenders' cognition which views offence-supportive cognitive activity as occurring solely within the mind. This review…

  2. 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…

  3. A Phenomenological Approach to Experiences with Technology: Current State, Promise, and Future Directions for Research

    Science.gov (United States)

    Cilesiz, Sebnem

    2011-01-01

    In this paper I conceptualize experiences with technology as an object of study for educational technology research and propose phenomenology as a highly suitable method for studying this construct. I begin by reviewing existing research focusing on the construct of experiences with technology and the approaches utilized for its study. To augment…

  4. Current Cognitive Distortion Theory and Research: An Internalist Approach to Cognition

    Science.gov (United States)

    Gannon, Theresa A.

    2009-01-01

    This review examines contemporary cognitive distortion theory and research relating to sexual offenders. In particular, this review highlights that researchers--to date--have tended to adopt an internalist approach to sexual offenders' cognition which views offence-supportive cognitive activity as occurring solely within the mind. This review…

  5. 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.

  6. Current training on the basics of robotic surgery in the Netherlands: time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, W.; Angst, I. de; Schreuder, H.; Schout, B.M.A.; Draaisma, W.; Verweij, L.; Hendrikx, A.; Poel, H. van der

    2016-01-01

    Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  7. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    W. Brinkman (Willem); I. de Angst (Isabel); H.W.R. Schreuder (Henk); B. Schout (Barbara); W.A. Draaisma (Werner); L.M. Verweij (Lisanne); A.J.M. Hendrikx (A. J M); H.G. van der Poel (Henk G.)

    2017-01-01

    textabstractIntroduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary

  8. Chronic ischaemic mitral regurgitation. Current treatment results and new mechanism-based surgical approaches

    NARCIS (Netherlands)

    Bouma, Wobbe; van der Horst, Iwan C. C.; Wijdh-den Hamer, Inez J.; Erasmus, Michiel E.; Zijlstra, Felix; Mariani, Massimo A.; Ebels, Tjark

    2010-01-01

    Chronic ischaemic mitral regurgitation (CIMR) remains one of the most complex and unresolved aspects in the management of ischaemic heart disease. This review provides an overview of the present knowledge about the different aspects of CIMR with an emphasis on mechanisms, current surgical treatment

  9. 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 emph

  10. Extreme precipitation and temperature responses to circulation patterns in current climate: statistical approaches

    NARCIS (Netherlands)

    Photiadou, C.

    2015-01-01

    Climate change is likely to influence the frequency of extreme extremes - temperature, precipitation and hydrological extremes, which implies increasing risks for flood and drought events in Europe. In current climate, European countries were often not sufficiently prepared to deal with the great so

  11. Current training on the basics of robotic surgery in the Netherlands: time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, W.; Angst, I. de; Schreuder, H.; Schout, B.M.A.; Draaisma, W.; Verweij, L.; Hendrikx, A.; Poel, H. van der

    2016-01-01

    Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  12. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, Willem; de Angst, Isabel; Schreuder, Henk; Schout, Barbara; Draaisma, Werner; Verweij, Lisanne; Hendrikx, Ad; van der Poel, Henk

    Introduction The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  13. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    W. Brinkman (Willem); I. de Angst (Isabel); H.W.R. Schreuder (Henk); B. Schout (Barbara); W.A. Draaisma (Werner); L.M. Verweij (Lisanne); A.J.M. Hendrikx (A. J M); H.G. van der Poel (Henk G.)

    2017-01-01

    textabstractIntroduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary

  14. 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...

  15. 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…

  16. Random-matrix-theory approach to mesoscopic fluctuations of heat current.

    Science.gov (United States)

    Schmidt, Martin; Kottos, Tsampikos; Shapiro, Boris

    2013-08-01

    We consider an ensemble of fully connected networks of N oscillators coupled harmonically with random springs and show, using random-matrix-theory considerations, that both the average phonon heat current and its variance are scale invariant and take universal values in the large N limit. These anomalous mesoscopic fluctuations is the hallmark of strong correlations between normal modes.

  17. 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...

  18. 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 in

  19. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, Willem; de Angst, Isabel; Schreuder, Henk|info:eu-repo/dai/nl/304815977; Schout, Barbara; Draaisma, Werner; Verweij, Lisanne; Hendrikx, Ad; van der Poel, Henk

    2017-01-01

    Introduction The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  20. On wind Turbine failure detection from measurements of phase currents: a permutation entropy approach

    CERN Document Server

    Ram, Sumit Kumar; Molinas, Marta

    2016-01-01

    This article presents the applicability of Permutation Entropy based complexity measure of a time series for detection of fault in wind turbines. A set of electrical data from one faulty and one healthy wind turbine were analysed using traditional FastFourier analysis in addition to Permutation Entropy analysis to compare the complexity index of phase currents of the two turbines over time. The 4 seconds length data set did not reveal any low frequency in the spectra of currents, neither did they show any meaningful differences of spectrum between the two turbine currents. Permutation Entropy analysis of the current waveforms of same phases for the two turbines are found to have different complexity values over time, one of them being clearly higher than the other. The work of Yan et. al. in has found that higher entropy values related to thepresence of failure in rotary machines in his study. Following this track, further efforts will be put into relating the entropy difference found in our study to possible...

  1. 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…

  2. The effectiveness of current approaches to workplace stress management in the nursing profession: an evidence based literature review

    Science.gov (United States)

    Mimura, C; Griffiths, P

    2003-01-01

    The effectiveness of current approaches to workplace stress management for nurses was assessed through a systematic review. Seven randomised controlled trials and three prospective cohort studies assessing the effectiveness of a stress management programmes were identified and reviewed. The quality of research identified was weak. There is more evidence for the effectiveness of programmes based on providing personal support than environmental management to reduce stressors. However, since the number and quality of studies is low, the question as to which, if any, approach is more effective cannot be answered definitively. Further research is required before clear recommendations for the use of particular interventions for nursing work related stress can be made. PMID:12499451

  3. CHOICE OF SURGICAL APPROACH FOR ACETABULAR COMPONENT’S IMPLANTATION USING CURRENT CLASSIFICATION FOR ARTHRITIS FOLLOWING ACETABULAR FRACTURE

    Directory of Open Access Journals (Sweden)

    R. M. Tikhilov

    2011-01-01

    Full Text Available Degenerative-dystrophic changes in hip after treatment of acetabular fracture, over the time, develops about in 60% of affected people. In such cases, total hip replacement is used. Existing classifications (for example AO or Letournel are good for fracture treatment, but not for arthritis following acetabular fracture. The group of patients, with post traumatic arthritis, is heterogeneous with severity of post traumatic anatomic changes. Basis for surgical approach, could be current classification for post traumatic changes – taking into account features of anatomic functional changes in hip and the bone defects of acetabulum. In this article is demonstrated X-ray and clinical basing for current classification.

  4. Epigenetics and pharmacology

    Science.gov (United States)

    Stefanska, Barbara; MacEwan, David J

    2015-01-01

    Recent advances in the understanding of gene regulation have shown there to be much more regulation of the genome than first thought, through epigenetic mechanisms. These epigenetic mechanisms are systems that have evolved to either switch off gene activity altogether, or fine-tune any existing genetic activation. Such systems are present in all genes and include chromatin modifications and remodelling, DNA methylation (such as CpG island methylation rates) and histone covalent modifications (e.g. acetylation, methylation), RNA interference by short interfering RNAs (siRNAs) and long non-coding RNAs (ncRNAs). These systems regulate genomic activity ‘beyond’ simple transcriptional factor inducer or repressor function of genes to generate mRNA. Epigenetic regulation of gene activity has been shown to be important in maintaining normal phenotypic activity of cells, as well as having a role in development and diseases such as cancer and neurodegenerative disorders such as Alzheimer's. Newer classes of drugs regulate epigenetic mechanisms to counteract disease states in humans. The reports in this issue describe some advances in epigenetic understanding that relate to human disease, and our ability to control these mechanisms by pharmacological means. Increasingly the importance of epigenetics is being uncovered – it is pharmacology that will have to keep pace. PMID:25966315

  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. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

    Science.gov (United States)

    Maione, Paolo; Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-09-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC.

  7. Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

    Science.gov (United States)

    Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

    2016-09-01

    Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

  8. Transition electromagnetic form factor and current conservation in the Bethe-Salpeter approach

    CERN Document Server

    Carbonell, J

    2015-01-01

    The transition form factor for electrodisintegration of a two-body bound system is calculated in the Bethe-Salpeter framework. For the initial (bound) and the final (scattering) states, we use our solutions of the Bethe-Salpeter equation in Minkowski space which were first obtained recently. The gauge invariance, which manifests itself in the conservation of the transition electromagnetic current Jq = 0, is studied numerically. It results from a cancellation between the plane wave and the final state interaction contributions. This cancellation takes place only if the initial bound state BS amplitude, the final scattering state and the operator of electromagnetic current are strictly consistent with each other, that is if they are found in the same dynamical framework. A reliable result for the transition form factor can be obtained in this case only.

  9. An evaluation of pharmacology curricula in Australian science and health-related degree programs.

    Science.gov (United States)

    Lloyd, Hilary; Hinton, Tina; Bullock, Shane; Babey, Anna-Marie; Davis, Elizabeth; Fernandes, Lynette; Hart, Joanne; Musgrave, Ian; Ziogas, James

    2013-11-19

    Pharmacology is a biomedical discipline taught in basic science and professional degree programs. In order to provide information that would facilitate pharmacology curricula to be refined and developed, and approaches to teaching to be updated, a national survey was undertaken in Australia that investigated pharmacology course content, teaching and summative assessment methods. Twenty-two institutions participated in a purpose-built online questionnaire, which enabled an evaluation of 147 courses taught in 10 different degrees. To enable comparison, degrees were grouped into four major degree programs, namely science, pharmacy, medicine and nursing. The pharmacology content was then classified into 16 lecture themes, with 2-21 lecture topics identified per theme. The resultant data were analysed for similarities and differences in pharmacology curricula across the degree programs. While all lecture themes were taught across degree programs, curriculum content differed with respect to the breadth and hours of coverage. Overall, lecture themes were taught most broadly in medicine and with greatest coverage in pharmacy. Reflecting a more traditional approach, lectures were a dominant teaching method (at least 90% of courses). Sixty-three percent of science courses provided practical classes but such sessions occurred much less frequently in other degree programs, while tutorials were much more common in pharmacy degree programs (70%). Notably, problem-based learning was common across medical programs. Considerable diversity was found in the types of summative assessment tasks employed. In science courses the most common form of in-semester assessment was practical reports, whereas in other programs pen-and-paper quizzes predominated. End-of-semester assessment contributed 50-80% to overall assessment across degree programs. The similarity in lecture themes taught across the four different degree programs shows that common knowledge- and competency-based learning

  10. Peripheral T-cell lymphomas: A review of current approaches and hopes for the future.

    Directory of Open Access Journals (Sweden)

    Alan Pierre Skarbnik

    2013-05-01

    Full Text Available Peripheral T-cell lymphomas comprise a heterogeneous group of NHLs, with different clinical and biological behaviors, but with a common denominator of poor overall prognosis and lack of potentially curable approaches outside of the realm of stem cell transplantation. Recent data have elicited renewed hope in the treatment of this disease. The authors review the standard of care in treating PTCL, as well as novel therapeutic modalities.

  11. 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.

  12. 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.

  13. The generalized BLM approach to fix scale-dependence in QCD: the current status of investigations

    CERN Document Server

    Kataev, A L

    2014-01-01

    I present a brief review of the generalized Brodsky-Lepage-McKenzie (BLM) approaches to fix the scale-dependence of the renormalization group (RG) invariant quantities in QCD. At first, these approaches are based on the expansions of the coefficients of the perturbative series for the RG-invariant quantities in the products of the coefficients $\\beta_i$ of the QCD $\\beta$-function, which are evaluated in the MS-like schemes. As a next step all $\\beta_i$-dependent terms are absorbed into the BLM-type scale(s) of the powers of the QCD couplings. The difference between two existing formulations of the above mentioned generalizations based on the seBLM approach and the Principle of Maximal Conformality (PMC) are clarified in the case of the Bjorken polarized deep-inelastic scattering sum rule. Using the conformal symmetry-based relations for the non-singlet coefficient functions of the Adler D-function and of Bjorken polarized deep-inelastic scattering sum rules $C^{\\rm Bjp}_{\\rm NS}(a_s)$ the $\\beta_i$-dependent...

  14. 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.

  15. Society for Maternal-Fetal Medicine (SMFM) Special Report: Current approaches to measuring quality of care in obstetrics.

    Science.gov (United States)

    Bailit, Jennifer L; Gregory, Kimberly D; Srinivas, Sindhu; Westover, Thomas; Grobman, William A; Saade, George R

    2016-09-01

    Heath care measurement and evaluation is an integral piece of the health care system. The creation and assessment of care performance metrics are important and relevant for the obstetric community including both clinicians and patients. Careful deliberation is required to create a measurement system that results in optimal care for women and families. This article reviews the current approaches to measuring quality in obstetrics. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A Combined EOF/Variational Approach for Mapping Radar-Derived Sea Surface Currents

    Science.gov (United States)

    2011-01-01

    assess the method’s skill and compare it with the conventional 2d variational (2dVar) approach. It is shown that the proposed technique consistently...radial velocities are interpolated on the regular grid. Experiments with simulated and real data are used to assess the method’s skill and compare it...velocities v(x,) observed outside the gap (x, efl \\<u) are expanded in Kr "resolved" eigenfunctions e* of C: find otk: £ v(Xj)- ]T 0Lke"(x,) X, . I/lU

  17. Current Trends in Psychological and Educational Approaches for Training and Teaching Students with Autism in California

    Directory of Open Access Journals (Sweden)

    Trisha SUGITA

    2016-12-01

    Full Text Available Within the United States, Autism Spectrum Disorder (ASD has seen a dramatic increase over the past twenty years. As the prevalence rate of ASD increases, an increased need for expertise in the field of education has become apparent. Psychological and educational practices for training and teaching students with ASD continue to evolve in California however, a significant gap between theory and practice remains. This article provides a historical perspective of ASD and its prevalence rates. In addition, this article examines the current shifts in teacher training and provides an overview of evidence-based strategies to support students with ASD.

  18. Choosing Wisely: assessment of current US top five list recommendations’ trustworthiness using a pragmatic approach

    Science.gov (United States)

    Horvath, Karl; Semlitsch, Thomas; Jeitler, Klaus; Abuzahra, Muna E; Posch, Nicole; Domke, Andreas; Siebenhofer, Andrea

    2016-01-01

    Objectives Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. Setting Not applicable. Participants All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. Main outcome measures/interventions Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an ‘A’ GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. Results 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an ‘A’ GoR, or a strong recommendation based on strong evidence, and 26 had a ‘B’ or a ‘C’ GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. Conclusions 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number

  19. Choosing Wisely: assessment of current US top five list recommendations' trustworthiness using a pragmatic approach.

    Science.gov (United States)

    Horvath, Karl; Semlitsch, Thomas; Jeitler, Klaus; Abuzahra, Muna E; Posch, Nicole; Domke, Andreas; Siebenhofer, Andrea

    2016-10-07

    Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. Not applicable. All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an 'A' GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an 'A' GoR, or a strong recommendation based on strong evidence, and 26 had a 'B' or a 'C' GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological

  20. Current Research and Classroom Practice: Toward More Inclusive Approaches to Literacy Development in Schools

    Directory of Open Access Journals (Sweden)

    David Booth

    2009-07-01

    Full Text Available This paper offers an exploration of current research and related practice in boys’ literacy development, interprets key findings in the literature, and further explores some of the complex dilemmas and debates related to the ‘gender gap’ – i.e., differences between the achievement of boys and girls in this area. In conclusion, the authors suggest that governments, policy-makers, administrators, teachers and parents all need to closely examine and consider available research-based strategies and classroom interventions that can effectively support both boys and girls in their literacy development.