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  1. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

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

  2. Clinical pharmacology of homoharringtonine

    International Nuclear Information System (INIS)

    Savaraj, N.; Lu, K.; Dimery, I.; Feun, L.G.; Burgess, M.; Keating, M.; Loo, T.L.

    1986-01-01

    Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total [ 3 H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total [ 3 H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3 H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine

  3. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

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

    Science.gov (United States)

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

    2016-01-01

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

  5. The Dutch vision of clinical pharmacology

    NARCIS (Netherlands)

    Schellens, J H M; Grouls, R; Guchelaar, H J; Touw, D J; Rongen, G A; de Boer, A; Van Bortel, L M

    Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether

  6. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  7. Methods in Clinical Pharmacology Series

    Science.gov (United States)

    Beaumont, Claire; Young, Graeme C; Cavalier, Tom; Young, Malcolm A

    2014-01-01

    Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules. PMID:25041729

  8. Electronic cigarettes and nicotine clinical pharmacology

    OpenAIRE

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abst...

  9. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

    To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

  10. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  11. Only connect: the merger of BMC Pharmacology and BMC Clinical Pharmacology.

    Science.gov (United States)

    Moylan, Elizabeth C; Morrey, Christopher; Appleford-Cook, Joanne M

    2012-08-13

    This editorial celebrates the launch of BMC Pharmacology and Toxicology within the BMC series of journals published by BioMed Central. The scope of the journal is interdisciplinary encompassing toxicology, experimental and clinical pharmacology including clinical trials. In this editorial we discuss the origins of this new journal and the ethos and policies under which it will operate.

  12. Radioimmunoassay in basic and clinical pharmacology

    International Nuclear Information System (INIS)

    Patrono, C.; Peskar, B.A.

    1987-01-01

    The subject of the book is the development, validation and application of radioimmunoassay (RIA) techniques for the measurement of a variety of substances in animal and human body fluids. The book discusses methodological and conceptual issues related to the main classes of mediators of drug action and to drugs themselves, as assayed by this particular analytical technique. A number of introductory chapters provide basic information concerning production and characterization of antibodies, labeling techniques, statistical aspects and validation criteria, insight into problems related to the development and validation of RIA for the newly discovered mediator(s). In the following chapters, the emphasis is placed on the technical details relevant to each class of compounds and on specific aspects of their applications to basic and/or clinical pharmacological studies. New developments in this area, such as monoclonal antibodies and non-radioactive labeling techniques, are also covered

  13. Clinical pharmacology of atovaquone and proguanil hydrochloride.

    Science.gov (United States)

    Beerahee, M

    1999-05-01

    Atovaquone and proguanil hydrochloride is a new antimalarial combination that is used for treatment and prophylaxis of malaria. The clinical pharmacology of atovaquone and proguanil was reviewed. Atovaquone is a highly lipophilic compound with low aqueous solubility, the absorption of which is limited by the rate and extent of dissolution. Dietary fat increases the rate and extent of atovaquone absorption, increasing AUC two- to threefold and C(max) fivefold over fasting. Proguanil is rapidly and extensively absorbed regardless of food intake. Atovaquone is highly protein bound (> 99%) but does not displace other highly protein bound drugs in vitro, indicating significant drug interactions arising from displacement are unlikely. Atovaquone is predominantly eliminated unchanged in feces, with negligible excretion in urine. Proguanil is partially metabolized and partially excreted unchanged in urine. Its principal metabolite, cycloguanil, is also excreted in urine. Metabolism of proguanil is mediated in the liver by the cytochrome P450 3A and 2C subfamilies. The elimination half-life of atovaquone is 2 to 3 days in adults and 1 to 2 days in children. The elimination half-lives of proguanil and cycloguanil are 12 to 15 hours in adults and children. Dosage adjustments based on body weight categories in children (1/4 dose for 11-20 kg, 1/2 dose for > 20-30 kg, 3/4 dose for > 30-40 kg, and full dose for > 40 kg) achieve plasma concentrations that are safe and effective during prophylaxis and treatment of malaria. No dose adjustments for race, proguanil metabolizer status, gender, or elderly patients are needed, or for patients with mild to moderately impaired renal or hepatic function. The clinical pharmacology of atovaquone and proguanil provides a rationale for the dosing regimens recommended for treatment and prophylaxis of malaria.

  14. 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.

  15. Pharmacological Activity and Clinical Use of PDRN

    Directory of Open Access Journals (Sweden)

    Francesco Squadrito

    2017-04-01

    Full Text Available PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout or Oncorhynchus keta (Chum Salmon sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

  16. Pharmacological Activity and Clinical Use of PDRN

    Science.gov (United States)

    Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

    2017-01-01

    PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

  17. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  18. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    Directory of Open Access Journals (Sweden)

    Chanin Clark Wright

    2013-12-01

    Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

  19. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... The US database, on the other hand, clearly identifies 172 ... operating within extended clinical trials R&D value chains. Companies often ... Source: CeSTII Survey Management and Results System internal database. Table III.

  20. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  1. The internet as a tool in clinical pharmacology

    Science.gov (United States)

    Castel, Josep-Maria; Figueras, Albert; Vigo, Joan-Miquel

    2006-01-01

    The invention of the internet and the world-wide web was a landmark that has affected many aspects of everyday life, but is so recent and dynamic that many of its potential uses are still being explored. Aside from its purely commercial use as a virtual pharmacy (e-commerce), the internet is useful in at least three aspects related to clinical pharmacology: communication, training and research. In this paper we briefly review several internet applications related to clinical pharmacology and describe, as an example, the logistics of a multicentre research collaboration related to the promotion of rational drug use in the prevention of postpartum haemorrhage. PMID:16722847

  2. A Clinical Pharmacology Course for Veterinary Students.

    Science.gov (United States)

    Paulsen, Lynn Mulcahy

    1983-01-01

    A one-semester, two-credit course is described that was developed cooperatively by the colleges of pharmacy and veterinary medicine at Washington State University to help resolve an acute shortage of clinical pharmacologists in veterinary medicine and veterinary medical education. Course procedures, content, and evaluation are outlined (MSE)

  3. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... companies to manufacture pharmaceuticals, 24 to carry out quality control and ... represents a 3% real growth from 2004/2005, it represents a slight decline from ... manufacturer for the pharmas, or can it leverage strengths in medical ... increased clinical trials activity, R&D investment is too low to make it a ...

  4. Clinical Pharmacology Studies in Critically Ill Children

    Science.gov (United States)

    Thakkar, Nilay; Salerno, Sara; Hornik, Christoph P.; Gonzalez, Daniel

    2016-01-01

    Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs. PMID:27585904

  5. The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.

    Science.gov (United States)

    White, C Michael

    2017-03-01

    This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events. © 2016, The American College of Clinical Pharmacology.

  6. Human pharmacology for addiction medicine: From evidence to clinical recommendations.

    Science.gov (United States)

    Quednow, Boris B; Herdener, Marcus

    2016-01-01

    Substance use disorders (SUD) are complex and often chronic diseases with negative health outcomes and social consequences. Pharmacological treatment options for SUD can be separated in medications for (i) intoxication, (ii) withdrawal, and (iii) reduction of use together with relapse prevention. This chapter will focus on approved or clinically established pharmacological strategies suited to manage symptoms of withdrawal, and to reduce substance use or to promote abstinence. Hereby SUD involving alcohol, nicotine, stimulants, and opioids are primarily discussed as these substances are considered most harmful for both the individual and the society. Moreover, the pharmacotherapy of SUD related to the use of cannabis, benzodiazepines, and gamma-hydroxybutyrate is also briefly reviewed. Since most approved pharmacological treatment options show only moderate effect sizes especially in the long term, the development of new treatment strategies including new drugs, new combinations of available compounds, and biomarkers for response prediction is still warranted. © 2016 Elsevier B.V. All rights reserved.

  7. Phytochemistry, pharmacology, and clinical trials of Morus alba.

    Science.gov (United States)

    Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

    2016-01-01

    The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  8. 76 FR 38668 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-07-01

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General.... In response to feedback during the April 13, 2010, Advisory Committee for Pharmaceutical Science and...

  9. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-06-29

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

  10. 75 FR 11551 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-11

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... Pharmaceutical Science (OPS) on the regulatory challenges of drug-induced phospholipidosis (excessive...

  11. 78 FR 58315 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... continuous manufacturing for pharmaceutical products. Speakers from the Agency, academia, and industry will...

  12. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications.

    Science.gov (United States)

    Wuttke, W; Jarry, H; Christoffel, V; Spengler, B; Seidlová-Wuttke, D

    2003-05-01

    Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.

  13. Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor.

    Science.gov (United States)

    Iwamoto, Marian; Friedman, Evan J; Sandhu, Punam; Agrawal, Nancy G B; Rubin, Eric H; Wagner, John A

    2013-09-01

    Vorinostat is a histone deacetylase inhibitor that has demonstrated preclinical activity in numerous cancer models. Clinical activity has been demonstrated in patients with a variety of malignancies. Vorinostat is presently indicated for the treatment of patients with advanced cutaneous T cell lymphoma (CTCL). Clinical investigation is ongoing for therapy of other solid tumors and hematological malignancies either as monotherapy or in combination with other chemotherapeutic agents. This review summarizes the pharmacokinetic properties of vorinostat. Monotherapy pharmacokinetic data across a number of pharmacokinetic studies were reviewed, and data are presented. In addition, literature review was performed to obtain published Phase I and II pharmacokinetic combination therapy data to identify and characterize potential drug interactions with vorinostat. Pharmacokinetic data in special populations were also reviewed. The clinical pharmacology profile of vorinostat is favorable, exhibiting dose-proportional pharmacokinetics and modest food effect. There appear to be no major differences in the pharmacokinetics of vorinostat in special populations, including varying demographics and hepatic dysfunction. Combination therapy pharmacokinetic data indicate that vorinostat has a low propensity for drug interactions. Vorinostat's favorable clinical pharmacology and drug interaction profile aid in the ease of administration of vorinostat for the treatment of advanced CTCL and will be beneficial in continued assessment for other oncologic indications. Although a number of studies have been conducted to elucidate the detailed pharmacokinetic profile of vorinostat, more rigorous assessment of vorinostat pharmacokinetics, including clinical drug interaction studies, will be informative.

  14. Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality

    DEFF Research Database (Denmark)

    Brøsen, Kim; Andersen, Stig Ejdrup; Borregaard, Jeanett

    2016-01-01

    new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors...

  15. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  16. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

  17. 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.

  18. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

    DEFF Research Database (Denmark)

    Jung, Helene U; Frimodt-Møller, Poul C; Osther, Palle J

    2006-01-01

    We searched to review experimental and clinical trials concerning the capabilities of impacting on the ureteric and pelvic activity by means of pharmacological stimulation. Ureteropyeloscopy may cause high renal pelvic pressure. The normal pressure is in the range of 5-15 mmHg whereas pressure...... an increased risk of several complications related to endourological procedures including bleeding, perforation and infection. In other words, means by which intrarenal pressure could be lowered during endourological procedures might be beneficial with respect to clinical outcomes. In vitro experiments support...... systemic side effects. In vivo human studies are necessary to clarify the exact dose-response relationship and the degree of urothelial absorption of a drug before clinical use may be adopted....

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

    Science.gov (United States)

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

    2013-01-01

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

  20. Clinical pharmacology profile of care in Hepatology clinic

    Directory of Open Access Journals (Sweden)

    Talita Rocha Passos

    Full Text Available Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%, metformin 132 (26.8% and losartan 80 (16.3%. Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

  1. World Antimalarial Resistance Network (WARN IV: Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2007-09-01

    Full Text Available Abstract A World Antimalarial Resistance Network (WARN database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics. By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component

  2. Clinical and practical considerations in the pharmacologic management of narcolepsy.

    Science.gov (United States)

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Clinical pharmacology review of escitalopram for the treatment of depression.

    Science.gov (United States)

    Pastoor, Devin; Gobburu, Joga

    2014-01-01

    Depression is a serious and debilitating psychiatric condition with serious societal health and economic implications. Escitalopram , the S-enantiomer of racemic citalopram, is an effective treatment for major depressive disorder. This review covers the clinical pharmacology of escitalopram, with emphasis on regulatory approval. Its pharmacokinetics, pharmacodynamics and clinical efficacy for major depressive disorder are evaluated, along with data regarding safety and tolerability. Drug development of escitalopram was heavily guided by prior approval of citalopram. Select safety and efficacy studies for escitalopram in combination with supportive evidence from the results of prior citalopram studies allowed for regulatory approval for acute and maintenance claims in both adults and adolescents, while minimizing burden on the sponsor. Escitalopram has been shown to have better efficacy and safety profile than other selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs, including racemic citalopram. The first generic escitalopram was approved in 2012, along with Abbreviated New Drug Applications. The associated cost savings have helped reduce the burden of weighing the benefits of escitalopram over less-expensive alternatives.

  4. MR arthrography: pharmacology, efficacy and safety in clinical trials

    International Nuclear Information System (INIS)

    Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K.; Wegener, R.; Balzer, T.

    2003-01-01

    A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost the same

  5. Clinical Pharmacology of Furosemide in Neonates: A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2013-09-01

    Full Text Available Furosemide is the diuretic most used in newborn infants. It blocks the Na+-K+-2Cl− symporter in the thick ascending limb of the loop of Henle increasing urinary excretion of Na+ and Cl−. This article aimed to review the published data on the clinical pharmacology of furosemide in neonates to provide a critical, comprehensive, authoritative and, updated survey on the metabolism, pharmacokinetics, pharmacodynamics and side-effects of furosemide in neonates. The bibliographic search was performed using PubMed and EMBASE databases as search engines; January 2013 was the cutoff point. Furosemide half-life (t1/2 is 6 to 20-fold longer, clearance (Cl is 1.2 to 14-fold smaller and volume of distribution (Vd is 1.3 to 6-fold larger than the adult values. t1/2 shortens and Cl increases as the neonatal maturation proceeds. Continuous intravenous infusion of furosemide yields more controlled diuresis than the intermittent intravenous infusion. Furosemide may be administered by inhalation to infants with chronic lung disease to improve pulmonary mechanics. Furosemide stimulates prostaglandin E2 synthesis, a potent dilator of the patent ductus arteriosus, and the administration of furosemide to any preterm infants should be carefully weighed against the risk of precipitation of a symptomatic patent ductus arteriosus. Infants with low birthweight treated with chronic furosemide are at risk for the development of intra-renal calcifications.

  6. Clinical Pharmacology of Fentanyl in Preterm Infants. A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2015-06-01

    Full Text Available Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.

  7. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  8. 75 FR 10488 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  9. 76 FR 3912 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  10. 78 FR 42966 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-07-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  11. 77 FR 41790 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  12. 77 FR 42746 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  13. 78 FR 58314 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... session, the Office of Pharmaceutical Science and the Office of Compliance will discuss with the committee...

  14. 77 FR 1696 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-01-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  15. 75 FR 8368 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-02-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0067] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

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

    Science.gov (United States)

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

    2012-09-01

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

  17. Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues.

    Science.gov (United States)

    Schifano, Fabrizio; Albanese, Antonio; Fergus, Suzanne; Stair, Jackie L; Deluca, Paolo; Corazza, Ornella; Davey, Zoe; Corkery, John; Siemann, Holger; Scherbaum, Norbert; Farre', Magi'; Torrens, Marta; Demetrovics, Zsolt; Ghodse, A Hamid

    2011-04-01

    Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

  18. An Endocrine Pharmacology Course for the Clinically-Oriented Pharmacy Curriculum

    Science.gov (United States)

    Rahwan, Ralf G.

    1976-01-01

    In view of trends in clinical pharmacy education, the role of the traditional basic sciences has to be reassessed. An endocrine pharmacology course comprised of 49 clock-hours and open for professional undergraduate and graduate credit is described that blends basic and applied pharmacology. (LBH)

  19. A review of the pharmacology and clinical efficacy of brivaracetam

    Directory of Open Access Journals (Sweden)

    Klein P

    2018-01-01

    Full Text Available Pavel Klein,1 Anyzeila Diaz,2 Teresa Gasalla,3 John Whitesides4 1Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA; 2Neurology Patient Value Unit, UCB Pharma, Smyrna, GA, USA; 3Neurology Patient Value Unit, UCB Pharma, Monheim am Rhein, Germany; 4Asset Development, UCB Pharma, Raleigh, NC, USA Abstract: Brivaracetam (BRV; Briviact is a new antiepileptic drug (AED approved for adjunctive treatment of focal (partial-onset seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg and multiple (200–800 mg/day oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV. Keywords: brivaracetam, efficacy

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

    OpenAIRE

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

    2012-01-01

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

  1. Clinical Pharmacology of Kinase Inhibitors in Oncology : Personalized and Optimzed Dosing

    NARCIS (Netherlands)

    Verheijen, Remy B.

    2017-01-01

    Kinase inhibitors are an important category of molecularly targeted therapies used for cancer. Verheijen’s doctoral thesis describes several clinical pharmacological studies to optimize and personalize the treatment of cancer with kinase inhibitors, using pharmacokinetics, molecular imaging and

  2. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

    Science.gov (United States)

    Derendorf, H; Meltzer, E O

    2008-10-01

    Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

  3. The pharmacologic and clinical effects of medical cannabis.

    Science.gov (United States)

    Borgelt, Laura M; Franson, Kari L; Nussbaum, Abraham M; Wang, George S

    2013-02-01

    Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use. © 2013 Pharmacotherapy Publications, Inc.

  4. Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

    NARCIS (Netherlands)

    Dorlo, T.P.C.

    2013-01-01

    This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of

  5. Development of a Clinical Pharmacology Graduate Program at the University of Kentucky.

    Science.gov (United States)

    Blouin, Robert A.; And Others

    1994-01-01

    The structure, components, and anticipated outcomes of a University of Kentucky doctoral program in pharmacology are described. The program is designed to develop pharmacy-trained specialists who are interested in rigorous, intensive clinical experience, state-of-the-art coursework, and integrated laboratory-based and clinical dissertation…

  6. Clinical, molecular, and pharmacological aspects of FMR1 related disorders.

    Science.gov (United States)

    Pugin, A; Faundes, V; Santa María, L; Curotto, B; Aliaga, S; Salas, I; Soto, P; Bravo, P; Peña, M I; Alliende, M A

    2017-05-01

    Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Pharmacological basis and clinical evidence of dabigatran therapy

    Directory of Open Access Journals (Sweden)

    Redondo Santiago

    2011-12-01

    Full Text Available Abstract Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves.

  8. Preliminary clinical pharmacological investigations of tylosin and tiamulin in chickens.

    Science.gov (United States)

    Ziv, G

    1980-10-15

    The minimal inhibitory concentrations (MIC) of tiamulin and tylosin for mycoplasma, Gram-positive, and Gram-negative micro-organisms isolated from chickens were determinated by the agar dilution method. Median MIC values for tiamulin against Mycoplasma gallisepticum (0.05 microgram/ml) and Mycoplasma synoviae (0.10 microgram/ml) were 2 to 4 times lower than the corresponding values for tylosin. Tiamulin was also slightly more effective in vitro in inhibiting Escherichia coli, Pasteurella multocida, and beta-haemolytic streptococci than was tylosin. Groups of chicken were offered tiamulin medicated drinking water at rates of 125 and 250 mg/litre for 48 hours. Average serum tiamulin concentrations were 0.38 and 0.78 microgram/ml, respectively. When tylosin tartrate was added to the drinking water at 500 and 700 mg/litre, average serum drug levels were 0.12 and 0.17 microgram/ml, respectively. Tiamulin was 45% bound in chicken serum, as against 30% serum protein binding for tylosin. Correlations were made between free (non protein bound) serum drug levels and the MIC values of the two drugs. Such comparisons suggest that when tiamulin is given in the drinking water at rates of 125 to 250 mg/litre, better antimycoplasmal activity is to be expected in vivo than by giving tylosin tartrate in the drinking water at 500 to 700 mg/litre. Based on these data, no clinical efficacy of these dose rates can be expected in flocks infected by gram-negative micro-organisms such as E. coli or P. multocida. The tylosin tartrate rate of 500 to 700 mg/litre, may be clinical ineffective the treatment of Staphylococcus aureus infections.

  9. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Blom, M T; van Hoeijen, D A; Bardai, A

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA. ME......-reviewed journals and presented at relevant scientific symposia....

  10. Alpha radioisotopes Ac-225 and Bi-213: a production and labelling of antibodies and peptides for clinical use

    Energy Technology Data Exchange (ETDEWEB)

    Bruchertseifer, Frank, E-mail: frank.bruchertseifer@ec.europa.eu [European Commission, Joint Research Centre, Karlsruhe (Germany)

    2017-07-01

    Full text: In various preclinical and clinical works the potential of the alpha emitters {sup 225}Ac and {sup 213}Bi as therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases was demonstrated. Both alpha emitters are available with high specific activity from established radionuclide generators. Their favorable chemical and physical properties have led to the conduction of a large number of preclinical studies and several clinical trials, demonstrating the feasibility, safety and therapeutic efficacy of targeted alpha therapy with {sup 225}Ac and {sup 213}Bi. This presentation will give an overview about the methods for the production of {sup 225}Ac and {sup 213}Bi, the {sup 225}Ac/{sup 213}Bi radionuclide generator systems, labelling of peptides and antibodies with {sup 225}Ac and {sup 213}Bi and relevant in vivo and in vitro works. (author)

  11. Review of the pharmacology and clinical studies of micafungin

    Directory of Open Access Journals (Sweden)

    Alison M Bormann

    2009-12-01

    Full Text Available Alison M Bormann1, Vicki A Morrison21Division of Infectious Diseases, University of Minnesota, Minneapolis, MN, USA; 2Division of Hematology/Oncology and Infectious Disease, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Micafungin, like other members of the echinocandin class, has a unique mechanism of action that inhibits the synthesis of 1,3-β-D glucans in the fungal cell wall. It has been approved for treatment of esophageal candidiasis, invasive candidiasis including candidemia, and for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. Although efficacy and safety have also been demonstrated in pediatric populations, micafungin is approved for this indication in Europe and Japan, but not in the United States. It has demonstrated activity against Candida spp. including those that are azole-resistant as well as Aspergillus and a few other clinically important molds. It is administered intravenously as a once daily infusion and does not require dose adjustments for renal or moderate hepatic dysfunction. Its safety record, favorable tolerability profile, and few drug interactions make it an important agent for the treatment of invasive fungal infections.Keywords: micafungin, antifungal therapy, echinocandins, fungal infections, Candida, Aspergillus

  12. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

    Science.gov (United States)

    Pacifici, Gian M

    2016-01-01

    Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

  13. A review on Pharmacological and clinical aspects of Linum usitatissimum L.

    Science.gov (United States)

    Ansari, Ramin; Zarshenas, Mohammad Mehdi; Dadbakhsh, Amir Hossein

    2018-05-20

    Linum usitatissimum L., known as common Flax or linseed, from the family Linnaceae, has long been cultivated in different nations due to its applications in medicine and industry. The present study aims to collect nearly all available information about chemical constituents of Flax, as well as pharmacological properties and confirmed clinical usages of it. We searched through databases such as Scopus and PubMed for relevant literatures using the keywords: (Linum usitatissimum), (pharmacology) and (phytochemical) from the beginning to 13 Aug 2017. Nearly 60 relevant papers, relating to pharmacological and phytochemical constituent of L. usitatissimum were selected. According to our researches, various properties were attributed to L. usitatisimum including: antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, Antiprotozoal, insecticidal, Analgesic, anti-hyperlipidemia, Anti-hyperglycemic, Anti-tumor, wound healing and Feticidal activities. There were also many reports to the disease preventive and healing properties of the flax. Diseases like: GI disorders, cardiovascular, urogenital, respiratory diseases and some neurological syndromes were mentioned to be treated by Flax. The application of Flax in drug formulations was also investigated. Despite so much animal studies that have been accomplished, there haven't been enough clinical trials done on pharmacological properties of L. usitatissimum. Therefore this study could be considered as a concise and up to date overview for further facile studies and clinical trials over the valuable plant, L. usitatissimum. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. [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.

  15. A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students

    Science.gov (United States)

    Rosenbaum, Paul-Erik Lillholm; Mikalsen, Øyvind; Lygre, Henning; Solheim, Einar; Schjøtt, Jan

    2012-01-01

    Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components. PMID:23248716

  16. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Science.gov (United States)

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  17. Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

    2010-01-01

    The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Analysis of the Chemical, Pharmacological and Clinical Applications of Polygonum Cuspidatum

    Science.gov (United States)

    Guo, Chenyang; Bai, Ming; Miao, Mingsan; Miao, Yanyan

    2018-01-01

    Traditional Chinese medicine Polygonum cuspidatum widely used, the larger production, and in the clinical application of more, but the role played by the role of different roles are also different. By reviewing the relevant literatures in recent years, the chemical constituents and pharmacological effects of Polygonum cuspidatum were sorted and summarized, and the role of Polygonum cuspidatum was analyzed, and the function of Polygonum cuspidatum was explored to find out the role of Polygonum cuspidatum in compatibility. Application law. Which can not only study the medicinal mechanism of Polygonum cuspidatum, but also provide the theoretical basis for the medicinal development, clinical treatment and comprehensive utilization of Polygonum cuspidatum.

  19. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Discovery of Mixed Pharmacology Melanocortin-3 Agonists and Melanocortin-4 Receptor Tetrapeptide Antagonist Compounds (TACOs) Based on the Sequence Ac-Xaa1-Arg-(pI)DPhe-Xaa4-NH2.

    Science.gov (United States)

    Doering, Skye R; Freeman, Katie T; Schnell, Sathya M; Haslach, Erica M; Dirain, Marvin; Debevec, Ginamarie; Geer, Phaedra; Santos, Radleigh G; Giulianotti, Marc A; Pinilla, Clemencia; Appel, Jon R; Speth, Robert C; Houghten, Richard A; Haskell-Luevano, Carrie

    2017-05-25

    The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for weight management therapies, with a preponderance of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa 1 -Arg-(pI)DPhe-Xaa 4 -NH 2 ] is reported. The scaffold was derived from results obtained from a MC3R mixture-based positional scanning campaign. From these results, a set of 48 tetrapeptides were designed and pharmacologically characterized at the mouse melanocortin-1, -3, -4, and -5 receptors. This resulted in the serendipitous discovery of nine compounds that were MC3R agonists (EC 50 DPhe-Tic-NH 2 ], 1 [Ac-His-Arg-(pI)DPhe-Tic-NH 2 ], and 41 [Ac-Arg-Arg-(pI)DPhe-DNal(2')-NH 2 ] were more potent (EC 50 DPhe-Arg-Trp-NH 2 . This template contains a sequentially reversed "Arg-(pI)DPhe" motif with respect to the classical "Phe-Arg" melanocortin signaling motif, which results in pharmacology that is first-in-class for the central melanocortin receptors.

  1. [History of clinical pharmacology in France: adaptation, evaluation, defense and illustration of drug in France 1978-1981].

    Science.gov (United States)

    Montastruc, Paul

    2014-01-01

    This text illustrates some unknown aspects of the history and beginnings of clinical pharmacology in France in the late 1970s and early 1980s From the current situation, development and objectives of clinical pharmacology are recalled as well as obstacles necessary to overcome to change the paradigm in the field of drug evaluation and appropriate use in France. The text recalls this important moment where French medicine and medical pharmacology entered the modern era. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  2. Overview of clinical efficacy and safety of pharmacologic strategies for blood conservation.

    Science.gov (United States)

    Levy, Jerrold H

    2005-09-15

    The pharmacologic management of hemostasis in patients undergoing surgery with cardiopulmonary bypass is discussed. Nearly 45 studies involving 7,000 patients have reported efficacy of aprotinin in blood conservation. Both in primary coronary artery bypass graft (CABG) surgeries and in repeat surgeries, aprotinin treatment significantly reduces the incidence of blood transfusions and the number of units of blood transfused. These effects have been observed for red blood cell, platelet, and other blood products. The safety of aprotinin treatment has been extensively evaluated in randomized clinical trials, in postmarketing databases, and in systematic reviews of the literature. Overall, data do not indicate that aprotinin treatment increases mortality, myocardial infarction, or renal failure. These findings are supported by the results of a recent meta-analysis of 35 studies in patients undergoing CABG surgery. In addition, the meta-analysis suggests that aprotinin treatment was associated with a reduced incidence of stroke and a trend toward a reduced incidence of atrial fibrillation. Although lysine analogs, desmopressin, and recombinant factor VIIa are sometimes used to reduce bleeding, only aprotinin is indicated for use during CABG surgery. The future of cardiac surgery will be marked by an increasingly complex, high-risk group of patients and a greater need for multiple pharmacologic options for reducing bleeding. Pharmacologic approaches that attenuate the activation of the hemostatic system and inflammation need to be employed to decrease coagulopathies and the need for allogeneic blood administration.

  3. Clinical pathways and management of antithrombotic therapy in patients with acute coronary syndrome (ACS): a Consensus Document from the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Cardiology (SIC), Italian Society of Emergency Medicine (SIMEU) and Italian Society of Interventional Cardiology (SICI-GISE)

    Science.gov (United States)

    Colivicchi, Furio; Gulizia, Michele Massimo; Pugliese, Francesco Rocco; Ruggieri, Maria Pia; Musumeci, Giuseppe; Cibinel, Gian Alfonso; Romeo, Francesco

    2017-01-01

    Abstract Antiplatelet therapy is the cornerstone of the pharmacologic management of patients with acute coronary syndrome (ACS). Over the last years, several studies have evaluated old and new oral or intravenous antiplatelet agents in ACS patients. In particular, research was focused on assessing superiority of two novel platelet ADP P2Y12 receptor antagonists (i.e., prasugrel and ticagrelor) over clopidogrel. Several large randomized controlled trials have been undertaken in this setting and a wide variety of prespecified and post-hoc analyses are available that evaluated the potential benefits of novel antiplatelet therapies in different subsets of patients with ACS. The aim of this document is to review recent data on the use of current antiplatelet agents for in-hospital treatment of ACS patients. In addition, in order to overcome increasing clinical challenges and implement effective therapeutic interventions, this document identifies all potential specific care pathway for ACS patients and accordingly proposes individualized therapeutic options. PMID:28751840

  4. Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?

    Directory of Open Access Journals (Sweden)

    Jem D. Lane

    2017-11-01

    Full Text Available Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. In this review, we look at some of the lessons to be learned from approaches to arrhythmia prediction in patients, clinical trials of drugs used in the treatment of arrhythmias, and the implications for the design of pre-clinical safety pharmacology testing.

  5. Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

    Science.gov (United States)

    DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

    2013-10-01

    Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P Kruskal-Wallis P < 0.001).

  6. Differential clinical pharmacology of rolapitant in delayed chemotherapy-induced nausea and vomiting (CINV

    Directory of Open Access Journals (Sweden)

    Rashad N

    2017-03-01

    Full Text Available Noha Rashad,1 Omar Abdel-Rahman2 1Medical Oncology Department, Maadi Armed Forces Hospital, 2Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2–4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours; this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug–drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. The clinical efficacy of rolapitant was studied in two phase III trials in highly emetogenic chemotherapy and in one clinical trial in moderately emetogenic chemotherapy. The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication in the delayed phase (>24–120 hours after chemotherapy. In comparison to granisetron (10 µg/kg intravenously and dexamethasone (20 mg orally on day 1, and dexamethasone (8 mg orally twice daily on days 2–4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV among currently available guidelines, and exploring the future directions of CINV management. Keywords: nausea, vomiting, chemotherapy, rolapitant, CINV

  7. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  8. The mollusks in zootherapy: traditional medicine and clinical-pharmacological importance

    Directory of Open Access Journals (Sweden)

    Eraldo Medeiros Costa Neto

    2006-09-01

    Full Text Available The use of animals as sources of medicines is a cross-cultural phenomenon that is historically ancient and geographically widespread. This article reviews the use of mollusks in traditional medicine and discusses the clinical and pharmacological importance of these invertebrates. The roles that mollusks play in folk practices related to the healing and/or prevention of illnesses have been recorded in different social-cultural contexts worldwide. The clinical and therapeutic use of compounds coming from different species of mollusks is recorded in the literature. The chemistry of natural products provided by oysters, mussels, clams, sluggards, and snails has been substantially investigated, but the majority of these studies have focused on the subclasses Opistobranchia and Prosobranchia. Research into the knowledge and practices of folk medicine makes possible a better understanding of the interaction between human beings and the environment, in addition to allowing the elaboration of suitable strategies for the conservation of natural resources.

  9. CLINICAL AND PHARMACOLOGICAL PECULIARITIES OF CETIRIZINE USE FOR THE THERAPY OF ALLERGIC DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu. G. Levina

    2014-01-01

    Full Text Available The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis. 

  10. Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

    Science.gov (United States)

    Norelli, M; Casucci, M; Bonini, C; Bondanza, A

    2016-01-01

    Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors. Copyright © 2015. Published by Elsevier B.V.

  11. Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Calapai, Fabrizio; Mancari, Ferdinando; Giofrè, Salvatore Vincenzo; Gangemi, Sebastiano; Calapai, Gioacchino

    2015-05-01

    Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Methamphetamine: An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

    Science.gov (United States)

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

    Background Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research. PMID:25176528

  13. Carthami flos: a review of its ethnopharmacology, pharmacology and clinical applications

    Directory of Open Access Journals (Sweden)

    Yanhua Tu

    Full Text Available ABSTRACTCarthami flos, the dried floret of Carthamus tinctorius L., Asteraceae (safflower, has been widely used in traditional Chinese medicine to treat a broad range of ailments, such as coronary heart disease, angina pectoris, gynecologic disease, stroke, and hypertension. However, although several studies on Carthami flos have been done consecutively, the results are usually scattered across various documents. This review aims to provide up-to-date information on the traditional uses, pharmacology, clinical applications, and toxicology of Carthami flos in China and thereby to provide a basis for further investigation of its use to treat dissimilar diseases. Various ethnomedical uses of Carthami flos have been documented in many ancient Chinese books. Crude extracts and isolated compounds from Carthami flos show a broad range of pharmacological properties, such as protective effects on brain tissue, on osteoblasts, and in myocardial ischemia, as well as anti-inflammatory, antithrombotic, antitumor, and antidiabetic activities. To date, safflower and safflor yellow injections have been used to treat coronary heart disease, chronic pulmonary heart disease, cerebrovascular diseases, orthopedic diseases, and diabetes mellitus. Regarding the toxicology of Carthami flos, among the side effects that have been observed are allergic reaction, spermatogenetic failure, fatty liver, and nephrotoxicity.

  14. Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence.

    Science.gov (United States)

    Singh, Anamika; Tala, Srinivasa R; Flores, Viktor; Freeman, Katie; Haskell-Luevano, Carrie

    2015-05-14

    The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β(3)-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β(3)-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β(3)hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.

  15. Synthesis and Pharmacology of α/β3-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence

    Science.gov (United States)

    2015-01-01

    The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β3-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β3-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β3hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands. PMID:26005535

  16. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  17. CLINICAL-PHARMACOLOGICAL VALUE OF TREATMENT EFFICIENCY OF BHP-PATIENTS BY ANTITHROMBOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    A.A. Svistunov

    2007-09-01

    Full Text Available Patients with BHP need in pharmacological treatment of thrombosis the most often in the first 3 cases because has dysfunctions of platelets and coagulation. According to results of analysis of efficiency antithrombotic therapy in BHP-patients confirmed clinical and biochemical influence antithrombotic therapy by Ticlid 250 mg twice on the day in comparison with Aspirin 100 mg and Dipiridomol 25 mg on the basic therapy of the BHP by Permixon 160 mg. The received results have had statistically meant differences. Manifestation of BHP and value QOL and others urodynamic complications most often appear on the basic specific monotherapy of BHP and lost after antithrombotic therapy for 1-3 months. The important complications of antithrombotic therapy of BHP-patients did not observe.

  18. Clinical inertia in the pharmacological management of hypertension: A systematic review and meta-analysis.

    Science.gov (United States)

    Milman, Tal; Joundi, Raed A; Alotaibi, Naif M; Saposnik, Gustavo

    2018-06-01

    Clinical Inertia is defined as "failure of health care providers to initiate or intensify therapy according to current guidelines". This phenomenon is gaining increasing attention as a major cause of clinicians' failure to adequately manage hypertension, thus leading to an increased incidence of cardiovascular events. We performed a systematic review and meta-analysis of randomized controlled trials to determine whether interventions aimed at reducing clinical inertia in the pharmacological treatment of hypertension improve blood pressure (BP) control. MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched from the start of their database until October 3, 2017 for the MESH terms "Hypertension" or "Blood Pressure", their subheadings, and the keywords "Therapeutic Inertia" or "Clinical Inertia". Studies were included if they addressed pharmacologic hypertension management, clinical inertia, were randomized controlled trials, reported an outcome describing prescriber behavior, and were available in English. Data for the included studies was extracted by two independent observers. Quality of studies was analyzed using the Cochrane Risk of Bias Assessment. Data was pooled for statistical analysis using both fixed- and random-effects models. The primary study outcome was the percentage of patients achieving blood pressure control as defined by the Joint National Committee guidelines or study authors. Of 474 citations identified, ten met inclusion criteria comprising a total of 26,871 patients, and eight were selected for meta-analysis. Interventions included Physician Education, Physician Reminders, Patient Education, Patient Reminders, Ambulatory BP Monitoring, Digital Medication Offerings, Physician Peer Visits, and Pharmacist-led Counselling. Pooled event rates revealed more patients with controlled BP in the intervention group versus control (55%, 95% CI 46-63% versus 45%, 95% CI 37-53%) and interventions significantly improved the odds of BP

  19. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  20. Pharmacological profile of β3-adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome

    NARCIS (Netherlands)

    Igawa, Yasuhiko; Michel, Martin C.

    2013-01-01

    β(3)-Adrenoceptor agonists are an emerging drug class for the treatment of the overactive bladder syndrome, and clinical proof-of-concept data have been obtained for three representatives of this class, mirabegron, ritobegron, and solabegron. We review here the pharmacological profile of these three

  1. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

    DEFF Research Database (Denmark)

    Roessner, Veit; Plessen, Kerstin J; Rothenberger, Aribert

    2011-01-01

    provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary...

  2. Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical pharmacology.

    Science.gov (United States)

    Ekelund, S; Nygren, P; Larsson, R

    2001-05-15

    The pharmacology and clinical application of three guanidino-containing compounds are reviewed in this commentary with special focus on a new member of this group of drugs, CHS 828 [N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridylguanidine]. m-Iodobenzylguanidine (MIBG) and methylglyoxal bis(guanylhydrazone) (MGBG) have been extensively studied, preclinically as well as clinically, and have established use as anticancer agents. MIBG has structural similarities to the neurotransmitter, norepinephrine, and MGBG is a structural analog of the natural polyamine spermidine. CHS 828 is a pyridyl cyanoguanidine newly recognized as having cytotoxic effects when screening antihypertensive compounds. Apart from having the guanidino groups in common, there are many differences between these drugs in both structure and their mechanisms of action. However, they all inhibit mitochondrial function, a seemingly unique feature among chemotherapeutic drugs. In vitro in various cell lines and primary cultures of patient tumor cells and in vivo in various tumor models, CHS 828 has cytotoxic properties unlike any of the standard cytotoxic drugs with which it has been compared. Among these are non-cross-resistance to standard drugs and pronounced activity in tumor models acknowledged to be highly drug-resistant. Similar to MIBG, CHS 828 induces an early increase in extracellular acidification, due to stimulation of the glycolytic flux. Furthermore, ATP levels decrease, and the syntheses of DNA and protein are shut off after approximately 30 hr of exposure, indicating active cell death. CHS 828 is now in early clinical trials, the results of which are eagerly awaited.

  3. Differential pharmacology and clinical utility of rolapitant in chemotherapy-induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Rapoport BL

    2017-02-01

    Full Text Available Bernardo Leon Rapoport The Medical Oncology Centre of Rosebank, Johannesburg, South Africa Abstract: Chemotherapy-induced nausea and vomiting (CINV is a debilitating side effect of many cytotoxic chemotherapy regimens. CINV typically manifests during two well-defined time periods (acute and delayed phases. The acute phase is the first 24 hours after chemotherapy and is largely managed with 5-hydroxytryptamine 3 receptor antagonists. The delayed phase, a 5-day at-risk period during which patients are not often in direct contact with their health care provider, remains a significant unmet medical need. Neurokinin-1 (NK-1 receptor antagonists have demonstrated protection against acute and delayed CINV in patients treated with highly emetogenic chemotherapy and moderately emetogenic chemotherapy when used in combination with a 5-hydroxytryptamine 3 receptor antagonist and dexamethasone. Furthermore, recent data indicate that this protection is maintained over multiple treatment cycles. Rolapitant, a selective and long-acting NK-1 receptor antagonist, is approved as oral formulation for the prevention of delayed CINV in adults. This review discusses the differential pharmacology and clinical utility of rolapitant in preventing CINV compared with other NK-1 receptor antagonists. Keywords: antiemetics, highly emetogenic chemotherapy, moderately emetogenic chemotherapy, delayed chemotherapy-induced nausea and vomiting, emesis, neurokinin-1 receptor antagonists

  4. [Clinical subtypes of essential tremor and their electrophysiological and pharmacological differences].

    Science.gov (United States)

    Koguchi, Y; Nakajima, M; Kawamura, M; Hirayama, K

    1995-02-01

    We divided 19 patients with essential tremor into two subtypes according to clinical characteristics of the tremor. Ten patients had pure postural tremor distributed in the hand(s), head, and face (group A). Nine patients had tremor extending to the voice or leg(s), associated with resting tremor and/or hyperkinesie volitionnelle of the hand(s) (group B). Their ages, the age of onset, and the duration of illness were not different between the two groups. Electrophysiologically, the tremor of group A patients had higher frequencies than that of group B patients, and had synchronized activities for antagonistic muscles. Four of group B patients had reciprocal antagonistic activities of the tremor. Inactive phase of tremor induced by an electrically-evoked muscle twitch was invariably within the range of the physiological silent period for group A patients, and prolonged beyond the range for four of group B patients. Pharmacologically, 78% of group A patients responded well to beta-blocker, which was effective for 25% of group B patients. Sixty per cent of beta-blocker-resistant group B patients responded well to phenobarbital. In conclusion, a peripheral mechanism, presumably beta-adrenergic drive, is important for the tremor in group A patients, while central pathogenic mechanisms are more important for the tremor of group B patients.

  5. Avanafil for erectile dysfunction in elderly and younger adults: differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Katz EG

    2014-08-01

    Full Text Available Eric G Katz,1 Ronny BW Tan,2 Daniel Rittenberg,1 Wayne J Hellstrom3 1Tulane University School of Medicine, New Orleans, LA, USA; 2Department of Urology, Tan Tock Seng Hospital, Singapore; 3Section of Andrology, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA Abstract: The treatment modalities of erectile dysfunction range from oral pharmacotherapy to intracavernosal injections, intraurethral pellets, vacuum erectile devices, and the surgical option of penile prosthesis insertion. Oral phosphodiesterase 5 inhibitors still remain the preferred treatment for patients since they are the least invasive, not to mention that they can be prescribed by non-urologists. Due to these factors, there has been development of newer drugs with fewer side effects. This is a review of the second generation phosphodiesterase 5 inhibitor, avanafil, looking into its pharmacology as well as its clinical utility. Avanafil's faster onset and shorter duration of action has made it preferred as compared to other PDE5 inhibitors for patients with multiple comorbidities. Keywords: phosphodiesterase 5 inhibitors, impotence, sildenafil, sexual dysfunction, nitric oxide

  6. The retinoids. A review of their clinical pharmacology and therapeutic use.

    Science.gov (United States)

    Orfanos, C E; Ehlert, R; Gollnick, H

    1987-10-01

    With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

  7. Non-pharmacological modification of endothelial function: An important lesson for clinical practice

    Directory of Open Access Journals (Sweden)

    Monika Szulińska

    2018-03-01

    The impact of endothelial function in the complex pathology of cardiovascular diseases reflects a number of scientific proofs showing favorable effects of non-pharmacological interventions in endothelial dysfunction treatment.

  8. Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis.

    Science.gov (United States)

    Hourcade-Potelleret, F; Laporte, S; Lehnert, V; Delmar, P; Benghozi, Renée; Torriani, U; Koch, R; Mismetti, P

    2015-06-01

    Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. To assess alternative methods to predict clinical response of CETP inhibitors. Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. 51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. 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 

  10. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

    Directory of Open Access Journals (Sweden)

    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  11. Bringing stability to the COPD patient: clinical and pharmacological considerations for frequent exacerbators

    Science.gov (United States)

    Gulati, Swati

    2017-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A “frequent exacerbator” is a sub-phenotype of COPD that is defined as an individual who experiences ≥2 moderate to severe exacerbations per year. This distinct subgroup has higher mortality and account for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for utilizing combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: 1) maximizing bronchodilation, 2) reducing inflammation, and 3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies include combination long acting muscarinic agents (LAMA) plus long acting beta agonists (LABA) show promising results compared to monotherapy or LABA inhaled corticosteroid (ICS) combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase (PDE4) inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on identification of various subtypes or “endotypes” and targeting therapies based on their pathophysiology. This review aims to describe the impact of AECOPD, challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these

  12. Pharmacological and clinical dilemmas of prescribing in co-morbid adult attention-deficit/hyperactivity disorder and addiction

    Science.gov (United States)

    Pérez de los Cobos, José; Siñol, Núria; Pérez, Víctor; Trujols, Joan

    2014-01-01

    The present article reviews whether available efficacy and safety data support the pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD) in patients with concurrent substance use disorders (SUD). Arguments for and against treating adult ADHD with active SUD are discussed. Findings from 19 large open studies and controlled clinical trials show that the use of atomoxetine or extended-release methylphenidate formulations, together with psychological therapy, yield promising though inconclusive results about short term efficacy of these drugs in the treatment of adult ADHD in patients with SUD and no other severe mental disorders. However, the efficacy of these drugs is scant or lacking for treating concurrent SUD. No serious safety issues have been associated with these drugs in patients with co-morbid SUD-ADHD, given their low risk of abuse and favourable side effect and drug–drug interaction profile. The decision to treat adult ADHD in the context of active SUD depends on various factors, some directly related to SUD-ADHD co-morbidity (e.g. degree of diagnostic uncertainty for ADHD) and other factors related to the clinical expertise of the medical staff and availability of adequate resources (e.g. the means to monitor compliance with pharmacological treatment). Our recommendation is that clinical decisions be individualized and based on a careful analysis of the advantages and disadvantages of pharmacological treatment for ADHD on a case-by-case basis in the context of active SUD. PMID:23216449

  13. Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure.

    Science.gov (United States)

    Pacifici, Gian Maria

    2013-10-01

    Indomethacin is a non-steroidal anti-inflammatory drug that is a potent inhibitor of prostaglandin E(2) synthesis. After birth, the ductus arteriosus closes spontaneously within 2-4 days in term infants. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. Prostaglandin E(2) has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. In preterm infants with respiratory distress syndrome, the ductus arteriosus fails to close (patent ductus arteriosus [PDA]) because the concentration of prostaglandin E2 is relatively high. PDA occurs in more than 70 % of neonates weighing less than 1,500 g at birth. The aim of this article was to review the published data on the clinical pharmacology of indomethacin in preterm infants in order to provide a critical analysis of the literature and a useful tool for physicians. The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines and February 2012 was the cutoff point. A remarkable interindividual variability was observed for the half-life (t(½)), clearance (CL), and volume of distribution (V(d)) of indomethacin. Prophylactic indomethacin consists of a continuous infusion of low levels of indomethacin and may be useful in preterm infants. Extremely preterm infants are less likely to respond to indomethacin. Infants with a postnatal age of 2 months do not respond to treatment with indomethacin. Indomethacin has several adverse effects, the most common of which is renal failure. An increase in serum creatinine of ≥0.5 % mg/dL after indomethacin was observed in about 10-15 % of the patients and creatinine returns to a normal level about 1 week after cessation of therapy. Indomethacin should be administered intravenously by syringe pump for at least 30 min to minimize adverse effects on cerebral, gastrointestinal, and renal blood flow velocities. A

  14. Blended learning for reinforcing dental pharmacology in the clinical years: A qualitative analysis.

    Science.gov (United States)

    Eachempati, Prashanti; Kiran Kumar, K S; Sumanth, K N

    2016-10-01

    Blended learning has become the method of choice in educational institutions because of its systematic integration of traditional classroom teaching and online components. This study aims to analyze student's reflection regarding blended learning in dental pharmacology. A cross-sectional study was conducted in Faculty of Dentistry, Melaka-Manipal Medical College among 3 rd and 4 th year BDS students. A total of 145 dental students, who consented, participate in the study. Students were divided into 14 groups. Nine online sessions followed by nine face-to-face discussions were held. Each session addressed topics related to oral lesions and orofacial pain with pharmacological applications. After each week, students were asked to reflect on blended learning. On completion of 9 weeks, reflections were collected and analyzed. Qualitative analysis was done using thematic analysis model suggested by Braun and Clarke. The four main themes were identified, namely, merits of blended learning, skill in writing prescription for oral diseases, dosages of drugs, and identification of strengths and weakness. In general, the participants had a positive feedback regarding blended learning. Students felt more confident in drug selection and prescription writing. They could recollect the doses better after the online and face-to-face sessions. Most interestingly, the students reflected that they are able to identify their strength and weakness after the blended learning sessions. Blended learning module was successfully implemented for reinforcing dental pharmacology. The results obtained in this study enable us to plan future comparative studies to know the effectiveness of blended learning in dental pharmacology.

  15. Incretin-based therapies– review of the physiology, pharmacology and emerging clinical experience

    DEFF Research Database (Denmark)

    Martin, JH; Deacon, Carolyn F.; Gorrell, MD

    2011-01-01

    in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4...

  16. Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry.

    Science.gov (United States)

    Donato, Leslie J; Lueke, Alan; Kenyon, Stacy M; Meeusen, Jeffrey W; Camilleri, Michael

    2018-02-01

    Imbalance of bile acids (BA) homeostasis in the gastrointestinal tract can lead to chronic diarrhea or constipation when BA in the colon are in excess or low, respectively. Since both disturbances of bowel function can result from other etiologies, identifying BA imbalance is important to tailor treatment strategies. Serum concentrations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4), a precursor in bile acid synthesis, reflect BA homeostasis. Here we describe a method to accurately measure serum 7aC4 and evaluate the clinical utility in patients with diarrhea or constipation phenotypes. Serum 7aC4 is measured after acetonitrile protein precipitation using C18 liquid chromatography, tandem mass spectrometry, and deuterium-labeled 7aC4 internal standard. Assay performance including linearity, precision, and accuracy was assessed using waste serum samples. The reference interval was established in healthy individuals without BA-altering conditions or medications. Clinical performance was assessed in patients with irritable bowel syndrome. The method precisely and accurately measured 7aC4 in human serum from 1.4-338ng/mL with no ion suppression or interference from related 7-keto-cholesterol. Central 95th percentile reference interval was 2.5-63.2ng/mL. Lower serum 7aC4 was found in patients with constipation with sensitivity/specificity of 79%/55% compared to healthy controls. Higher 7aC4 was found in patients with bile acid diarrhea (BAD) compared to those without BAD with sensitivity/specificity of 82%/53%. We have developed a sensitive and precise assay for measuring the concentration of 7aC4 in serum. The assay can be used to screen for diarrhea caused by bile acid malabsorption. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Finite element model predicts current density distribution for clinical applications of tDCS and tACS

    Directory of Open Access Journals (Sweden)

    Toralf eNeuling

    2012-09-01

    Full Text Available Transcranial direct current stimulation (tDCS has been applied in numerous scientific studies over the past decade. However, the possibility to apply tDCS in therapy of neuropsychiatric disorders is still debated. While transcranial magnetic stimulation (TMS has been approved for treatment of major depression in the United States by the Food and Drug Administration (FDA, tDCS is not as widely accepted. One of the criticisms against tDCS is the lack of spatial specificity. Focality is limited by the electrode size (35 cm2 are commonly used and the bipolar arrangement. However, a current flow through the head directly from anode to cathode is an outdated view. Finite element (FE models have recently been used to predict the exact current flow during tDCS. These simulations have demonstrated that the current flow depends on tissue shape and conductivity. Toface the challenge to predict the location, magnitude and direction of the current flow induced by tDCS and transcranial alternating current stimulation (tACS, we used a refined realistic FE modeling approach. With respect to the literature on clinical tDCS and tACS, we analyzed two common setups for the location of the stimulation electrodes which target the frontal lobe and the occipital lobe, respectively. We compared lateral and medial electrode configuration with regard to theirusability. We were able to demonstrate that the lateral configurations yielded more focused stimulation areas as well as higher current intensities in the target areas. The high resolution of our simulation allows one to combine the modeled current flow with the knowledge of neuronal orientation to predict the consequences of tDCS and tACS. Our results not only offer a basis for a deeper understanding of the stimulation sites currently in use for clinical applications but also offer a better interpretation of observed effects.

  18. Treatment of post-partum depression: a review of clinical, psychological and pharmacological options

    Directory of Open Access Journals (Sweden)

    Elizabeth Fitelson

    2010-12-01

    Full Text Available Elizabeth Fitelson1, Sarah Kim4, Allison Scott Baker3, Kristin Leight21Director, 2Attending Psychiatrist, TheWomen's Program, 3Child and Adolescent Psychiatry Fellow, Division of Child Psychiatry, 4PGY-I Resident in Psychiatry, Department of Psychiatry, Columbia University Medical Center, New York, NY, USAAbstract: Postpartum depression (PPD is a common complication of childbearing, and has increasingly been identified as a major public health problem. Untreated maternal depression has multiple potential negative effects on maternal-infant attachment and child development. Screening for depression in the perinatal period is feasible in multiple primary care or obstetric settings, and can help identify depressed mothers earlier. However, there are multiple barriers to appropriate treatment, including concerns about medication effects in breastfeeding infants. This article reviews the literature and recommendations for the treatment of postpartum depression, with a focus on the range of pharmacological, psychotherapeutic, and other non-pharmacologic interventions. Keywords: postpartum depression, postnatal depression, lactation, antidepressant, hormone therapy, psychotherapy, bright light therapy, omega-3

  19. Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide

    Directory of Open Access Journals (Sweden)

    Thanasekaran Jayakumar

    2013-01-01

    Full Text Available Andrographis paniculata (Burm. F Nees, generally known as “king of bitters,” is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF-κB activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds.

  20. Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide

    Science.gov (United States)

    Jayakumar, Thanasekaran; Hsieh, Cheng-Ying; Lee, Jie-Jen; Sheu, Joen-Rong

    2013-01-01

    Andrographis paniculata (Burm. F) Nees, generally known as “king of bitters,” is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF-κB activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds. PMID:23634174

  1. A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Kim Lawson

    2017-05-01

    Full Text Available Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation. Several of the actions of amitriptyline on multiple nociceptive and sensory processes at central and peripheral locations have the potential to act cumulatively to suppress the characteristic symptoms of fibromyalgia. Greater understanding of the role of these mechanisms of action of amitriptyline could provide further clues to the pathophysiology of fibromyalgia and to a preferable pharmacological profile for future drug development.

  2. A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia

    Science.gov (United States)

    Lawson, Kim

    2017-01-01

    Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ) score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation. Several of the actions of amitriptyline on multiple nociceptive and sensory processes at central and peripheral locations have the potential to act cumulatively to suppress the characteristic symptoms of fibromyalgia. Greater understanding of the role of these mechanisms of action of amitriptyline could provide further clues to the pathophysiology of fibromyalgia and to a preferable pharmacological profile for future drug development. PMID:28536367

  3. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Yue ePei

    2016-04-01

    Full Text Available Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the classical biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA, norepinephrine, epinephrine, serotonin (5-HT and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS, and hence referred to as trace amines (TAs, are now recognized to play significant neurophysiological and behavioural functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1, a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signalling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson’s disease, schizophrenia, mood disorders and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  4. Evaluation of a filmed clinical scenario as a teaching resource for an introductory pharmacology unit for undergraduate health students: A pilot study.

    Science.gov (United States)

    East, Leah; Hutchinson, Marie

    2015-12-01

    Simulation is frequently being used as a learning and teaching resource for both undergraduate and postgraduate students, however reporting of the effectiveness of simulation particularly within the pharmacology context is scant. The aim of this pilot study was to evaluate a filmed simulated pharmacological clinical scenario as a teaching resource in an undergraduate pharmacological unit. Pilot cross-sectional quantitative survey. An Australian university. 32 undergraduate students completing a healthcare degree including nursing, midwifery, clinical science, health science, naturopathy, and osteopathy. As a part of an undergraduate online pharmacology unit, students were required to watch a filmed simulated pharmacological clinical scenario. To evaluate student learning, a measurement instrument developed from Bloom's cognitive domains (knowledge, comprehension, application, analysis, synthesis and evaluation) was employed to assess pharmacological knowledge conceptualisation and knowledge application within the following fields: medication errors; medication adverse effects; medication interactions; and, general pharmacology. The majority of participants were enrolled in an undergraduate nursing or midwifery programme (72%). Results demonstrated that the majority of nursing and midwifery students (56.52%) found the teaching resource complementary or more useful compared to a lecture although less so compared to a tutorial. Students' self-assessment of learning according to Bloom's cognitive domains indicated that the filmed scenario was a valuable learning tool. Analysis of variance indicated that health science students reported higher levels of learning compared to midwifery and nursing. Students' self-report of the learning benefits of a filmed simulated clinical scenario as a teaching resource suggest enhanced critical thinking skills and knowledge conceptualisation regarding pharmacology, in addition to being useful and complementary to other teaching and

  5. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  7. Prescribing knowledge in the light of undergraduate clinical pharmacology and therapeutics teaching in India: views of first-year postgraduate students

    Directory of Open Access Journals (Sweden)

    Upadhyaya P

    2012-06-01

    Full Text Available Prerna Upadhyaya,1 Vikas Seth,2 Monika Sharma,1 Mushtaq Ahmed,1 Vijay Vasant Moghe,1 Zafar Yab Khan,1 Vinay Kumar Gupta,1 Shipra Vikram Jain,1 Utkarsh Soni,1 Manohar Bhatia,1 Kumar Abhijit,1 Jaswant Goyal11Department of Pharmacology, Mahatma Gandhi Medical College, Jaipur, 2Department of Pharmacology, Hind Institute of Medical Sciences, Lucknow, IndiaObjectives: The study aimed to review the prescribing knowledge of first-year postgraduate doctors in a medical college in India, using the principles of good prescribing, to suggest strategies to improve rational prescribing, and to recommend what curriculum planners can do to accomplish this objective.Methods: Fifty first-year postgraduate doctors were asked to fill in a structured questionnaire that sought information regarding their undergraduate training in clinical pharmacology and therapeutics, prescribing habits, and commonly consulted drug information sources. Also, the questionnaire assessed any perceived deficiencies in their undergraduate clinical pharmacology teaching and sought feedback regarding improvement in the teaching.Results: Eighty-eight percent of residents said that they were taught prescription writing in undergraduate pharmacology teaching; 48% of residents rated their prescribing knowledge at graduation as average, 28% good, 4% excellent, 14% poor, and 4% very poor; 58% felt that their undergraduate training did not prepare them to prescribe safely, and 62% felt that their training did not prepare them to prescribe rationally. Fifty-eight percent of residents felt that they had some specific problems with writing a prescription during their internship training, while 92% thought that undergraduate teaching should be improved. Their suggestions for improving teaching methods were recorded.Conclusions: This study concludes that efforts are needed to develop a curriculum that encompasses important aspects of clinical pharmacology and therapeutics along with incorporation of

  8. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S

    2017-03-01

    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  9. [Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in intestinal disorders].

    Science.gov (United States)

    Gasztonyi, Beáta; Hunyady, Béla

    2004-10-24

    The authors report pharmacokinetics and indications of rifaximin and the results of clinical studies. Rifaximin has a large antibacterial spectrum with a good therapeutic effect on both gram positive and gram negative aerob and anaerob bacteria. Practically there is no absorption (< 1%) following oral administration with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase in absorption can be detected in intestinal damage caused by inflammatory bowel disease. The remarkable safety profile of rifaximin is due to its negligible quality of absorption. According to the clinical studies rifaximin could be an adequate therapeutic approach in all gastrointestinal diseases and interventions when antibacterial therapy is needed.

  10. Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Quattropani, Maria C; Calapai, Fabrizio; Gangemi, Sebastiano; Calapai, Gioacchino

    2014-06-01

    Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials. © 2014 John Wiley & Sons Ltd.

  11. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders

    Directory of Open Access Journals (Sweden)

    Jost WH

    2015-04-01

    Full Text Available Wolfgang H Jost,1 Reiner Benecke,2 Dieter Hauschke,3 Joseph Jankovic,4 Petr Kaňovský,5 Peter Roggenkämper,6 David M Simpson,7 Cynthia L Comella81Department of Neurology, University of Freiburg, Freiburg, Germany; 2Clinic and Policlinic for Neurology, University of Rostock, Rostock, Germany; 3Institute of Medical Biometry and Medical Informatics, University of Freiburg, Freiburg, Germany; 4Department of Neurology, Baylor College of Medicine, Houston, TX, USA; 5Department of Neurology, Palacky University Olomouc, Faculty of Medicine and Dentistry and University Hospital, Olomouc, Czech Republic; 6University Eye Clinic of Bonn, Bonn, Germany; 7Icahn School of Medicine at Mount Sinai, New York, NY, USA; 8Rush University Medical Center, Chicago, IL, USABackground: IncobotulinumtoxinA (Xeomin® is a purified botulinum neurotoxin type A formulation, free from complexing proteins, with proven efficacy and good tolerability for the treatment of neurological conditions such as blepharospasm, cervical dystonia (CD, and post-stroke spasticity of the upper limb. This article provides a comprehensive overview of incobotulinumtoxinA based on randomized controlled trials and prospective clinical studies.Summary: IncobotulinumtoxinA provides clinical efficacy in treating blepharospasm, CD, and upper-limb post-stroke spasticity based on randomized, double-blind, placebo-controlled trials with open-label extension periods (total study duration up to 89 weeks. Adverse events were generally mild or moderate. The most frequent adverse events, probably related to the injections, included eyelid ptosis and dry eye in the treatment of blepharospasm, dysphagia, neck pain, and muscular weakness in patients with CD, and injection site pain and muscular weakness when used for treating spasticity. In blepharospasm and CD, incobotulinumtoxinA was investigated in clinical trials permitting flexible intertreatment intervals based on the individual patient’s clinical need

  12. Thuja occidentalis (Arbor vitae): A Review of its Pharmaceutical, Pharmacological and Clinical Properties

    OpenAIRE

    Naser, Belal; Bodinet, Cornelia; Tegtmeier, Martin; Lindequist, Ulrike

    2005-01-01

    Arbor vitae (Thuja occidentalis L.) is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especial...

  13. Thuja occidentalis (Arbor vitae: A Review of its Pharmaceutical, Pharmacological and Clinical Properties

    Directory of Open Access Journals (Sweden)

    Belal Naser

    2005-01-01

    Full Text Available Arbor vitae (Thuja occidentalis L. is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especially the different contents of essential oil (Thujone in relation to different extraction procedures of this medicinal plant. Thuja's antiviral action and immunopharmacological potential, such as stimulatory and co-stimulatory effects on cytokine and antibody production and activation of macrophages and other immunocompetent cells, have been evaluated in numerous in vitro and in vivo investigations. Although no controlled trials have been conducted on Thuja occ alone, many clinical studies have been performed with a herbal medicinal product containing a special extract of Thuja occ and other immunostimulants, demonstrating its therapeutic efficacy and safety in respiratory tract infections.

  14. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  15. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Davis-Ajami ML

    2014-04-01

    Full Text Available Mary Lynn Davis-Ajami,1 Jun Wu,2 Katherine Downton,3 Emilie Ludeman,3 Virginia Noxon4 1Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA; 2South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA; 3Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA; 4Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L. This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. Keywords: biosimilar, chronic kidney disease, epoetin alfa, erythropoiesis, renal anemia, Retacrit®

  16. Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology.

    Science.gov (United States)

    Agúndez, José A G; Del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

  17. Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

    Science.gov (United States)

    Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe

    2016-09-22

    Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

  18. Educational Paper: Aspects of clinical pharmacology in children--pharmacovigilance and safety.

    Science.gov (United States)

    Choonara, Imti

    2013-05-01

    Adverse drug reactions (ADRs) are a significant problem in children, affecting one in ten children in hospital. Within the community, one in 500 children will experience an adverse drug reaction each year. Pharmacovigilance has been useful in detecting suspected ADRs. However, most ADRs are unreported and often not suspected. Education of health professionals in relation to drug toxicity improves the reporting rate of suspected ADRs. Clinical trials are useful to evaluate the efficacy of drugs. They are, however, not the best way of looking at ADRs where surveillance following the widespread use of a drug is more appropriate. Alongside work by the regulatory agencies, independent investigators have helped collate data. This information has been useful in developing guidelines to prevent further cases of drug toxicity. Greater awareness and understanding of drug toxicity in children should result in more rational prescribing.

  19. [Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia].

    Science.gov (United States)

    Kozlov, S P; Svetlov, V A; Luk'ianov, M V

    1998-01-01

    Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.

  20. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...

  1. CLINICAL AND PHARMACOLOGICAL APPROACHES TO OPTIMIZE THE DOSING REGIMEN OF ANTIBACTERIAL DRUGS IN PEDIATRICS

    Directory of Open Access Journals (Sweden)

    Natal’ya B. Lazareva

    2018-01-01

    Full Text Available The rational use of antibacterial drugs in children implies an adequate choice of the necessary medication, its dosing regimen, and the duration of treatment in order to achieve maximum efficacy and minimize toxic effects. The knowledge of pharmacokinetic and pharmacodynamic profiles of the antibacterial drug plays a crucial role for optimizing the dosing regimen. The strategy of individual choice of the dosing regimen, taking into account the principles of pharmacokinetics and pharmacodynamics, can be especially effective in patients with the expectedly changed parameters of pharmacokinetics and in infections caused by bacteria strains with low sensitivity to antibiotics. The review presents a contemporary view of pharmacokinetic and pharmacodynamic profiles of antibacterial drugs most commonly used in pediatrics and their relationship to the clinical efficacy of the administered therapy.

  2. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest : rationale and outline of the AmsteRdam Resuscitation Studies (ARREST) registry

    NARCIS (Netherlands)

    Blom, M T; van Hoeijen, D A; Bardai, A; Berdowski, J; Souverein, P C; De Bruin, M L; Koster, R W; de Boer, A; Tan, H L

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA.

  3. Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice.

    NARCIS (Netherlands)

    Snijders, G.F.; Ende, C.H.M. van den; Bemt, B.J.F van den; Riel, P.L.C.M. van; Hoogen, F.H.J. van den; Broeder, A. den

    2012-01-01

    OBJECTIVES: To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis (OA) in daily clinical practice. METHODS: In this observational cohort study, standardised conservative treatment was offered to patients

  4. Recent developments in the clinical pharmacology of rolapitant: subanalyses in specific populations

    Directory of Open Access Journals (Sweden)

    Rapoport BL

    2017-09-01

    Full Text Available Bernardo Leon Rapoport,1 Matti Aapro,2 Martin R Chasen,3 Karin Jordan,4 Rudolph M Navari,5 Ian Schnadig,6 Lee Schwartzberg7 1The Medical Oncology Centre of Rosebank, Johannesburg, South Africa; 2Breast Center, Genolier Cancer Center, Genolier, Switzerland; 3Palliative Care, William Osler Health Services, Brampton, ON, Canada; 4Department of Medicine V, University of Heidelberg, Heidelberg, Germany; 5Division of Hematology Oncology, University of Alabama School of Medicine, Birmingham, AL, USA; 6Compass Oncology, US Oncology Research, Tualatin, OR, USA; 7West Clinic, Memphis, TN, USA Abstract: Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs for control of chemotherapy-induced nausea and vomiting (CINV, in combination with serotonin type 3 receptor antagonists and corticosteroids. The NK-1 RA rolapitant, recently approved in oral formulation, has nanomolar affinity for the NK-1 receptor, as do the other commercially available NK-1 RAs, aprepitant and netupitant. Rolapitant is rapidly absorbed and has a long half-life in comparison to aprepitant and netupitant. All three NK-1 RAs undergo metabolism by cytochrome P450 (CYP 3A4, necessitating caution with the concomitant use of CYP3A4 inhibitors, but in contrast to aprepitant and netupitant, rolapitant does not inhibit or induce CYP3A4. However, rolapitant is a moderate inhibitor of CYP2D6, and concomitant use with CYP2D6 substrates with narrow therapeutic indices should be avoided. Aprepitant, netupitant, and rolapitant have all demonstrated efficacy in the control of delayed CINV in patients receiving moderately and highly emetogenic chemotherapy in randomized controlled trials, including over multiple cycles of chemotherapy. We reviewed recent post hoc analyses of clinical trial data demonstrating that rolapitant is efficacious in the control of CINV in patient populations with specific tumor types

  5. Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice.

    Science.gov (United States)

    Windsor, R; Oncken, C; Henningfield, J; Hartmann, K; Edwards, N

    2000-01-01

    Active and passive exposure to tobacco smoke are the most serious and preventable causes of poor maternal, fetal, and infant outcomes in the United States. Unfortunately, the majority of pregnant smokers do not quit smoking before or during pregnancy or after childbirth. We describe a standardized behavioral counseling model and discuss issues to consider in recommending the use of pharmacotherapy during pregnancy. Although the Food and Drug Administration no longer classifies nicotine replacement therapy (NRT) as contraindicated during pregnancy, precautions should be carefully considered for use in this population. This paper provides a synopsis of the risks of exposure to tobacco smoke during pregnancy and the postpartum; estimates the population at risk and the potential for increased cessation if effective health education methods during pregnancy were routinely provided; presents a meta-analysis of "best practice" patient education methods for pregnant smokers; and estimates the number of pregnant heavy smokers who might be eligible for NRT. We suggest five issues for the physician to consider before recommending NRT medications to pregnant patients who are heavy smokers. The judicious use of NRT medications may significantly reduce harm to the infants of heavy smokers. More evidence derived from large population-based research, however, is needed to provide guidance to the physician about NRT eligibility, dose, scheduling, and effectiveness in clinical practice.

  6. Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists.

    Science.gov (United States)

    Aghazadeh Tabrizi, Mojgan; Baraldi, Pier Giovanni; Baraldi, Stefania; Gessi, Stefania; Merighi, Stefania; Borea, Pier Andrea

    2017-07-01

    Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel. © 2016 Wiley Periodicals, Inc.

  7. Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

    Science.gov (United States)

    King, D J; Devaney, N

    1988-01-01

    The cardiovascular, anticholinergic and central effects of single doses of 30, 45 and 60 mg of sibutramine hydrochloride (BTS 54524), a new potential antidepressant, were compared with amitriptyline (50 mg) and placebo given at weekly intervals in a randomised design to six healthy male volunteers. Sibutramine was associated with increases in both supine heart rate and systolic blood pressure at 1, 2 and 6 h after 60 mg (P less than 0.05). Amitriptyline caused a significant 50-60% decrease in salivation compared with placebo at 2 and 6 h but there were no changes with sibutramine. No significant changes in pupil size were detected with either drug. Visual analogue rating scales (VARS) revealed significant drowsiness with amitriptyline but neither sedative nor stimulant effects with sibutramine. Impairments of simple auditory and visual reaction times, visual two-choice reaction time, finger tapping and trail making, measured using an automated test battery, occurred with amitriptyline compared with sibutramine. If sibutramine proves to be an effective antidepressant it should be devoid of anticholinergic or central depressant effects. Chronic dosage studies are indicated to evaluate the clinical significance of its cardiovascular effects. PMID:3207566

  8. Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.

    Science.gov (United States)

    Jorgensen, Sarah C J; Mercuro, Nicholas J; Davis, Susan L; Rybak, Michael J

    2018-03-31

    Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.

  9. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

    Science.gov (United States)

    Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

    2004-01-01

    Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

  10. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    extended release, efficacy, safety, resistance, clinical practice

  11. A HUMANIZED CLINICALLY CALIBRATED QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL FOR HYPOKINETIC MOTOR SYMPTOMS IN PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Hugo eGeerts

    2016-02-01

    Full Text Available The current treatment of Parkinson’s disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very succesfull, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor symptoms such as in cognitive and psychiatric domains. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a Quantitative Systems Pharmacology (QSP platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R2=0.71 with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations. When incorporating Parkinsonian (PD pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity from a dopamine depletion of 70% onwards. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R2=0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not

  12. Modafinil : A Review of its Pharmacology and Clinical Efficacy in the Management of Narcolepsy.

    Science.gov (United States)

    McClellan, K J; Spencer, C M

    1998-04-01

    Modafinil promotes wakefulness through an as yet unknown mechanism of action. It significantly increases daytime sleep latency and reduces excessive daytime sleepiness (EDS) compared with placebo in patients with narcolepsy. However, the drug does not suppress cataplexy. Although direct comparative data are lacking, modafinil offers advantages over amphetamines and methylphenidate in patients with narcolepsy because of its lack of rebound phenomena after treatment withdrawal and its low abuse potential. Clinical trials have shown modafinil to be well tolerated in patients with narcolepsy. Except for headache, which was reported with a significantly greater frequency in modafinil recipients, the tolerability profile of modafinil 200 to 400 mg/day was similar to that of placebo in patients treated for 9 weeks. Preliminary data suggest that the tolerability of modafinil is maintained long term (40 weeks). Thus, modafinil is effective in the treatment of EDS in patients with narcolepsy, although it is not effective against cataplexy. Preliminary findings indicate that, unlike other psychostimulants, the drug is unlikely to be abused and is not associated with withdrawal phenomena. Therefore, modafinil is likely to be an effective therapeutic option for the treatment of EDS in patients with narcolepsy. The mechanism of action of modafinil has not been clearly established. However, it may indirectly increase wakefulness, at least in part, through inhibition of cortical γ-aminobutyric acid (GABA) release via serotonergic mechanisms. Modafinil induces wakefulness and increases locomotor activity in a variety of animal species without causing stereotyped behaviour. In rhesus monkeys, the effects of oral modafinil were not associated with changes in blood pressure or heart rate. In contrast to dexamphetamine 20mg, single night-time doses of modafinil 100 or 200mg had no significant effects on objective sleep variables or sleep structure in young or elderly healthy

  13. Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review.

    Science.gov (United States)

    Lathers, Claire M; Smith, Cedric M

    2002-05-01

    The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from

  14. Clinical Trial of AC105 (Mg/PEG) for Treatment of Acute Spinal Cord Injury (SCI). Phase 2

    Science.gov (United States)

    2013-10-01

    glycol with a molecular weight of 3350 Daltons ( PEG 3350 ), is manufactured by Dow Chemical Company and complies with NF, FCC and EurPh requirements...Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) PRINCIPAL INVESTIGATOR: Andrew Blight, PhD RECIPIENT: Acorda Therapeutics...of AC105 (Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) 5b. GRANT NUMBER W81XWH-12-2 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  15. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  16. Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

    Science.gov (United States)

    Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

    2018-05-01

    CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  17. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

    Science.gov (United States)

    Sateia, Michael J.; Buysse, Daniel J.; Krystal, Andrew D.; Neubauer, David N.; Heald, Jonathan L.

    2017-01-01

    Introduction: The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. Methods: The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. Recommendations: The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of

  18. Anesthetic pharmacology

    National Research Council Canada - National Science Library

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

    2011-01-01

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

  19. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs

    Science.gov (United States)

    Nitsche, Michael A; Müller-Dahlhaus, Florian; Paulus, Walter; Ziemann, Ulf

    2012-01-01

    The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment. PMID:22869014

  20. AC Initiation System.

    Science.gov (United States)

    An ac initiation system is described which uses three ac transmission signals interlocked for safety by frequency, phase, and power discrimination...The ac initiation system is pre-armed by the application of two ac signals have the proper phases, and activates a load when an ac power signal of the proper frequency and power level is applied. (Author)

  1. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.

    Science.gov (United States)

    Sateia, Michael J; Buysse, Daniel J; Krystal, Andrew D; Neubauer, David N; Heald, Jonathan L

    2017-02-15

    The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading

  2. Lifestyle-oriented non-pharmacological treatments for fibromyalgia: a clinical overview and applications with home-based technologies

    Directory of Open Access Journals (Sweden)

    Friedberg F

    2012-10-01

    Full Text Available Fred Friedberg,1 David A Williams,2 William Collinge31Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, New York; 2Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 3Collinge and Associates, Kittery, Maine, USAAbstract: Fibromyalgia (FM is a persistent and disabling widespread pain condition often accompanied by chronic fatigue, cognitive problems, sleep disturbance, depression, anxiety, and headache. To date, the most thoroughly studied non-pharmacological approaches to managing FM are those with a focus on changing patient activities and beliefs that affect the illness. These interventions are intended to facilitate enduring improvement in pain and functional status. Lifestyle-oriented treatments include patient education, aerobic or other physical exercise, and cognitive-behavioral therapy (CBT. These interventions in FM can be delivered in medical or behavioral health care settings by trained professionals, through patient-oriented treatment manuals, or via remote-access technologies. Non-pharmacological treatments, in particular exercise and CBT, have yielded effect sizes and cost–benefit ratios comparable to medications. This paper describes lifestyle-oriented non-pharmacological treatments for FM and highlights selected literature reviews of these interventions. In addition, behavioral and practical issues are addressed that may affect these non-pharmacological treatments, including patient expectations, participant burden, and treatment availability. Recommendations are made to facilitate these interventions and potentially improve outcomes. In particular, the increasing availability of convenient home-based mobile technologies to deliver these non-pharmacological treatments is described.Keywords: cognitive-behavior therapy, exercise, education, mobile technology

  3. Clinical significance of combined detection of multiple serum antibodies (AsAb, EmAb, AcAb, AoAb, ToxAb) in infertile women

    International Nuclear Information System (INIS)

    Chen Jing; Jiang Li; Lu Ya

    2005-01-01

    Objective: To determine the clinical significance of combined detection of multiple serum antibodies in infertile women. Methods; Serum multiple antibodies were examined in 120 infertile women, including 88 failed to get pregnancy and 32 with repeated spontaneous abortion. The antibodies tested were: (1) anti-sperm antibody (AsAb) (2) endometrial antibody (EmAb) (3) anti-cardiophospholipid antibody (AcAb) (4) Anti-ovarian antibody (AoAb) and Toxoplasmosis antibody (ToxAb). Results: In 48 of the infertile women, none of the five antibodies were positive (40% of 120). The rest were: one antibody positive--38/120 or 31.6%; two antibodies positive--31/120 or 25.83%, three and four antibodies positive--4/120 or 3.33%. None of the women were positive with all five antibodies. Conclusion: Immune factor was the chief cause of infertility in women. (authors)

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

    Science.gov (United States)

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

    2018-05-01

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

  5. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

    Science.gov (United States)

    Wilt, Timothy J; MacDonald, Roderick; Brasure, Michelle; Olson, Carin M; Carlyle, Maureen; Fuchs, Erika; Khawaja, Imran S; Diem, Susan; Koffel, Erin; Ouellette, Jeannine; Butler, Mary; Kane, Robert L

    2016-07-19

    Pharmacologic interventions are often prescribed for insomnia disorder. To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. Eszopiclone, zolpidem, and

  6. Laboratory testing in the emergency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC and Academy of Emergency Medicine and Care (AcEMC consensus report

    Directory of Open Access Journals (Sweden)

    Giuseppe Lippi

    2017-04-01

    Full Text Available The mainstay of patient-oriented laboratory testing in emergency settings entails selecting number and type of tests according to valid criteria of appropriateness. Since the pattern of urgent tests requesting is variable across different institutions, we designed a joined survey between the Academy of Emergency Medicine and Care (AcEMC and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC for reaching tentative consensus about the most informative diagnostic tests in emergency settings. A survey, containing the most commonly performed urgent laboratory tests and the relative clinical indications, was disseminated to eight relevant members of AcEMC and eight relevant members of SIBioC. All contributors were asked to provide numerical scores for the different laboratory parameters, where 1 indicated strongly recommended, 2 recommended in specific circumstances, and 3 strongly discouraged. The mean results of the survey were presented as the mean of responders’ values, and the parameters were finally classified as strongly recommended (mean value, 1.0-1.5, somehow recommended (mean value, 1.5-2.0, discouraged (mean value, 2.0-2.5 and strongly discouraged (mean value, 2.5-3.0. The results of the survey allowed defining a hierarchy of priority, wherein 24 tests were strongly recommended. The use of 5 common tests was instead strongly discouraged. For 16 additional parameters in the list, the consensus ranged between somehow recommended and discouraged. We hope that results presented in this joint AcEMC-SIBioC consensus document may help harmonizing panel of tests and requesting patters in emergency setting, at least at a national level.

  7. Clinical significance of determination of serum hypersensitive C reactive protein (HS-CRP) levels in patients with acute coronary syndrome (ACS)

    International Nuclear Information System (INIS)

    Zhai Chunxi; Zhang Fengju; Wang Kejun

    2005-01-01

    Objective: To study the relationship between changes in serum HS-CRP levels and the status of atherosclerotic plaques in patients with ACS. Methods: Serum HS-CRP levels were measured in 35 patients with ACS at admission, 1 week and 1 month later as well as in 30 controls without recent infection. Results: HS-CRP levels in patients with ACS were significantly higher than those in the controls (P<0.01). The levels were highest at admission and fell gradually. Conclusion: HS-CRP could be a marker reflecting the status of atherosclerotic plaques in patients with ACS. (authors)

  8. [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.

  9. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression.

    Science.gov (United States)

    Lindemann, Lothar; Porter, Richard H; Scharf, Sebastian H; Kuennecke, Basil; Bruns, Andreas; von Kienlin, Markus; Harrison, Anthony C; Paehler, Axel; Funk, Christoph; Gloge, Andreas; Schneider, Manfred; Parrott, Neil J; Polonchuk, Liudmila; Niederhauser, Urs; Morairty, Stephen R; Kilduff, Thomas S; Vieira, Eric; Kolczewski, Sabine; Wichmann, Juergen; Hartung, Thomas; Honer, Michael; Borroni, Edilio; Moreau, Jean-Luc; Prinssen, Eric; Spooren, Will; Wettstein, Joseph G; Jaeschke, Georg

    2015-04-01

    Major depressive disorder (MDD) is a serious public health burden and a leading cause of disability. Its pharmacotherapy is currently limited to modulators of monoamine neurotransmitters and second-generation antipsychotics. Recently, glutamatergic approaches for the treatment of MDD have increasingly received attention, and preclinical research suggests that metabotropic glutamate receptor 5 (mGlu5) inhibitors have antidepressant-like properties. Basimglurant (2-chloro-4-[1-(4-fluoro-phenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]-pyridine) is a novel mGlu5 negative allosteric modulator currently in phase 2 clinical development for MDD and fragile X syndrome. Here, the comprehensive preclinical pharmacological profile of basimglurant is presented with a focus on its therapeutic potential for MDD and drug-like properties. Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. In microdialysis studies, basimglurant had no effect on monoamine transmitter levels in the frontal cortex or nucleus accumbens except for a moderate increase of accumbal dopamine, which is in line with its lack of pharmacological activity on monoamine reuptake transporters. These data taken together, basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy. Copyright © 2015 by The American Society for

  10. Guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: Consensus of a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

    Science.gov (United States)

    Reginster, Jean-Yves L; Arden, Nigel K; Haugen, Ida K; Rannou, Francois; Cavalier, Etienne; Bruyère, Olivier; Branco, Jaime; Chapurlat, Roland; Collaud Basset, Sabine; Al-Daghri, Nasser M; Dennison, Elaine M; Herrero-Beaumont, Gabriel; Laslop, Andrea; Leeb, Burkhard F; Maggi, Stefania; Mkinsi, Ouafa; Povzun, Anton S; Prieto-Alhambra, Daniel; Thomas, Thierry; Uebelhart, Daniel; Veronese, Nicola; Cooper, Cyrus

    2017-12-07

    To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis. While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Peltier ac calorimeter

    OpenAIRE

    Jung, D. H.; Moon, I. K.; Jeong, Y. H.

    2001-01-01

    A new ac calorimeter, utilizing the Peltier effect of a thermocouple junction as an ac power source, is described. This Peltier ac calorimeter allows to measure the absolute value of heat capacity of small solid samples with sub-milligrams of mass. The calorimeter can also be used as a dynamic one with a dynamic range of several decades at low frequencies.

  12. Low Offset AC Correlator.

    Science.gov (United States)

    This patent describes a low offset AC correlator avoids DC offset and low frequency noise by frequency operating the correlation signal so that low...noise, low level AC amplification can be substituted for DC amplification. Subsequently, the high level AC signal is demodulated to a DC level. (Author)

  13. A 1 year retrospective audit of quality indicators of clinical pharmacological advice for personalized linezolid dosing: one stone for two birds?

    Science.gov (United States)

    Pea, Federico; Cojutti, Piergiorgio; Dose, Lucia; Baraldo, Massimo

    2016-02-01

    This study explored the clinical and economic impact of clinical pharmacological advice (CPA) (based on therapeutic drug monitoring [TDM] results, and on patients' characteristics and co-medications) on personalized linezolid therapy in a tertiary care hospital. A 1 year retrospective analysis of quality indicators of CPA (clinicians' adherence rate to CPA, pre-post rate of linezolid trough concentrations within the desired range and cost balance analysis) was conducted. Five hundred and forty-four CPAs were provided to clinicians during 2014 for personalizing linezolid therapy in 168 patients. Clinicians' adherence to CPAs was very high (94.7%). The pre-post rate of linezolid Cmin distribution showed a favourable impact of CPA on patient care (pre-post ratio of Cmin within the desired range + 23.4%, pre, 51.2% vs. post, 74.6%). Overall, linezolid dosage was mainly reduced (56.9% of cases), whereas dose augmentation was needed only in a minority of cases (7.7%). Cost balance analysis showed that overall 1258 standard doses of linezolid (unitary dose 600 mg) were spared for treating 168 patients with a personalized dosage for a median duration of 11 days (range 3-128 days) with a cost saving of 60038.05 €. Active computerized advice elaborated by the clinical pharmacologist on the basis of TDM results and of patient's pathophysiological data and co-medications may be cost-effective for personalizing linezolid treatment. © 2015 The British Pharmacological Society.

  14. The pharmacology of regenerative medicine.

    Science.gov (United States)

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

    2013-07-01

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

  15. ACAC Converters for UPS

    Directory of Open Access Journals (Sweden)

    Rusalin Lucian R. Păun

    2008-05-01

    Full Text Available This paper propose a new control technique forsingle – phase ACAC converters used for a on-line UPSwith a good dynamic response, a reduced-partscomponents, a good output characteristic, a good powerfactorcorrection(PFC. This converter no needs anisolation transformer. A power factor correction rectifierand an inverter with the proposed control scheme has beendesigned and simulated using Caspoc2007, validating theconcept.

  16. Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove for new pharmacological interventions to enter clinical translation.

    Science.gov (United States)

    Sriram, Chandra Shekhar; Jangra, Ashok; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Bezbaruah, Babul Kumar

    2014-10-01

    The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1) functions at the center of cellular stress response and is mainly implied in DNA damage repair mechanism. Apart from its involvement in DNA damage repair, it does sway multiple vital cellular processes such as cell death pathways, cell aging, insulator function, chromatin modification, transcription and mitotic apparatus function. Since brain is the principal organ vulnerable to oxidative stress and inflammatory responses, upon stress encounters robust DNA damage can occur and intense PARP1 activation may result that will lead to various CNS diseases. In the context of soaring interest towards PARP1 as a therapeutic target for newer pharmacological interventions, here in the present review, we are attempting to give a silhouette of the role of PARP1 in the neurological diseases and the potential of its inhibitors to enter clinical translation, along with its structural and functional aspects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Vernakalant (RSD1235) in the management of atrial fibrillation: a review of pharmacological properties, clinical efficacy and safety

    DEFF Research Database (Denmark)

    Weeke, Peter; Andersson, Charlotte; Brendorp, Bente

    2008-01-01

    Vernakalant (RSD1235) is a novel antiarrhythmic agent for conversion of rapid onset atrial fibrillation (AF). It is an atria-selective multichannel ion blocker (blocks I(Kur), I(Na), I(Ca, L), I(to) and I(Kr)), with a small effect on ventricular repolarization. In clinical Phase II and III studie...... effect, with no reported cases of torsades de pointes in direct relation to vernakalant administration in Phase II and III studies. Overall, there are few reported serious adverse events.......Vernakalant (RSD1235) is a novel antiarrhythmic agent for conversion of rapid onset atrial fibrillation (AF). It is an atria-selective multichannel ion blocker (blocks I(Kur), I(Na), I(Ca, L), I(to) and I(Kr)), with a small effect on ventricular repolarization. In clinical Phase II and III studies...

  18. A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

    Science.gov (United States)

    Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

    2018-03-01

    To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

  19. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Marta Sacchetti

    2015-01-01

    Full Text Available Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP, a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients.

  20. 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.

  1. Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial.

    Science.gov (United States)

    Huffman, Mark D; Mohanan, Padinhare P; Devarajan, Raji; Baldridge, Abigail S; Kondal, Dimple; Zhao, Lihui; Ali, Mumtaj; Krishnan, Mangalath N; Natesan, Syam; Gopinath, Rajesh; Viswanathan, Sunitha; Stigi, Joseph; Joseph, Johny; Chozhakkat, Somanathan; Lloyd-Jones, Donald M; Prabhakaran, Dorairaj

    2018-02-13

    Wide heterogeneity exists in acute myocardial infarction treatment and outcomes in India. To evaluate the effect of a locally adapted quality improvement tool kit on clinical outcomes and process measures in Kerala, a southern Indian state. Cluster randomized, stepped-wedge clinical trial conducted between November 10, 2014, and November 9, 2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December 31, 2016. During 5 predefined steps over the study period, hospitals were randomly selected to move in a 1-way crossover from the control group to the intervention group. Consecutively presenting patients with acute myocardial infarction were offered participation. Hospitals provided either usual care (control group; n = 10 066 participants [step 0: n = 2915; step 1: n = 2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or care using a quality improvement tool kit (intervention group; n = 11 308 participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432; step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback, checklists, patient education materials, and linkage to emergency cardiovascular care and quality improvement training. The primary outcome was the composite of all-cause death, reinfarction, stroke, or major bleeding using standardized definitions at 30 days. Secondary outcomes included the primary outcome's individual components, 30-day cardiovascular death, medication use, and tobacco cessation counseling. Mixed-effects logistic regression models were used to account for clustering and temporal trends. Among 21 374 eligible randomized participants (mean age, 60.6 [SD, 12.0] years; n = 16 183 men [76%] ; n = 13 689 [64%] with ST-segment elevation myocardial infarction), 21 079 (99%) completed the trial. The primary composite outcome was observed in 5.3% of the intervention participants and 6.4% of the

  2. Vernakalant (RSD1235) in the management of atrial fibrillation: a review of pharmacological properties, clinical efficacy and safety

    DEFF Research Database (Denmark)

    Weeke, Peter; Andersson, Charlotte; Brendorp, Bente

    2008-01-01

    Vernakalant (RSD1235) is a novel antiarrhythmic agent for conversion of rapid onset atrial fibrillation (AF). It is an atria-selective multichannel ion blocker (blocks I(Kur), I(Na), I(Ca, L), I(to) and I(Kr)), with a small effect on ventricular repolarization. In clinical Phase II and III studie...... effect, with no reported cases of torsades de pointes in direct relation to vernakalant administration in Phase II and III studies. Overall, there are few reported serious adverse events....

  3. The antiprogesterone steroid RU 486: a short pharmacological and clinical review, with emphasis on the interruption of pregnancy.

    Science.gov (United States)

    Garfield, R E; Baulieu, E E

    1987-02-01

    In this review we have briefly outlined the clinical applications and mechanism of action of the progesterone antagonist RU 486. RU 486 has been successfully used in a variety of conditions to regulate the reproductive cycle and to control fertility in women. We suggest that the mechanism by which RU 486 acts during the cycle and early pregnancy is probably by affecting mainly the endometrium. During late pregnancy, the compound has significant effects on the myometrium including the induction of gap junctions between myometrium cells, which is required for muscle contractility during labour. The use of RU 486 has helped to demonstrate that progesterone is required for maintenance of the late stages of pregnancy in women.

  4. FLUIDIC AC AMPLIFIERS.

    Science.gov (United States)

    Several fluidic tuned AC Amplifiers were designed and tested. Interstage tuning and feedback designs are considered. Good results were obtained...corresponding Q’s as high as 12. Element designs and test results of one, two, and three stage amplifiers are presented. AC Modulated Carrier Systems

  5. Impact of amyloid-beta changes on cognitive outcomes in Alzheimer's disease: analysis of clinical trials using a quantitative systems pharmacology model.

    Science.gov (United States)

    Geerts, Hugo; Spiros, Athan; Roberts, Patrick

    2018-02-02

    Despite a tremendous amount of information on the role of amyloid in Alzheimer's disease (AD), almost all clinical trials testing this hypothesis have failed to generate clinically relevant cognitive effects. We present an advanced mechanism-based and biophysically realistic quantitative systems pharmacology computer model of an Alzheimer-type neuronal cortical network that has been calibrated with Alzheimer Disease Assessment Scale, cognitive subscale (ADAS-Cog) readouts from historical clinical trials and simulated the differential impact of amyloid-beta (Aβ40 and Aβ42) oligomers on glutamate and nicotinic neurotransmission. Preclinical data suggest a beneficial effect of shorter Aβ forms within a limited dose range. Such a beneficial effect of Aβ40 on glutamate neurotransmission in human patients is absolutely necessary to reproduce clinical data on the ADAS-Cog in minimal cognitive impairment (MCI) patients with and without amyloid load, the effect of APOE genotype effect on the slope of the cognitive trajectory over time in placebo AD patients and higher sensitivity to cholinergic manipulation with scopolamine associated with higher Aβ in MCI subjects. We further derive a relationship between units of Aβ load in our model and the standard uptake value ratio from amyloid imaging. When introducing the documented clinical pharmacodynamic effects on Aβ levels for various amyloid-related clinical interventions in patients with low Aβ baseline, the platform predicts an overall significant worsening for passive vaccination with solanezumab, beta-secretase inhibitor verubecestat and gamma-secretase inhibitor semagacestat. In contrast, all three interventions improved cognition in subjects with moderate to high baseline Aβ levels, with verubecestat anticipated to have the greatest effect (around ADAS-Cog value 1.5 points), solanezumab the lowest (0.8 ADAS-Cog value points) and semagacestat in between. This could explain the success of many amyloid

  6. AC power supply systems

    International Nuclear Information System (INIS)

    Law, H.

    1987-01-01

    An ac power supply system includes a rectifier fed by a normal ac supply, and an inverter connected to the rectifier by a dc link, the inverter being effective to invert the dc output of the receiver at a required frequency to provide an ac output. A dc backup power supply of lower voltage than the normal dc output of the rectifier is connected across the dc link such that the ac output of the rectifier is derived from the backup supply if the voltage of the output of the inverter falls below that of the backup supply. The dc backup power may be derived from a backup ac supply. Use in pumping coolant in nuclear reactor is envisaged. (author)

  7. PHARMACOLOGICAL IN VITRO MODELS IN PRE-CLINICAL DRUG TESTING - EXAMPLE OF hSERT TRANSFECTED HUMAN EMBRYONIC KIDNEY CELLS

    Directory of Open Access Journals (Sweden)

    Mihajlo Jakovljević

    2012-06-01

    Full Text Available Preclinical drug testing should be considered an important stage during examinations of its efficiency and safety in any likely indication observed. Purpose of the process is acquisition of substantial amount of particular drug-related data before approaching clinical trials in humans. Historical preclinical testing relied on available testing in microbe cultures and animal models. During recent decades laboratory techniques of human cell lines cultivation have been developed and improved. These provide unique possibility of drug acting mechanism testing in a simplified environment lacking basic homeostatic mechanisms. Some examples of these are measuring drug impact to biochemical transport, signaling or anabolic processes. Humane cell lines of embrional kidney 293 are an example of easy-to-grow and disseminate and quite endurable cell line. This methodological article notices some of the details of HEK293 cells cultivation and breading. We took transfection as an example of in vitro model creation for drug testing. Transfection refers to gene introduction into HEK293 cellular genome in order to achieve membrane expression of coded protein. In our case it would be human serotonin transporter. Article contains description of one particular methodological approach in measuring human serotonin transporter expression. The role and importance of serotonin pump in affective disorders genesis was already widely recognized. Aim of the paper was to emphasize feasibility of cell cultivation and its advantages in comparison with alternative traditional methods.

  8. Theoretical overview of clinical and pharmacological aspects of the use of etelcalcetide in diabetic patients undergoing hemodialysis

    Directory of Open Access Journals (Sweden)

    Ye J

    2018-04-01

    Full Text Available Jianzhen Ye,1 Guangrui Deng,1 Feng Gao2 1Department of Endocrinology, Huangzhou District People’s Hospital, Huanggang, People’s Republic of China; 2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: Etelcalcetide is the first intravenous calcimimetic agent authorized for the treatment of secondary hyperparathyroidism (sHPT in patients undergoing hemodialysis in Europe, the US, and Japan. The relationship between sHPT and diabetes resides on complex, bidirectional effects and largely unknown homeostatic mechanisms. Although 30% or more patients with end-stage renal disease are diabetics and about the same percentage of those patients suffer from sHPT associated with hemodialysis, no data on the specificities of the use of etelcalcetide in such patients are available yet. Regarding pharmacokinetic interactions, etelcalcetide may compete with oral hypoglycemics recommended for use in patients undergoing hemodialysis and insulins detemir and degludec, causing unexpected hypocalcemia or hypoglycemia. More importantly, hypocalcemia, a common side effect of etelcalcetide, may cause decompensation of preexisting cardiac insufficiency in diabetic patients or worsen dialysis-related hypotension and lead to hypotension-related cardiac events, such as myocardial ischemia. In diabetic patients, hypocalcemia may lead to dangerous ventricular arrhythmias, as both insulin-related hypoglycemia and hemodialysis prolong QT interval. Patients with diabetes, therefore, should be strictly monitored for hypocalcemia and associated effects. Due to an altered parathormone activity in this patient group, plasma calcium should be the preferred indicator of etelcalcetide effects. Until more clinical experience with etelcalcetide is available, the clinicians should be cautious when using this calcimimetic in patients with diabetes. Keywords: glucose intolerance

  9. ACS Zero Point Verification

    Science.gov (United States)

    Dolphin, Andrew

    2005-07-01

    The uncertainties in the photometric zero points create a fundamental limit to the accuracy of photometry. The current state of the ACS calibration is surprisingly poor, with zero point uncertainties of 0.03 magnitudes. The reason for this is that the ACS calibrations are based primarily on semi-emprical synthetic zero points and observations of fields too crowded for accurate ground-based photometry. I propose to remedy this problem by obtaining ACS images of the omega Cen standard field with all nine broadband ACS/WFC filters. This will permit the direct determination of the ACS zero points by comparison with excellent ground-based photometry, and should reduce their uncertainties to less than 0.01 magnitudes. A second benefit is that it will facilitate the comparison of the WFPC2 and ACS photometric systems, which will be important as WFPC2 is phased out and ACS becomes HST's primary imager. Finally, three of the filters will be repeated from my Cycle 12 observations, allowing for a measurement of any change in sensitivity.

  10. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest: rationale and outline of the AmsteRdam Resuscitation Studies (ARREST) registry

    Science.gov (United States)

    Blom, M T; van Hoeijen, D A; Bardai, A; Berdowski, J; Souverein, P C; De Bruin, M L; Koster, R W; de Boer, A; Tan, H L

    2014-01-01

    Introduction Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA. Methods and analysis We set up a large-scale prospective community-based registry (AmsteRdam Resuscitation Studies, ARREST) in which we prospectively include all resuscitation attempts from OHCA in a large study region in the Netherlands in collaboration with Emergency Medical Services. Of all OHCA victims since June 2005, we prospectively collect medical history (through hospital and general practitioner), and current and previous medication use (through community pharmacy). In addition, we include DNA samples from OHCA victims with documented ventricular tachycardia/fibrillation during the resuscitation attempt since July 2007. Various study designs are employed to analyse the data of the ARREST registry, including case–control, cohort, case only and case-cross over designs. Ethics and dissemination We describe the rationale, outline and potential results of the ARREST registry. The design allows for a stable and reliable collection of multiple determinants of OHCA, while assuring that the patient, lay-caregiver or medical professional is not hindered in any way. Such comprehensive data collection is required to unravel the complex basis of OHCA. Results will be published in peer-reviewed journals and presented at relevant scientific symposia. PMID:25332818

  11. AcMNPV

    African Journals Online (AJOL)

    USER

    2010-08-16

    Aug 16, 2010 ... biosynthesis pathway and plays an important role in insect growth and .... Construction and propagation of recombined AcMNPV. The recombined ... infected by virus increased with incubation time (Figure. 3). The growth of ...

  12. AC BREAKDOWN IN GASES

    Science.gov (United States)

    electron- emission (multipactor) region, and (3) the low-frequency region. The breakdown mechanism in each of these regions is explained. An extensive bibliography on AC breakdown in gases is included.

  13. THERMIONIC AC GENERATION

    Science.gov (United States)

    is shown that the maximum ac efficiency is equal to approximately 70% of the corresponding dc value. An illustrative example, including a proposed design for a rather unconventional transformer, is appended. (Author)

  14. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

  15. Sequential application of non-pharmacological interventions reduces the severity of labour pain, delays use of pharmacological analgesia, and improves some obstetric outcomes: a randomised trial

    Directory of Open Access Journals (Sweden)

    Rubneide Barreto Silva Gallo

    2018-01-01

    Trial registration: NCT01389128. [Gallo RBS, Santana LS, Marcolin AC, Duarte G, Quintana SM (2018 Sequential application of non-pharmacological interventions reduces the severity of labour pain, delays use of pharmacological analgesia, and improves some obstetric outcomes: a randomised trial. Journal of Physiotherapy 64: 33–40

  16. Mass of AC Andromedae

    International Nuclear Information System (INIS)

    King, D.S.; Cox, A.N.; Hodson, S.W.

    1975-01-01

    Calculations indicate that AC Andromedae is population I rather than population II. A mass and radius for this star are calculated using a new set of opacities for the Kippenhahn Ia mixture. It is concluded that the mass is too high for an ordinary RR Lyrae star. (BJG)

  17. AC/RF Superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Ciovati, G [Jefferson Lab (United States)

    2014-07-01

    This contribution provides a brief introduction to AC/RF superconductivity, with an emphasis on application to accelerators. The topics covered include the surface impedance of normal conductors and superconductors, the residual resistance, the field dependence of the surface resistance, and the superheating field.

  18. AC/RF Superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Ciovati, Gianluigi [JLAB

    2015-02-01

    This contribution provides a brief introduction to AC/RF superconductivity, with an emphasis on application to accelerators. The topics covered include the surface impedance of normal conductors and superconductors, the residual resistance, the field dependence of the surface resistance, and the superheating field.

  19. Efficacy and safety of a novel pharmacological stress test agent-higenamine in radionuclide myocardial perfusion imaging: phase Ⅱ clinical trial

    International Nuclear Information System (INIS)

    Du Yanrong; Li Fang; Wang Qian; Li Dianfu; Long Mingqing; Liu Yimin; Li Bilu

    2014-01-01

    of diastolic blood pressure. Either HG or Ad induced significantly increased HR during administration and 5 min after administration. The clinical laboratory profile (hematology,serum chemistry, and urinalysis) was either normal or with no significant change. A total of 176 side effects (e.g, dyspnea, short breath, palpitation, dizziness,headache) were found related to HG (69.2%, 83/120) and Ad (77.5%, 93/120) administration (χ 2 =2.1307, P>0.05), which were mostly mild and transient. Conclusion: HG is a safe and effective pharmacological stress test agent as compared to adenosine for the detection of CAD with SPECT perfusion imaging. (authors)

  20. Traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis: A review.

    Science.gov (United States)

    Gao, Shi-Man; Liu, Jiu-Shi; Wang, Min; Cao, Ting-Ting; Qi, Yao-Dong; Zhang, Ben-Gang; Sun, Xiao-Bo; Liu, Hai-Tao; Xiao, Pei-Gen

    2018-06-12

    Species of the genus Codonopsis are perennial herbs mainly distributed throughout East, Southeast and Central Asia. As recorded, they have been used as traditional Chinese medicines since the Qing Dynasty, where they were claimed for strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. Some species are also used as food materials in southern China and Southeast Asia, such as tea, wine, soup, plaster, and porridge. The review aims to assess the ethnopharmacological uses, explicit the material basis and pharmacological action, promote the safety of medical use, and suggest the future research potentials of Codonopsis. Information on the studies of Codonopsis was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, Researchgate, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters Dissertation. Plant taxonomy was confirmed to the database "The Plant List" (www.theplantlist.org). Codonopsis has been used for medicinal purposes all around the world. Some species are also used as food materials in southern China and Southeast Asia. The chemical constituents of Codonopsis mainly are polyacetylenes, polyenes, flavonoids, lignans, alkaloids, coumarins, terpenoids, steroids, organic acids, saccharides, and so on. Extract of Codonopsis exhibit extensive pharmacological activities, including immune function regulation, hematopoiesis improvement, cardiovascular protection, neuroprotection, gastrointestinal function regulation, endocrine function regulation, cytotoxic and antibacterial effects, anti-aging and anti-oxidation, etc. Almost no obvious toxicity or side effect are observed and recorded for Codonopsis. The traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis are

  1. BPS Pharmacology 2014 - Drug Discovery Pathways symposium Report

    OpenAIRE

    Marsh, Andrew

    2015-01-01

    Report on BPS Pharmacology 2014, BPS Industry Committe and Learned Societies Drug Discovery Pathways Group symposium: "Realizing the potential of new approaches to target identification and validation" by Dr Andrew Marsh Associate Professor Department of Chemistry University of Warwick go.warwick.ac.uk/marshgroup Twitter @marshgroup

  2. 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...

  3. Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac transposition

    International Nuclear Information System (INIS)

    Jarvis, P.; Belzile, F.; Page, T.; Dean, C.

    1997-01-01

    The maize transposable element Ac is highly active in the heterologous hosts tobacco and tomato, but shows very much reduced levels of activity in Arabidopsis. A mutagenesis experiment was undertaken with the aim of identifying Arabidopsis host factors responsible for the observed low levels of Ac activity. Seed from a line carrying a single copy of the Ac element inserted into the streptomycin phosphotransferase (SPT) reporter fusion, and which displayed typically low levels of Ac activity, were mutagenized using gamma rays. Nineteen mutants displaying high levels of somatic Ac activity, as judged by their highly variegated phenotypes, were isolated after screening the M2 generation on streptomycin-containing medium. The mutations fall into two complementation groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a Mendelian fashion. The iae1 mutation is recessive and the iae2 mutation is semi-dominant. The iae1 and iae2 mutants show 550- and 70-fold increases, respectively, in the average number of Ac excision sectors per cotyledon. The IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome 3. A molecular study of Ac activity in the iae1 mutant confirmed the very high levels of Ac excision predicted using the phenotypic assay, but revealed only low levels of Ac re-insertion. Analyses of germinal transposition in the iae1 mutant demonstrated an average germinal excision frequency of 3% and a frequency of independent Ac re-insertions following germinal excision of 22%. The iae mutants represents a possible means of improving the efficiency of Ac/Ds transposon tagging systems in Arabidopsis, and will enable the dissection of host involvement in Ac transposition and the mechanisms employed for controlling transposable element activity

  4. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

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

    2015-01-01

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

  5. Superconducting ac cable

    Science.gov (United States)

    Schmidt, F.

    1980-11-01

    The components of a superconducting 110 kV ac cable for power ratings or = 2000 MVA were developed. The cable design is of the semiflexible type, with a rigid cryogenic envelope containing a flexible hollow coaxial cable core. The cable core consists of spirally wound Nb-A1 composite wires electrically insulated by high pressure polyethylene tape wrappings. A 35 m long single phase test cable with full load terminals rated at 110 kV and 10 kA was constructed and successfully tested. The results obtained prove the technical feasibility and capability of this cable design.

  6. ac superconducting articles

    International Nuclear Information System (INIS)

    Meyerhoff, R.W.

    1977-01-01

    A noval ac superconducting cable is described. It consists of a composite structure having a superconducting surface along with a high thermally conductive material wherein the superconducting surface has the desired physical properties, geometrical shape and surface finish produced by the steps of depositing a superconducting layer upon a substrate having a predetermined surface finish and shape which conforms to that of the desired superconducting article, depositing a supporting layer of material on the superconducting layer and removing the substrate, the surface of the superconductor being a replica of the substrate surface

  7. Superconducting ac cable

    International Nuclear Information System (INIS)

    Schmidt, F.

    1980-01-01

    The components of a superconducting 110 kV ac cable for power ratings >= 2000 MVA have been developed. The cable design especially considered was of the semiflexible type, with a rigid cryogenic envelope and flexible hollow coaxial cable cores pulled into the former. The cable core consists of spirally wound Nb-Al composite wires and a HDPE-tape wrapped electrical insulation. A 35 m long single phase test cable with full load terminations for 110 kV and 10 kA was constructed and successfully tested. The results obtained prove the technical feasibility and capability of our cable design. (orig.) [de

  8. International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

    Science.gov (United States)

    Kaczmarek, Leonard K; Aldrich, Richard W; Chandy, K George; Grissmer, Stephan; Wei, Aguan D; Wulff, Heike

    2017-01-01

    A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium. This article describes the molecular relationships between these channels and provides an introduction to their functional properties. It also introduces a new nomenclature that differentiates between calcium- and sodium-activated potassium channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Perinatal pharmacology: applications for neonatal neurology.

    Science.gov (United States)

    Smits, Anne; Allegaert, Karel

    2011-11-01

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

  10. Biological and Pharmacological properties

    Indian Academy of Sciences (India)

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

  11. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

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

  12. The pharmacology of gynaecology.

    Science.gov (United States)

    Tothill, A

    1980-09-01

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

  13. ACS Postflash Characterization

    Science.gov (United States)

    Smith, Linda

    2011-10-01

    This program will evaluate the in-flight performance of the ACS/WFC post-flash lamp. A series of observations of Omega Cen will be taken using short and long exposures. The short exposures will be post-flashed using pre-determined exposure times to produce backgrounds from 0 to 125 e-. The data will be used to {1} make an empirical study of the effectiveness in preserving counts for faint stars on various post-flash backgrounds; {2} validate that our current mechanisms for formula-based and pixel-based corrections provide good fixes for whatever CTE remains; and {3} probe a fine enough range of backgrounds that users will be able to pick the level that optimizes their science, which will be a straightforward compromise between the noise added and the signal preserved.

  14. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

    Science.gov (United States)

    Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

    2016-08-01

    Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

  15. Iomazenil: pharmacological and animal data

    International Nuclear Information System (INIS)

    Beer, H.F.; Blaeuenstein, P.A.; Hasler, P.H.; Schubiger, P.A.; Hunkeler, W.; Bibettu, E.P.; Pieri, L.; Grayson Richards, J.

    1990-01-01

    The flumazenil analogue Ro 16-0154 (Iomazenil), a benzodiazepine partial inverse agonist, has been labelled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in human brain. The purified 123 I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacological properties were comparable to those of flumazenil with the exception of the antagonism of diazepam versus pentylenetetrazol. Biodistribution in rats (1 h p.i.) resulted in a high brain to blood ratio of 16. Clinical studies revealed images of the bezodiazepine receptor density in the brain. (author) 9 figs., 3 tabs., 27 refs

  16. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  17. Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

    Science.gov (United States)

    Wang, Ting; Guo, Rixin; Zhou, Guohong; Zhou, Xidan; Kou, Zhenzhen; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

    2016-07-21

    Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng. Copyright © 2016

  18. Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies.

    Science.gov (United States)

    Zeilinger, Katrin; Schreiter, Thomas; Darnell, Malin; Söderdahl, Therese; Lübberstedt, Marc; Dillner, Birgitta; Knobeloch, Daniel; Nüssler, Andreas K; Gerlach, Jörg C; Andersson, Tommy B

    2011-05-01

    Within the scope of developing an in vitro culture model for pharmacological research on human liver functions, a three-dimensional multicompartment hollow fiber bioreactor proven to function as a clinical extracorporeal liver support system was scaled down in two steps from 800 mL to 8 mL and 2 mL bioreactors. Primary human liver cells cultured over 14 days in 800, 8, or 2 mL bioreactors exhibited comparable time-course profiles for most of the metabolic parameters in the different bioreactor size variants. Major drug-metabolizing cytochrome P450 activities analyzed in the 2 mL bioreactor were preserved over up to 23 days. Immunohistochemical studies revealed tissue-like structures of parenchymal and nonparenchymal cells in the miniaturized bioreactor, indicating physiological reorganization of the cells. Moreover, the canalicular transporters multidrug-resistance-associated protein 2, multidrug-resistance protein 1 (P-glycoprotein), and breast cancer resistance protein showed a similar distribution pattern to that found in human liver tissue. In conclusion, the down-scaled multicompartment hollow fiber technology allows stable maintenance of primary human liver cells and provides an innovative tool for pharmacological and kinetic studies of hepatic functions with small cell numbers.

  19. Superconductive AC current limiter

    International Nuclear Information System (INIS)

    Bekhaled, M.

    1987-01-01

    This patent describes an AC current limiter for a power transport line including a power supply circuit and feeding a load circuit via an overload circuit-breaker member. The limiter comprises a transformer having a primary winding connected in series between the power supply circuit and the load circuit and at least one secondary winding of superconductor material contained in a cryogenic enclosure and short-circuited on itself. The leakage reactance of the transformer as seen from the primary winding is low, and the resistance of the at least one secondary winding when in the non-superconducting state and as seen from the primary is much greater than the nominal impedance of the transformer. The improvement whereby the at least one secondary winding of the transformer comprises an active winding in association with a set of auxiliary windings. The set of auxiliary windings is constituted by an even number of series-connected auxiliary windings wound in opposite directions, with the total number of turns in one direction being equal to the total number of turns in the opposite direction, and with the thermal capacity of the secondary winding as a whole being sufficiently high to limit the expansion thereof to a value which remains small during the time it takes the circuit-breaking member to operate

  20. ACS Photometric Zero Point Verification

    Science.gov (United States)

    Dolphin, Andrew

    2003-07-01

    The uncertainties in the photometric zero points create a fundamental limit to the accuracy of photometry. The current state of the ACS calibration is surprisingly poor, with zero point uncertainties of 0.03 magnitudes in the Johnson filters. The reason for this is that ACS observations of excellent ground-based standard fields, such as the omega Cen field used for WFPC2 calibrations, have not been obtained. Instead, the ACS photometric calibrations are based primarily on semi-emprical synthetic zero points and observations of fields too crowded for accurate ground-based photometry. I propose to remedy this problem by obtaining ACS broadband images of the omega Cen standard field with both the WFC and HRC. This will permit the direct determination of the ACS transformations, and is expected to double the accuracy to which the ACS zero points are known. A second benefit is that it will facilitate the comparison of the WFPC2 and ACS photometric systems, which will be important as WFPC2 is phased out and ACS becomes HST's primary imager.

  1. Introduction to AC machine design

    CERN Document Server

    Lipo, Thomas A

    2018-01-01

    AC electrical machine design is a key skill set for developing competitive electric motors and generators for applications in industry, aerospace, and defense. This book presents a thorough treatment of AC machine design, starting from basic electromagnetic principles and continuing through the various design aspects of an induction machine. Introduction to AC Machine Design includes one chapter each on the design of permanent magnet machines, synchronous machines, and thermal design. It also offers a basic treatment of the use of finite elements to compute the magnetic field within a machine without interfering with the initial comprehension of the core subject matter. Based on the author's notes, as well as after years of classroom instruction, Introduction to AC Machine Design: * Brings to light more advanced principles of machine design--not just the basic principles of AC and DC machine behavior * Introduces electrical machine design to neophytes while also being a resource for experienced designers * ...

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

    Science.gov (United States)

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

    2017-01-01

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

  3. 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...

  4. Aislamiento acústico

    Directory of Open Access Journals (Sweden)

    Tobío, J. M.

    1970-07-01

    Full Text Available This is a very specific subject in the field of architectural acoustics, namely, insulation'. Emphasis is placed on the theoretical foundations of this phenomenon, and the most simple formula are developed to calculate easily the transmission losses of a material or the constructional insulating arrangements. The practical aspect of insulation can be considered by means of several graphs and charts, without the use of mathematics, and utilising common materials, that will not substantially increase the cost of the project. Finally this papers offers a critical discussion of building codes, and their reference to the acoustical insulation of dwellings, and data is included on the new regulations of the Madrid Municipality.Se trata un tema muy concreto de la Acústica Arquitectónica, el aislamiento, haciendo hincapié en los fundamentos teóricos del fenómeno y estableciendo las fórmulas más sencillas que permiten calcular fácilmente las pérdidas de transmisión de un material o disposición constructiva aislante. Varias gráficas y abacos permiten abordar, sin ningún tratamiento matemático, el problema práctico del aislamiento, aprovechando los materiales comunes y sin ocasionar gastos que graven sustancialmente el importe del proyecto. Por último, se hace un estudio crítico de las normas y su incidencia en los problemas del aislamiento de viviendas, incluyendo datos referentes a la nueva Ordenanza del Ayuntamiento de Madrid.

  5. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

    Science.gov (United States)

    Derfuss, Tobias; Curtin, François; Guebelin, Claudia; Bridel, Claire; Rasenack, Maria; Matthey, Alain; Du Pasquier, Renaud; Schluep, Myriam; Desmeules, Jules; Lang, Alois B; Perron, Hervé; Faucard, Raphael; Porchet, Hervé; Hartung, Hans-Peter; Kappos, Ludwig; Lalive, Patrice H

    2015-06-01

    GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period. © The Author(s) 2014.

  7. Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment

    NARCIS (Netherlands)

    Molendijk, M.L.; Bus, B.A.A.; Spinhoven, P.; Penninx, B.W.J.H.; Kenis, G.; Prickaerts, J.; Voshaar, R.C.O.; Elzinga, B.M.

    2011-01-01

    Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression,

  8. [Pharmacological therapy of obesity].

    Science.gov (United States)

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

    2008-04-01

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

  9. 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)

  10. Traumatic brain injury pharmacological treatment: recommendations

    Directory of Open Access Journals (Sweden)

    Renato Anghinah

    Full Text Available ABSTRACT This article presents the recommendations on the pharmacological treatment employed in traumatic brain injury (TBI at the outpatient clinic of the Cognitive Rehabilitation after TBI Service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. A systematic assessment of the consensus reached in other countries, and of articles on TBI available in the PUBMED and LILACS medical databases, was carried out. We offer recommendations of pharmacological treatments in patients after TBI with different symptoms.

  11. Pharmacological management of panic disorder

    Directory of Open Access Journals (Sweden)

    Carlo Marchesi

    2008-03-01

    Full Text Available Carlo MarchesiPsychiatric Section, Department of Neuroscience, University of Parma, Parma, ItalyAbstract: Panic disorder (PD is a disabling condition which appears in late adolescence or early adulthood and affects more frequently women than men. PD is frequently characterized by recurrences and sometimes by a chronic course and, therefore, most patients require longterm treatments to achieve remission, to prevent relapse and to reduce the risks associated with comorbidity. Pharmacotherapy is one of the most effective treatments of PD. In this paper, the pharmacological management of PD is reviewed. Many questions about this effective treatment need to be answered by the clinician and discussed with the patients to improve her/his collaboration to the treatment plan: which is the drug of choice; when does the drug become active; which is the effective dose; how to manage the side effects; how to manage nonresponse; and how long does the treatment last. Moreover, the clinical use of medication in women during pregnancy and breastfeeding or in children and adolescents was reviewed and its risk-benefit balance discussed.Keywords: panic disorder, pharmacological treatment, treatment guidelines

  12. Medicinal uses, phytochemistry and pharmacology of the genus Uncaria.

    Science.gov (United States)

    Zhang, Qian; Zhao, Jiao Jiao; Xu, Jian; Feng, Feng; Qu, Wei

    2015-09-15

    The genus Uncaria belongs to the family Rubiaceae, which mainly distributed in tropical regions, such as Southeast Asia, Africa and Southeast America. Their leaves and hooks have long been thought to have healing powers and are already being tested as a treatment for asthma, cancer, cirrhosis, diabetes, hypertension, stroke and rheumatism. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of the genus Uncaria to support for further therapeutic potential of this genus. To better understanding this genus, information on the stereo-chemistry and structure-activity relationships in indole alkaloids is also represented. The literature study of this review is based on various databases search (SCIFinder, Science Direct, CNKI, Wiley online library, Spring Link, Web of Science, PubMed, Wanfang Data, Medalink, Google scholar, ACS, Tropicos, Council of Heads of Australasian Herbaria, The New York Botanical Garden, African Plants Database at Genera Botanical Garden, The Plant List and SEINet) and library search for Biological Abstract and some local books on ethnopharmacology. 19 species of the genus Uncaria are found to be important folk medicines in China, Malaysia, Phillippines, Africa and Southeast America, etc, and have been served for the treatment of asthma, rheumatism, hyperpyrexia, hypertension and headaches, etc. More than 200 compounds have been isolated from Uncaria, including indole alkaloids, triterpenes, flavonoids, phenols, phenylpropanoids, etc. As characteristic constituents, indole alkaloids have been considered as main efficacy component for hypertension, epilepsy, depressant, Parkinson's disease and Alzheimer's disease. In addition, pharmacokinetic and metabolism investigation reveal that the indole alkaloids are likely to be absorbed, metabolized and excreted at early time points. Moreover, the specific inhibition of CYP isozymes can regulate their hydroxylation metabolites

  13. Pharmacological effects of biotin.

    Science.gov (United States)

    Fernandez-Mejia, Cristina

    2005-07-01

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

  14. Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

    Science.gov (United States)

    Zheng, Jolene; Vasselli, Joseph R; King, Jason F; King, Michael L; We, Wenqian; Fitzpatrick, Zachary; Johnson, William D; Finley, John W; Martin, Roy J; Keenan, Michael J; Enright, Frederic M; Greenway, Frank L

    The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 μg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 μg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

  15. Arformoterol Tartrate: A Review of Pharmacology, Analysis and ...

    African Journals Online (AJOL)

    Erah

    suggest the potentially enhanced efficacy of this drug in the treatment of COPD including ... pharmacology, pharmacokinetics, clinical studies, analytical techniques, drug-drug interactions, ..... accordance with the United States Food and. Drug ...

  16. Integrated quantitative pharmacology for treatment optimization in oncology

    NARCIS (Netherlands)

    Hasselt, J.G.C. van

    2014-01-01

    This thesis describes the development and application of quantitative pharmacological models in oncology for treatment optimization and for the design and analysis of clinical trials with respect to pharmacokinetics, toxicity, efficacy and cost-effectiveness. A recurring theme throughout this

  17. 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.

  18. Atomoxetine in patients with ADHD: A clinical and pharmacological review of the onset, trajectory, duration of response and implications for patients.

    Science.gov (United States)

    Clemow, David B; Bushe, Chris J

    2015-12-01

    This article reviews data providing new insight into the trajectory of response and maintenance of response of atomoxetine in the treatment of child and adult attention-deficit hyperactivity disorder (ADHD). This nonsystematic review includes: onset of action and duration of effect, response rate, effect size, time to optimal response and norepinephrine transporter blockade biomarker data. Atomoxetine can have an onset of action within 1-2 weeks of starting treatment, but there is an incrementally increasing response for up to 24 weeks or longer. Responder rates and effect sizes are similar to methylphenidate. Upon treatment discontinuation, relapse rates are lower than expected. In adults, 50% maintain their response for at least 6 months after stopping atomoxetine, following 6 months of treatment. Single-dose atomoxetine can provide 24-hour efficacy, despite a 5-hour plasma half-life. Hypotheses can be generated relating to neuroadaptive changes, to explain these findings. Atomoxetine has a trajectory of response that is incremental over a long period of time, with a greater than expected maintenance of response. This has implications for physician atomoxetine dosing and efficacy assessment, patient education and outcomes, and for clinical trial design and assessment of comparative efficacy with stimulant medications. © The Author(s) 2015.

  19. Hopping models and ac universality

    DEFF Research Database (Denmark)

    Dyre, Jeppe; Schrøder, Thomas

    2002-01-01

    Some general relations for hopping models are established. We proceed to discuss the universality of the ac conductivity which arises in the extreme disorder limit of the random barrier model. It is shown that the relevant dimension entering into the diffusion cluster approximation (DCA) is the h......Some general relations for hopping models are established. We proceed to discuss the universality of the ac conductivity which arises in the extreme disorder limit of the random barrier model. It is shown that the relevant dimension entering into the diffusion cluster approximation (DCA......) is the harmonic (fracton) dimension of the diffusion cluster. The temperature scaling of the dimensionless frequency entering into the DCA is discussed. Finally, some open problems regarding ac universality are listed....

  20. Syzygium Cordatum Hochst. ex Krauss: An Overview of Its Ethnobotany, Phytochemistry and Pharmacological Properties

    Directory of Open Access Journals (Sweden)

    Alfred Maroyi

    2018-05-01

    Full Text Available Syzygium cordatum is a valuable medicinal plant in the materia medica of east and southern Africa. The aim of this study was to review the botany, medicinal uses, phytochemistry and ethnopharmacological properties of S. cordatum. Relevant literature search was carried out using internet sources such as ACS, Web of Science, Wiley, SpringerLink, Scopus, Mendeley, Google Scholar, Pubmed, SciFinder, BioMed Central, Science Direct and Elsevier. Other literature sources were conference papers, book chapters, books, theses and websites. The leaves, roots, bark and fruits of S. cordatum are used as ethnomedicines against 24 human diseases such as gastro-intestinal disorders, burns, sores, wounds, colds, cough, respiratory complaints, sexually transmitted infections (STIs, tuberculosis, fever and malaria. Several phytochemical compounds including alkaloids, anthocyanidin, essential oils, flavonoids, leucoanthocyanidin, phenols, phytosterols, saponins, simple sugars, terpenoids and triterpenoid have been identified from S. cordatum. Pharmacological evaluations revealed that S. cordatum is characterized by several biological activities including antibacterial, antifungal, antidiarrheal, anti-sexually transmitted infections, antidiabetic, anticholinesterase, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial and anti-proteus. These pharmacological findings lend credence to the traditional ethnomedicinal uses and ethnopharmacological importance of S. cordatum. Future research on the species should identify the biological compounds, their mode of action and physiological pathways and clinical relevance.

  1. Nuclear structure of 231Ac

    International Nuclear Information System (INIS)

    Boutami, R.; Borge, M.J.G.; Mach, H.; Kurcewicz, W.; Fraile, L.M.; Gulda, K.; Aas, A.J.; Garcia-Raffi, L.M.; Lovhoiden, G.; Martinez, T.; Rubio, B.; Tain, J.L.; Tengblad, O.

    2008-01-01

    The low-energy structure of 231 Ac has been investigated by means of γ ray spectroscopy following the β - decay of 231 Ra. Multipolarities of 28 transitions have been established by measuring conversion electrons with a MINI-ORANGE electron spectrometer. The decay scheme of 231 Ra → 231 Ac has been constructed for the first time. The Advanced Time Delayed βγγ(t) method has been used to measure the half-lives of five levels. The moderately fast B(E1) transition rates derived suggest that the octupole effects, albeit weak, are still present in this exotic nucleus

  2. A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbrier Ribeiro, Lyn, E-mail: Lyn.Rosenbrierribeiro@AstraZeneca.com; Ian Storer, R.

    2017-02-15

    Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [{sup 3}H]-NBTI binding affinity (K{sub i}) and [{sup 3}H]-adenosine uptake (IC{sub 50}) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥ 13.3x K{sub i}, ≥ 4x IC{sub 50}) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥ 0.1x K{sub i}, ≥ 0.05x IC{sub 50}) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds K{sub i} < 1 μM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP > 5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders. - Highlights: • ENT1 inhibition causes bronchospasm and severe dyspnoea in respiratory

  3. A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm

    International Nuclear Information System (INIS)

    Rosenbrier Ribeiro, Lyn; Ian Storer, R.

    2017-01-01

    Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [ 3 H]-NBTI binding affinity (K i ) and [ 3 H]-adenosine uptake (IC 50 ) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥ 13.3x K i , ≥ 4x IC 50 ) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥ 0.1x K i , ≥ 0.05x IC 50 ) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds K i < 1 μM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP > 5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders. - Highlights: • ENT1 inhibition causes bronchospasm and severe dyspnoea in respiratory patients. • Neutral or basic

  4. Temporal trends in pharmacology publications by pharmacy institutes: A deeper dig

    OpenAIRE

    Bhatt, Parloop Amit; Patel, Zarana

    2016-01-01

    Objective: Publications in Indian Journal of Pharmacology (IJP) are the face of contemporary pharmacology practices followed in health-care profession - a knowledge-based profession. It depicts trends in terms of quantity (proportions), quality, type (preclinical/clinical), thrust areas, etc., of pharmacology followed by biomedical community professions both nationally and internationally. This article aims to establish temporal trends in pharmacology research by pharmacy institutes in light ...

  5. AC ignition of HID lamps

    NARCIS (Netherlands)

    Sobota, A.; Kanters, J.H.M.; Manders, F.; Veldhuizen, van E.M.; Haverlag, M.

    2010-01-01

    Our aim was to examine the starting behaviour of mid-pressure argon discharges in pin-pin (point-to-point) geometry, typically used in HID lamps. We focused our work on AC ignition of 300 and 700 mbar Ar discharges in Philips 70W standard burners. Frequency was varied between 200 kHz and 1 MHz. In

  6. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

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

  7. Pharmacological therapy for amblyopia

    Science.gov (United States)

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

    2017-01-01

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

  8. 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.

  9. Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

    LENUS (Irish Health Repository)

    Zannad, Faiez

    2011-11-03

    This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the \\'treat-to-target\\' paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and \\'real-world\\' populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

  10. A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum.

    Science.gov (United States)

    Li, Shuping; Cheng, Xuemei; Wang, Changhong

    2017-05-05

    The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research. Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS's dissertations. The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory. Based on this review, there is some evidence for extracts' pharmacological effects on Alzheimer's and Parkinson's diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding

  11. Recent trends in phytochemistry, ethnobotany and pharmacological significance of Alchornea cordifolia (Schumach. & Thonn.) Muell. Arg.

    Science.gov (United States)

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

    2016-09-15

    Alchornea cordifolia (Schumach. & Thonn.) Muell. Arg. (Euphorbiaceae) (A. cordifolia) is widely distributed throughout tropical Africa, where it is used extensively in traditional medicine. Conditions for which the plant has enjoyed wide use are: coughs, gonorrhoea, infertility, prostatitis, bacterial infections, diarrhoea, ulcers, pain, inflammation, fever and bronchial troubles. This review summarizes the achievements of the investigations in traditional uses, ethnobotany, phytochemistry, biological activities and toxicological profile of A. cordifolia; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. A. cordifolia-related information was collected from various resources including published articles in peer-reviewed journals, unpublished materials, textbooks, government survey reports and scientific databases such as Scifinder®, Pubmed, Science Direct, Wiley, Springer, ACS, Scielo, Web of Science and other web search instruments (Google, Yahoo), published on the subject from 1950 to 2016. 'The Plant List' (www.theplantlist.org) and 'Kew Royal Botanic Gardens' (mpns.kew.org) were used to validate the scientific name of the plant. The literature revealed several reports on traditional uses, biological activities, chemical constituents and toxicological evaluation of A. cordifolia. The phytochemical information indicates identification of 95 compounds including fatty acids, terpenoids, flavonoids, phenolic acids, alkaloids, which exhibited various pharmacological activities such as wound healing, anti-inflammation, anticancer, antioxidant, immunomodulation, antidiarrhoeal, antimicrobial, antidepressant, hepatoprotective, antiplasmodial and anxiolytic. However, there are still significant gaps in the completeness of our understanding of A. cordifolia bioactivity, therapeutic value, and roles played by each of the numerous

  12. AcEST: DK954361 [AcEST

    Lifescience Database Archive (English)

    Full Text Available in 5-4 OS=Homo sap... 33 1.1 sp|Q9DBY1|SYVN1_MOUSE E3 ubiquitin-protein ligase synoviolin OS=... 33 1.4 sp|Q...86TM6|SYVN1_HUMAN E3 ubiquitin-protein ligase synoviolin OS=... 33 1.4 sp|O55188|DMP1_MOUSE Dentin matrix ac

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

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

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

  14. Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review

    Science.gov (United States)

    Merlin, Jessica S.; Bulls, Hailey W.; Vucovich, Lee A.; Edelman, E. Jennifer; Starrels, Joanna L.

    2016-01-01

    Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID:27267445

  15. Clinical pharmacology of ifosfamide and metabolites

    NARCIS (Netherlands)

    Kerbusch, T.

    2000-01-01

    Introduction Ifosfamide is an alkylating agent, which is used in the treatment of various types of malignant diseases in adults and childeren. Its use, however, can be accompanied by severe haematological, neuro- and nephrotoxicities. Since its development in the middle of the 1960’s, most of its

  16. Pharmacology and clinical experience with risperidone.

    Science.gov (United States)

    Love, R C; Nelson, M W

    2000-12-01

    Risperidone (Risperdal, Janssen Pharmaceutica) is a second generation antipsychotic (SGA) for the treatment of schizophrenia and other psychotic disorders. It is a potent antagonist of serotonin-2 (5-HT2) and dopamine-2 (D2) receptors in the brain. In comparison to conventional antipsychotics, risperidone demonstrates superior efficacy against the positive and negative symptoms of schizophrenia and a decreased occurrence of extrapyramidal side effects (EPS). Risperidone causes less weight gain than other marketed SGAs, but can increase prolactin levels and cause EPS in a dose-related manner. In a variety of pharmacoeconomic analyses, it has proven to be a cost-effective addition to the antipsychotic armamentarium. As the first SGA available for front line use, risperidone has established a new standard of care for the treatment of individuals with psychotic disorders.

  17. Clinical pharmacology of tiamulin in ruminants.

    Science.gov (United States)

    Ziv, G; Levisohn, S L; Bar-Moshe, B; Bor, A; Soback, S

    1983-03-01

    Median values for the minimum inhibitory concentrations (MIC) of tiamulin for Mycoplasma and Acholeplasma isolated from ruminants were 0.05 micrograms/ml and 0.025 micrograms/ml, respectively. These values were close to the MIC values of tylosin and considerably lower than the respective values for spectinomycin, Spiramycin and oxytetracycline. The serum concentration--time profile of tiamulin after intramuscular (i.m.) injection to goats, ewes, cows and calves, and after oral administration to preruminant calves was characterized by a rapid absorption phase (absorption t1/2 of less than 30 min.), a short plateau phase, an elimination t1/2 ranging between 3 and 6 h, and low peak serum drug levels. The serum elimination t1/2 of the drug after intravenous (i.v.) injection was 25 min. It appears that tiamulin is extensively metabolized in ruminants and is well distributed throughout the body. Drug concentrations in the lungs, liver, and the kidneys 1 h after i.v. injection were four to seven times higher than in blood. The drug penetrated very rapidly into the milk after i.m. administration; mean peak drug concentrations in normal milk and in milk secreted from inflamed glands of cows were 7.5 times and 1.2 times higher respectively, than the mean peak serum drug concentrations. Concentrations of tiamulin of potential therapeutic value in the treatment of mycoplasmal infections can be maintained in the lungs for at least 12 h after i.m. injection at 10 mg/kg, and in preruminant calves after an oral dose of 20 mg/kg. However, tiamulin possesses several very serious side-effects and the i.v. route of administration is definitely contraindicated.

  18. Clinical pharmacology of methadone in dogs.

    Science.gov (United States)

    Ingvast-Larsson, Carina; Holgersson, Anja; Bondesson, Ulf; Lagerstedt, Anne-Sofie; Olsson, Kerstin

    2010-01-01

    To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs. Randomized, cross-over, experimental trial. Nine adult dogs (beagle and beagle cross breeds), four males and five females. Methadone hydrochloride, 0.4 mg kg(-1), was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol. After IV administration, the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL(-1) (mean +/- SD), the terminal half-life was 3.9 +/- 1.0 hours, the volume of distribution 9.2 +/- 3.3 L kg(-1) and plasma clearance 27.9 +/- 7.6 mL minute(-1) kg(-1). After SC administration, time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL(-1), the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic. When methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.

  19. Pharmacological and clinical aspects of thyroid blocking

    International Nuclear Information System (INIS)

    Eickstedt, K.W. von

    1983-01-01

    The paper discusses the risk of uptake of radioactive iodine into the human body. Prevention of iodine - especially 131 I - uptake by the thyroid is a necessary measure in case of reactor accidents, accidental contamination of laboratory staff, and as a preventive measure in patients whose organic functions are studied using 131 I, i.e. in the field of medical diagnostics. The best known thyroid-blocking substance is potassium perchlorate. Perchlorate must be applied in high doses; it is administered when fixed doses of 131 I are applied for a given period of time for diagnostic purposes. In case of reactor accidents, when 131 I is released in uncombined form, potassium iodide is recommended as it has less undesirable side-effects than perchlorate. Further, nothing is known about the effects of short-term high doses of perchlorate. The authors state that the risk of iodine-induced hyperthyroidism is lower with high doses of iodide than with low doses. (orig./MG) [de

  20. Fluoxetine: clinical pharmacology and physiologic disposition

    International Nuclear Information System (INIS)

    Lemberger, L.; Bergstrom, R.F.; Wolen, R.L.; Farid, N.A.; Enas, G.G.; Aronoff, G.R.

    1985-01-01

    Fluoxetine (30 mg), administered for 7 days to normal volunteers, produced a 66% inhibition of tritiated serotonin uptake into platelets. Plasma concentrations of fluoxetine correlated positively with inhibition of serotonin uptake. Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality. Fluoxetine disappears from plasma with a half-life of 1-3 days; its metabolite norfluoxetine has a plasma half-life of 7-15 days. After administration of 14 C-fluoxetine, approximately 65% of the administered dose of radioactivity is recovered in urine and about 15% in feces. Fluoxetine, given as a single dose or in multiple doses over 8 days, did not produce significant effects on the plasma disappearance of warfarin, diazepam, tolbutamide, or chlorothiazide. Coadministration of fluoxetine and ethanol did not result in an increase from control values in the blood ethanol levels, nor did it produce significant changes in physiologic, psychometric, or psychomotor activity. Pharmacokinetics of fluoxetine in the elderly and normal volunteers appear to be similar. In addition, pharmacokinetic analyses in patients with varying degrees of renal impairment did not show significant differences from healthy subjects

  1. Pharmacological Aspects of Neuro-Immune Interactions.

    Science.gov (United States)

    Tarasov, Vadim V; Kudryashov, Nikita V; Chubarev, Vladimir N; Kalinina, Tatiana S; Barreto, George E; Ashraf, Ghulam Md; Aliev, Gjumrakch

    2018-01-01

    The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another. Integrative mechanisms underlying the neuro-immune interactions may explain the "pleiotropic" pharmacological effects of some antiviral and immunomodulatory drugs. Amantadine, which was originally considered as an antiviral agent, was approved as anti-parkinsonic drug after its wide medical use. The prolonged administration of interferon alpha caused depression in 30-45% of patients, thus limiting its clinical use. The antiviral drug "Oseltamivir" may provoke the development of central side effects, including abnormal behavior, delirium, impaired perception and suicides. Anti-herpethetical drug "Panavir" shows pronounced neuroprotective properties. The purpose of this review is to analyze the experimental and clinical data related to central effects of drugs with antiviral or/and immunotropic activity, and to discover the relationship of these effects with changes in reactivity of immune system and proinflammatory response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation.

    Science.gov (United States)

    Ribba, B; Grimm, H P; Agoram, B; Davies, M R; Gadkar, K; Niederer, S; van Riel, N; Timmis, J; van der Graaf, P H

    2017-08-01

    With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  3. 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.

  4. Aperture measurements with AC dipole

    CERN Document Server

    Fuster Martinez, Nuria; Dilly, Joschua Werner; Nevay, Laurence James; Bruce, Roderik; Tomas Garcia, Rogelio; Redaelli, Stefano; Persson, Tobias Hakan Bjorn; CERN. Geneva. ATS Department

    2018-01-01

    During the MDs performed on the 15th of September and 29th of November 2017, we measured the LHC global aperture at injection with a new AC dipole method as well as using the Transverse Damper (ADT) blow-up method used during the 2017 LHC commissioning for benchmarking. In this note, the MD procedure is presented as well as the analysis of the comparison between the two methods. The possible benefits of the new method are discussed.

  5. [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.

  6. Pharmacology of midazolam.

    Science.gov (United States)

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

    1981-01-01

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

  7. Pharmacology of pediatric resuscitation.

    Science.gov (United States)

    Ushay, H M; Notterman, D A

    1997-02-01

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

  8. Urine storage under refrigeration preserves the sample in chemical, cellularity and bacteriuria analysis of ACS

    OpenAIRE

    Karen Cristina Barcellos Ribeiro; Bruno Rotondo Levenhagem Serabion; Eduardo Lima Nolasco; Chislene Pereira Vanelli; Harleson Lopes de Mesquita; José Otávio do Amaral Corrêa

    2013-01-01

    INTRODUCTION: The analysis of urine abnormal constituents and sediment (ACS) comprises tests of great diagnostic and prognostic value in clinical practice. When the analysis of ACS cannot be performed within two hours after collection, the sample must be preserved in order to avoid pre-analytical interferences. Refrigeration is the most applied technique due to its cost effectiveness. Moreover, it presents fewer inconveniences when compared to chemical preservation. However, changes in ACS ma...

  9. Future pharmacological therapy in hypertension.

    Science.gov (United States)

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

    2018-04-26

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

  10. [History and pharmacology of trazodone].

    Science.gov (United States)

    Agnoli, A

    1986-10-01

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

  11. Pharmacological challenges in chronic pancreatitis.

    Science.gov (United States)

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-11-14

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.

  12. Pharmacologic management of chronic neuropathic pain

    Science.gov (United States)

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

    2017-01-01

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

  13. The presence of comorbidity in Tourette syndrome increases the need for pharmacological treatment

    DEFF Research Database (Denmark)

    Debes, Nanette M M M; Hjalgrim, Helle; Skov, Liselotte

    2009-01-01

    to a better insight into the common practice in Scandinavia. Furthermore, we wanted to elaborate the influence of the presence of comorbidities and of the severity of tics on pharmacological treatment. We have examined the frequency, art, and reason for pharmacological treatment in a Danish clinical cohort...... of 314 children with Tourette syndrome. In total, 60.5% of the children once had received pharmacological treatment. Mostly, the treatment was started because of tics or ADHD. If ADHD or obsessive-compulsive disorder were present, more children received pharmacological treatment and more different agents...... were tried. The children who received pharmacological treatment had more severe tics than those without medication....

  14. Simultaneous distribution of AC and DC power

    Science.gov (United States)

    Polese, Luigi Gentile

    2015-09-15

    A system and method for the transport and distribution of both AC (alternating current) power and DC (direct current) power over wiring infrastructure normally used for distributing AC power only, for example, residential and/or commercial buildings' electrical wires is disclosed and taught. The system and method permits the combining of AC and DC power sources and the simultaneous distribution of the resulting power over the same wiring. At the utilization site a complementary device permits the separation of the DC power from the AC power and their reconstruction, for use in conventional AC-only and DC-only devices.

  15. Fuzzy pharmacology: theory and applications.

    Science.gov (United States)

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

    2002-09-01

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

  16. Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Singh

    2017-07-01

    Conclusions: Stimulus and response AC/A ratio increased following VT, accompanied by clinically significant changes in vergence and accommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI.

  17. Pharmacological Overview of Galactogogues

    Directory of Open Access Journals (Sweden)

    Felipe Penagos Tabares

    2014-01-01

    Full Text Available Galactogogues are substances used to induce, maintain, and increase milk production, both in human clinical conditions (like noninfectious agalactias and hypogalactias and in massification of production in the animal dairy industry. This paper aims to report the state of the art on the possible mechanisms of action, effectiveness, and side effects of galactogogues, including potential uses in veterinary and human medicine. The knowledge gaps in veterinary clinical practice use of galactogogues, especially in the standardization of the lactogenic dose in some pure drugs and herbal preparations, are reviewed.

  18. Performance of AC/graphite capacitors at high weight ratios of AC/graphite

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongyu [IM and T Ltd., Advanced Research Center, Saga University, 1341 Yoga-machi, Saga 840-0047 (Japan); Yoshio, Masaki [Advanced Research Center, Department of Applied Chemistry, Saga University, 1341 Yoga-machi, Saga 840-0047 (Japan)

    2008-03-01

    The effect of negative to positive electrode materials' weight ratio on the electrochemical performance of both activated carbon (AC)/AC and AC/graphite capacitors has been investigated, especially in the terms of capacity and cycle-ability. The limited capacity charge mode has been proposed to improve the cycle performance of AC/graphite capacitors at high weight ratios of AC/graphite. (author)

  19. SNS AC Power Distribution and Reliability of AC Power Supply

    CERN Document Server

    Holik, Paul S

    2005-01-01

    The SNS Project has 45MW of installed power. A design description under the Construction Design and Maintenance (CDM) with regard to regulations (OSHA, NFPA, NEC), reliability issues and maintenance of the AC power distribution system are herewith presented. The SNS Project has 45MW of installed power. The Accelerator Systems are Front End (FE)and LINAC KLYSTRON Building (LK), Central Helium Liquefier (CHL), High Energy Beam Transport (HEBT), Accumulator Ring and Ring to Target Beam Transport (RTBT) Support Buildings have 30MW installed power. FELK has 16MW installed, majority of which is klystron and magnet power supply system. CHL, supporting the super conducting portion of the accelerator has 7MW installed power and the RING Systems (HEBT, RING and RTBT) have also 7MW installed power.*

  20. Neuropathic pain in people with cancer (part 2): pharmacological and non-pharmacological management.

    Science.gov (United States)

    Taverner, Tarnia

    2015-08-01

    The aim of this paper is to provide an overview of the management of neuropathic pain associated with cancer and to provide helpful clinical advice for nurses working with patients who may have neuropathic pain. While cancer pain is a mixed-mechanism pain, this article will focus only on neuropathic pain management. The impact of neuropathic pain on patients' quality of life is great and while many patients recover from their cancer, a significant number continue to suffer from a neuropathic pain syndrome. Management of neuropathic pain is significantly different from management of nociceptive pain with respect to pharmacological and non-pharmacological strategies. Neuropathic pain is complex, and as such requires complex management using pharmacological as well as non-pharmacological approaches. Specific drugs for neuropathic pain may be effective for some patients, but not all; therefore, ongoing and comprehensive assessment and management are required. Furthermore, these patients may require trials of several drugs before they find one that works for them. It is important for nurses to understand neuropathic pain, its manifestation, impact on quality of life and management when nursing patients with neuropathic pain associated with cancer.

  1. Factors Affecting the Pharmacology of Antibody–Drug Conjugates

    Directory of Open Access Journals (Sweden)

    Andrew T. Lucas

    2018-02-01

    Full Text Available Major advances in therapeutic proteins, including antibody–drug conjugates (ADCs, have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development.

  2. Interleukin-13-induced MUC5AC is regulated by 15-lipoxygenase 1 pathway in human bronchial epithelial cells.

    Science.gov (United States)

    Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B; O'Donnell, Valerie; Wenzel, Sally E

    2009-05-01

    15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13-induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air-liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma.

  3. PHARMACOLOGY OF CANNABINOIDS

    Directory of Open Access Journals (Sweden)

    Ilonka Ferjan

    2015-06-01

    Full Text Available The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

  4. Clinical application of AcMAR (accelerated multiple-arc radiotherapy) for head and neck tumors. Results of a randomized, two-dose study in Kitami Red-Cross General Hospital

    International Nuclear Information System (INIS)

    Arimoto, Takuro; Yamazaki, Akira; Yonesaka, Akio; Matsuzawa, Tooru; Kanai, Naoki

    2003-01-01

    Enhanced acute mucositis is the limiting factor for accelerated, hyperfractionated radiotherapy in head and neck (H and N) squamous cell carcinomas (SCCs). We have developed a simple, new form of conformal radiotherapy, accelerated multiple arc radiotherapy (AcMAR), which covers the target volume by combined, segmental, and rotational arc fields. Two to three rotational fields were placed with CT guidance, each covering the primary tumor and lymph nodes separately. The optimal inter-isocenter distance was determined by 3D dose calculation. The surface area of oro-pharyngeal mucosa irradiated by more than a 50% dose by this method was reduced by 37-73% compared to that with a conventional parallel opposing technic. Dose searching, randomized two-dose study was initiated in Kitami Red-cross General Hospital (KRCGH) in January 1995, and 101 patients were registered and completed AcMAR in Oct 2000. All the patients were followed for up to 96 months (24-96 mo, median 48 mo) at the time of analysis. Fifty-one out of 101 patients were Stage III (17) and IV (34). Primary site of tumors were; 38 larynx, 25 oropharynx, 15 hypopharynx, 13 oral cavity, and 10 other miscellaneous sites. Patients were randomly allocated either to 60 Gy/24 fr/bid/3 wks to gross tumor volume (GTV) (Group A), or 66 Gy/33 fr/bid/4 wks to GTV (Group B). Forty Gy/16 fr/bid/2 wks was given to the volume of prophylactic'' irradiation in both groups of patients. Results were as follows: All the patients, except for one, completed AcMAR without treatment interruption. Acute mucositis at the site of high-dose irradiation was intense; 72% of Group A and 62.5% of Group B experienced World Health Organization (WHO) Grade 3 (confluent) mucositis focally. Fifty-one out of 53 in Group A and 48/48 in Group B, however, could maintain oral food intake (WHO Grade 1 or 2) even at the peak of their mucositis, because of the limited area of severe mucositis. With regard to late morbidity, however, 6/46 (followed >24 mo

  5. [Pharmacological aspects of pain research in Germany].

    Science.gov (United States)

    Niederberger, E; Kuner, R; Geißlinger, G

    2015-10-01

    In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.

  6. The pharmacological management of metabolic syndrome.

    Science.gov (United States)

    Rask Larsen, Julie; Dima, Lorena; Correll, Christoph U; Manu, Peter

    2018-04-01

    The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice. Areas covered: A Medline literature search was performed to identify clinical trials and meta-analyses related to the therapy of dyslipidemia, arterial hypertension, glucose metabolism and obesity published in the past decade. Expert commentary: Our recommendation for first-line pharmacological are statins for dyslipidemia, renin-angiotensin-aldosteron system inhibitors for arterial hypertension, metformin or sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1RAs) for glucose intolerance, and the GLP-1RA liraglutide for achieving body weight and waist circumference reduction.

  7. Universality of ac conduction in disordered solids

    DEFF Research Database (Denmark)

    Dyre, Jeppe; Schrøder, Thomas

    2000-01-01

    The striking similarity of ac conduction in quite different disordered solids is discussed in terms of experimental results, modeling, and computer simulations. After giving an overview of experiment, a macroscopic and a microscopic model are reviewed. For both models the normalized ac conductivity...... as a function of a suitably scaled frequency becomes independent of details of the disorder in the extreme disorder limit, i.e., when the local randomly varying mobilities cover many orders of magnitude. The two universal ac conductivities are similar, but not identical; both are examples of unusual non......-power-law universalities. It is argued that ac universality reflects an underlying percolation determining dc as well as ac conductivity in the extreme disorder limit. Three analytical approximations to the universal ac conductivities are presented and compared to computer simulations. Finally, model predictions...

  8. The AC photovoltaic module is here!

    Science.gov (United States)

    Strong, Steven J.; Wohlgemuth, John H.; Wills, Robert H.

    1997-02-01

    This paper describes the design, development, and performance results of a large-area photovoltaic module whose electrical output is ac power suitable for direct connection to the utility grid. The large-area ac PV module features a dedicated, integrally mounted, high-efficiency dc-to-ac power inverter with a nominal output of 250 watts (STC) at 120 Vac, 60 H, that is fully compatible with utility power. The module's output is connected directly to the building's conventional ac distribution system without need for any dc wiring, string combiners, dc ground-fault protection or additional power-conditioning equipment. With its advantages, the ac photovoltaic module promises to become a universal building block for use in all utility-interactive PV systems. This paper discusses AC Module design aspects and utility interface issues (including islanding).

  9. Study on ac losses of HTS coil carrying ac transport current

    International Nuclear Information System (INIS)

    Dai Taozhen; Tang Yuejin; Li Jingdong; Zhou Yusheng; Cheng Shijie; Pan Yuan

    2005-01-01

    Ac loss has an important influence on the thermal performances of HTS coil. It is necessary to quantify ac loss to ascertain its impact on coil stability and for sizing the coil refrigeration system. In this paper, we analyzed in detail the ac loss components, hysteresis loss, eddy loss and flux flow loss in the pancake HTS coil carrying ac transport current by finite element method. We also investigated the distribution of the ac losses in the coil to study the effects of magnetic field distribution on ac losses

  10. RHIC spin flipper AC dipole controller

    Energy Technology Data Exchange (ETDEWEB)

    Oddo, P.; Bai, M.; Dawson, C.; Gassner, D.; Harvey, M.; Hayes, T.; Mernick, K.; Minty, M.; Roser, T.; Severino, F.; Smith, K.

    2011-03-28

    The RHIC Spin Flipper's five high-Q AC dipoles which are driven by a swept frequency waveform require precise control of phase and amplitude during the sweep. This control is achieved using FPGA based feedback controllers. Multiple feedback loops are used to and dynamically tune the magnets. The current implementation and results will be presented. Work on a new spin flipper for RHIC (Relativistic Heavy Ion Collider) incorporating multiple dynamically tuned high-Q AC-dipoles has been developed for RHIC spin-physics experiments. A spin flipper is needed to cancel systematic errors by reversing the spin direction of the two colliding beams multiple times during a store. The spin flipper system consists of four DC-dipole magnets (spin rotators) and five AC-dipole magnets. Multiple AC-dipoles are needed to localize the driven coherent betatron oscillation inside the spin flipper. Operationally the AC-dipoles form two swept frequency bumps that minimize the effect of the AC-dipole dipoles outside of the spin flipper. Both AC bumps operate at the same frequency, but are phase shifted from each other. The AC-dipoles therefore require precise control over amplitude and phase making the implementation of the AC-dipole controller the central challenge.

  11. Acanthopanax senticosus: review of botany, chemistry and pharmacology.

    Science.gov (United States)

    Huang, Linzhang; Zhao, Hongfang; Huang, Baokang; Zheng, Chengjian; Peng, Wei; Qin, Luping

    2011-02-01

    Acanthopanax senticosus (Rupr. et Maxim) Harms (Araliaceae), also called Siberian Ginseng, Eleutherococcus senticosus, and Ciwujia in Chinese, is a widely used traditional Chinese herb that could invigorate qi, strengthen the spleen, and nourish kidney in the theory of Traditional Chinese Medicine. With high medicinal value, Acanthopanax senticosus (AS, thereafter) is popularly used as an "adaptogen" like Panax ginseng. In recent decades, a great number of chemical, pharmacological, and clinical studies on AS have been carried out worldwide. Several kinds of chemical compounds have been reported, including triterpenoid saponins, lignans, coumarins, and flavones, among which, phenolic compounds such as syringin and eleutheroside E, were considered to be the most active components. Considerable pharmacological experiments both in vitro and in vivo have persuasively demonstrated that AS possessed anti-stress, antiulcer, anti-irradiation, anticancer, anti-inflammatory and hepatoprotective activities, etc. The present review is an up-to-date and comprehensive analysis of the botany, chemistry, pharmacology, toxicity and clinical trials of AS.

  12. Pharmacology of anabolic steroids.

    Science.gov (United States)

    Kicman, A T

    2008-06-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

  13. Contemporary pharmacological obesity treatments

    Directory of Open Access Journals (Sweden)

    Kaszubska Katarzyna

    2016-06-01

    Full Text Available In the last few years, obesity has become a global epidemic. Consequently, worldwide costs associated with managing obesity and obesity-related comorbidities are huge. Numerous studies have focused on discerning the appropriate proper treatment of weight related problems such as overweight and obesity. Moreover, many clinical trials have been conducted for many years in order to introduce effective anti-obesity drugs. The aim of the present review is to provide an overview of current and future pharmacotherapy for obesity, and to provide the reader with a determination of the concentration and composition of long and short term anti-obesity drugs, doing so by placing emphasis on pharmacotherapy and up-to-day solutions. It should be noted that, currently, the worldwide pharmacotherapy is represented by phendimetrazine, benzphetamine and diethylpropion, as well as by orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide. In our paper, individual cases of patients’ needs are thoroughly illustrated by way of examples. Medical prescriptions and contraindications are also described.

  14. Pharmacology Experiments on the Computer.

    Science.gov (United States)

    Keller, Daniel

    1990-01-01

    A computer program that replaces a set of pharmacology and physiology laboratory experiments on live animals or isolated organs is described and illustrated. Five experiments are simulated: dose-effect relationships on smooth muscle, blood pressure and catecholamines, neuromuscular signal transmission, acetylcholine and the circulation, and…

  15. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  16. Chemotaxonomy and pharmacology of Gentianaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Schripsema, Jan

    2002-01-01

    the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....

  17. A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

    Science.gov (United States)

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-04-01

    At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.

  18. Pharmacological management of spasticity in multiple sclerosis

    DEFF Research Database (Denmark)

    Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo

    2016-01-01

    Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods...... improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity...... and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence...

  19. Bioinformatics and Astrophysics Cluster (BinAc)

    Science.gov (United States)

    Krüger, Jens; Lutz, Volker; Bartusch, Felix; Dilling, Werner; Gorska, Anna; Schäfer, Christoph; Walter, Thomas

    2017-09-01

    BinAC provides central high performance computing capacities for bioinformaticians and astrophysicists from the state of Baden-Württemberg. The bwForCluster BinAC is part of the implementation concept for scientific computing for the universities in Baden-Württemberg. Community specific support is offered through the bwHPC-C5 project.

  20. High-Throughput Screening of Ototoxic and Otoprotective Pharmacological Drugs

    Science.gov (United States)

    Kalinec, Federico

    2005-01-01

    Drug ototoxicity research has relied traditionally on animal models for the discovery and development of therapeutic interventions. More than 50 years of research, however, has delivered few--if any--successful clinical strategies for preventing or ameliorating the ototoxic effects of common pharmacological drugs such as aminoglycoside…

  1. Integrated quantitative pharmacology for treatment optimization in oncology

    NARCIS (Netherlands)

    van Hasselt, J.G.C.

    2014-01-01

    This thesis describes the development and application of quantitative pharmacological models in oncology for treatment optimization and for the design and analysis of clinical trials with respect to pharmacokinetics, toxicity, efficacy and cost-effectiveness. A recurring theme throughout this thesis

  2. Pharmacological interventions for acute pancreatitis.

    Science.gov (United States)

    Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2017-04-21

    the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

  3. Noradrenergic augmentation strategies in the pharmacological treatment of depression and schizophrenia : An experimental study

    OpenAIRE

    Linnér, Love

    2002-01-01

    The pharmacological treatment of depression and schizophrenia, two major psychiatric disorders, is largely based on modulation of central monoaminergic neurotransmission. However, currently available pharmacological treatment alternatives possess a relatively modest clinical efficacy, making them less than optimal. The present series of studies, using in vivo electrophysiological, biochemical and behavioral techniques in rats, aim at the disclosure of mechanisms whereby an ...

  4. Multiple sclerosis: general features and pharmacologic approach

    International Nuclear Information System (INIS)

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

    2009-01-01

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

  5. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

    Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.

  6. Harnessing Big Data for Systems Pharmacology.

    Science.gov (United States)

    Xie, Lei; Draizen, Eli J; Bourne, Philip E

    2017-01-06

    Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.

  7. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  8. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  9. Pharmacological properties of Salvia officinalis and its components

    Directory of Open Access Journals (Sweden)

    Ahmad Ghorbani

    2017-10-01

    Full Text Available Salvia officinalis (Sage is a plant in the family of Labiatae/Lamiaceae. It is native to Middle East and Mediterranean areas, but today has been naturalized throughout the world. In folk medicine, S. officinalis has been used for the treatment of different kinds of disorders including seizure, ulcers, gout, rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and hyperglycemia. In recent years, this plant has been a subject of intensive studies to document its traditional use and to find new biological effects. These studies have revealed a wide range of pharmacological activities for S. officinalis. Present review highlights the up-to-date information on the pharmacological findings that have been frequently reported for S. officinalis. These findings include anticancer, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects. Also, chemical constituents responsible for pharmacological effects of S. officinalis and the clinical studies on this plant are presented and discussed.

  10. Current trends and future development in pharmacologic stress testing

    International Nuclear Information System (INIS)

    Bae, Jin Ho; Lee, Jae Tae

    2005-01-01

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

  11. 78 FR 49318 - Availability of Draft Advisory Circular (AC) 90-106A and AC 20-167A

    Science.gov (United States)

    2013-08-13

    ...] Availability of Draft Advisory Circular (AC) 90-106A and AC 20- 167A AGENCY: Federal Aviation Administration... of draft Advisory Circular (AC) 90-106A, Enhanced Flight Vision Systems and draft AC 20- 167A... Federal holidays. FOR FURTHER INFORMATION CONTACT: For technical questions concerning draft AC 90-106A...

  12. A Correction Formula for the ST Segment Measurements for the AC-coupled Electrocardiograms

    DEFF Research Database (Denmark)

    Schmid, Ramun; Isaksen, Jonas; Leber, Remo

    2017-01-01

    Goal: The ST segment of an electrocardiogram (ECG) is very important for the correct diagnosis of an acute myocardial infarction. Most clinical ECGs are recorded using an AC-coupled ECG amplifier. It is well known, that first-order high-pass filters used for the AC coupling can affect the ST...... segment of an ECG. This effect is stronger the higher the filter's cut-off frequency is and the larger the QRS integral is. We present a formula that estimates these changes in the ST segment and therefore allows for correcting ST measurements that are based on an AC-coupled ECG. Methods: The presented...

  13. AC distribution system for TFTR pulsed loads

    International Nuclear Information System (INIS)

    Carroll, R.F.; Ramakrishnan, S.; Lemmon, G.N.; Moo, W.I.

    1977-01-01

    This paper outlines the AC distribution system associated with the Tokamak Fusion Test Reactor and discusses the significant areas related to design, protection, and equipment selection, particularly where there is a departure from normal utility and industrial applications

  14. Nonlinear AC susceptibility, surface and bulk shielding

    Science.gov (United States)

    van der Beek, C. J.; Indenbom, M. V.; D'Anna, G.; Benoit, W.

    1996-02-01

    We calculate the nonlinear AC response of a thin superconducting strip in perpendicular field, shielded by an edge current due to the geometrical barrier. A comparison with the results for infinite samples in parallel field, screened by a surface barrier, and with those for screening by a bulk current in the critical state, shows that the AC response due to a barrier has general features that are independent of geometry, and that are significantly different from those for screening by a bulk current in the critical state. By consequence, the nonlinear (global) AC susceptibility can be used to determine the origin of magnetic irreversibility. A comparison with experiments on a Bi 2Sr 2CaCu 2O 8+δ crystal shows that in this material, the low-frequency AC screening at high temperature is mainly due to the screening by an edge current, and that this is the unique source of the nonlinear magnetic response at temperatures above 40 K.

  15. Logistics Reduction: Advanced Clothing System (ACS)

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of the Advanced Exploration System (AES) Logistics Reduction (LR) project's Advanced Clothing System (ACS) is to use advanced commercial off-the-shelf...

  16. Pharmacological chaperoning: a primer on mechanism and pharmacology.

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

    Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

  17. 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.

  18. Targeting HIV latency: pharmacologic strategies toward eradication

    Science.gov (United States)

    Xing, Sifei; Siliciano, Robert F.

    2013-01-01

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

  19. Marketingová komunikace AC Sparta Praha

    OpenAIRE

    Fanta, Jan

    2016-01-01

    Title: Marketing communications of AC Sparta Praha Objectives: The main objective of this thesis is to analyze contemporary state of marketing communications with the audience of AC Sparta Praha, identify deficiencies and develop a proposal to improve the marketing communications with fans of this club. Methods: In this thesis have been used methods of case study, analysis of available documents and texts, structured interview with director od marketing, and director of communications and pub...

  20. Cooperative Frequency Control for Autonomous AC Microgrids

    DEFF Research Database (Denmark)

    Shafiee, Qobad; Quintero, Juan Carlos Vasquez; Guerrero, Josep M.

    2015-01-01

    Distributed secondary control strategies have been recently studied for frequency regulation in droop-based AC Microgrids. Unlike centralized secondary control, the distributed one might fail to provide frequency synchronization and proportional active power sharing simultaneously, due to having...... not require measuring the system frequency as compared to the other presented methods. An ac Microgrid with four sources is used to verify the performance of the proposed control methodology....

  1. Transport AC losses in YBCO coated conductors

    Energy Technology Data Exchange (ETDEWEB)

    Majoros, M [Ohio State University, Columbus, OH 43210 (United States); Ye, L [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Velichko, A V [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Coombs, T A [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Sumption, M D [Ohio State University, Columbus, OH 43210 (United States); Collings, E W [Ohio State University, Columbus, OH 43210 (United States)

    2007-09-15

    Transport AC loss measurements have been made on YBCO-coated conductors prepared on two different substrate templates-RABiTS (rolling-assisted biaxially textured substrate) and IBAD (ion-beam-assisted deposition). RABiTS samples show higher losses compared with the theoretical values obtained from the critical state model, with constant critical current density, at currents lower than the critical current. An origin of this extra AC loss was demonstrated experimentally by comparison of the AC loss of two samples with different I-V curves. Despite a difference in I-V curves and in the critical currents, their measured losses, as well as the normalized losses, were practically the same. However, the functional dependence of the losses was affected by the ferromagnetic substrate. An influence of the presence of a ferromagnetic substrate on transport AC losses in YBCO film was calculated numerically by the finite element method. The presence of a ferromagnetic substrate increases transport AC losses in YBCO films depending on its relative magnetic permeability. The two loss contributions-transport AC loss in YBCO films and ferromagnetic loss in the substrate-cannot be considered as mutually independent.

  2. Proportional-Integral-Resonant AC Current Controller

    Directory of Open Access Journals (Sweden)

    STOJIC, D.

    2017-02-01

    Full Text Available In this paper an improved stationary-frame AC current controller based on the proportional-integral-resonant control action (PIR is proposed. Namely, the novel two-parameter PIR controller is applied in the stationary-frame AC current control, accompanied by the corresponding parameter-tuning procedure. In this way, the proportional-resonant (PR controller, common in the stationary-frame AC current control, is extended by the integral (I action in order to enable the AC current DC component tracking, and, also, to enable the DC disturbance compensation, caused by the voltage source inverter (VSI nonidealities and by nonlinear loads. The proposed controller parameter-tuning procedure is based on the three-phase back-EMF-type load, which corresponds to a wide range of AC power converter applications, such as AC motor drives, uninterruptible power supplies, and active filters. While the PIR controllers commonly have three parameters, the novel controller has two. Also, the provided parameter-tuning procedure needs only one parameter to be tuned in relation to the load and power converter model parameters, since the second controller parameter is directly derived from the required controller bandwidth value. The dynamic performance of the proposed controller is verified by means of simulation and experimental runs.

  3. Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department

    Directory of Open Access Journals (Sweden)

    E. Sánchez Gómez

    2014-07-01

    Full Text Available Abstract: Objective: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. Material and methods: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE® and EMBASE® (with the filer language English or Spanish, and the descriptors: “name of the anti-cancer drug” AND (“drug interactions” OR “pharmacokinetic”, Up-to-date®, MICROMEDEX® and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction-free alternative was sought. Results: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts and Hypericum perforatum. Conclusions: Oral anticancer drugs have numerous pharmacologic

  4. Herbal Medicine AC591 Prevents Oxaliplatin-Induced Peripheral Neuropathy in Animal Model and Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xiaolan Cheng

    2017-06-01

    Full Text Available Oxaliplatin is clinically compelling because of severe peripheral neuropathy. The side effect can result in dosage reductions or even cessation of chemotherapy, and no effective treatments are available. AC591 is a standardized extract of Huangqi Guizhi Wuwu decoction, an herbal formula recorded in “Synopsis of the Golden Chamber” for improving limb numbness and pain. In this study, we investigated whether AC591 could protect against oxaliplatin-induced peripheral neuropathy. To clarify it, a rat model of oxaliplatin-induced peripheral neuropathy was established, and neuroprotective effect of AC591 was studied. Our results showed that pretreatment with AC591 reduced oxaliplatin-induced cold hyperalgesia, mechanical allodynia as well as morphological damage of dorsal root ganglion. Microarray analysis indicated the neuroprotective action of AC591 depended on the modulation of multiple molecular targets and pathways involved in the downregulation of inflammation and immune response. Moreover, AC591 enhanced the antitumor activity of oxaliplatin to some extent in Balb/c mice bearing CT-26 carcinoma cells. The efficacy of AC591 is also investigated in 72 colorectal cancer patients. After four cycles of treatment, the percentage of grades 1–2 neurotoxicity in AC591-treated group (n = 36 was 25%, whereas in the control group the incidence was 55.55% (P < 0.01 (n = 36. No significant differences in the tumor response rate between the two groups were found. These evidences suggested that AC591 can prevent oxaliplatin-induced neuropathy without reducing its antitumor activity, and may be a promising adjuvant to alleviate sensory symptoms in clinical practice.

  5. The Effect of the Feedback Controller on Superconducting Tokamak AC Losses + AC-CRPP user manual

    International Nuclear Information System (INIS)

    Schaerz, B.; Bruzzone, P.; Favez, J.Y.; Lister, J.B.; Zapretilina, E.

    2001-11-01

    Superconducting coils in a Tokamak are subject to AC losses when the field transverse to the coil current varies. A simple model to evaluate the AC losses has been derived and benchmarked against a complete model used in the ITER design procedure. The influence of the feedback control strategy on the AC losses is examined using this model. An improved controller is proposed, based on this study. (author)

  6. The Role of Pharmacology in Ureteral Physiology and Expulsive Therapy

    Science.gov (United States)

    Jerde, Travis J.; Nakada, Stephen Y.

    2007-04-01

    Research in the field of ureteral physiology and pharmacology has traditionally been directed toward relaxation of ureteral spasm as a mechanism of analgesia during painful ureteral obstruction, most often stone-induced episodes. However, interest in this field has expanded greatly in recent years with the expanded use of alpha-blocker therapy for inducing stone passage, a usage now termed "medical expulsive therapy". While most clinical reports involving expulsive therapy have focused on alpha receptor or calcium channel blockade, there are diverse studies investigating pharmacological ureteral relaxation with novel agents including cyclooxygenase inhibitors, small molecule beta receptor agonists, neurokinin antagonists, and phosphodiesterase inhibitors. In addition, cutting edge molecular biology research is revealing promising potential therapeutic targets aimed at specific molecular changes that occur during the acute obstruction that accompanies stone disease. The purpose of this report is to review the use of pharmacological agents as ureteral smooth muscle relaxants clinically, and to look into the future of expulsive therapy by reviewing the available literature of ureteral physiology and pharmacology research.

  7. Gaultheria: Phytochemical and Pharmacological Characteristics

    Directory of Open Access Journals (Sweden)

    Ren-Bing Shi

    2013-09-01

    Full Text Available The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C6-C3 constituents, organic acids, terpenoids, steroids, and other compounds. Methyl salicylate glycoside is considered as a characteristic ingredient in this genus, whose anti-rheumatic effects may have a new mechanism of action. In this review, comprehensive information on the phytochemistry, volatile components and the pharmacology of the genus Gaultheria is provided to explore its potential and advance research.

  8. O tratamento farmacológico do transtorno bipolar: uma revisão sistemática e crítica dos aspectos metodológicos dos estudos clínicos modernos The pharmacological treatment of bipolar disorder: a systematic and critical review of the methodological aspects of modern clinical trials

    Directory of Open Access Journals (Sweden)

    Elie Cheniaux

    2011-03-01

    Full Text Available OBJETIVO: Revisar sistematicamente os principais estudos clínicos sobre o tratamento farmacológico do transtorno bipolar e fazer uma análise crítica de seus aspectos metodológicos. MÉTODO: Realizou-se uma busca nas bases de dados Medline, ISI e PsycINFO, utilizando-se os seguintes termos de busca: "bipolar", "randomized", "placebo" e "controlled". Foram selecionados estudos clínicos randomizados, duplo-cegos e controlados por placebo sobre o tratamento farmacológico do transtorno bipolar. Além disso, de acordo com os nossos critérios, as amostras deveriam ser de no mínimo 100 pacientes e a substância testada deveria ser usada como monoterapia. RESULTADOS: 34 artigos se adequaram aos critérios de seleção. Todas as substâncias atualmente indicadas para mania, depressão bipolar e para o tratamento de manutenção foram mais eficazes que o placebo em pelo menos um estudo. Todavia, esses estudos tiveram amostras altamente selecionadas, altas taxas de abandono e baixas taxas de resposta clínica. CONCLUSÃO: Os modernos estudos clínicos sobre o tratamento farmacológico do transtorno bipolar apresentam algumas importantes limitações metodológicas. Assim, seus resultados devem ser considerados com cautela.OBJECTIVE: To review systematically the main clinical trials on the pharmacological treatment of bipolar disorder and to make a critical analysis of their methodological aspects. METHOD: A search in Medline, ISI and PsycINFO databases was conducted, using the following search terms: "bipolar", "randomized", "placebo" e "controlled". Randomized, double-blind, placebo-controlled clinical trials on the pharmacological treatment of bipolar disorder were selected. Besides, according to our criteria, samples had to consist of at least 100 patients and experimental drug had to be used as monotherapy. RESULTS: 34 articles met our selection criteria. All drugs currently indicated for mania, bipolar depression and maintenance treatment of

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

    Directory of Open Access Journals (Sweden)

    Luiza R. Nazario

    2017-11-01

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

  10. Pharmacological treatment of cardiac glycoside poisoning.

    Science.gov (United States)

    Roberts, Darren M; Gallapatthy, Gamini; Dunuwille, Asunga; Chan, Betty S

    2016-03-01

    Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. Poisoning can manifest as varying degrees of toxicity. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Death occurs from ventricular fibrillation or tachycardia. A wide range of treatments have been used, the more common including activated charcoal, atropine, β-adrenoceptor agonists, temporary pacing, anti-digoxin Fab and magnesium, and more novel agents include fructose-1,6-diphosphate (clinical trial in progress) and anticalin. However, even in the case of those treatments that have been in use for decades, there is debate regarding their efficacy, the indications and dosage that optimizes outcomes. This contributes to variability in use across the world. Another factor influencing usage is access. Barriers to access include the requirement for transfer to a specialized centre (for example, to receive temporary pacing) or financial resources (for example, anti-digoxin Fab in resource poor countries). Recent data suggest that existing methods for calculating the dose of anti-digoxin Fab in digoxin poisoning overstate the dose required, and that its efficacy may be minimal in patients with chronic digoxin poisoning. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries. © 2015 The British Pharmacological Society.

  11. Safety pharmacology — Current and emerging concepts

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  12. Safety pharmacology — Current 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. Êxtase (MDMA: efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica Ecstasy (MDMA: pharmacological and toxic effects, mechanism of action and clinical management

    Directory of Open Access Journals (Sweden)

    Caroline Addison Carvalho Xavier

    2008-01-01

    Full Text Available CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável.BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985

  14. Radioimmunoassay in clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Ametov, A S

    1982-01-01

    A wide application of radioimmunoassay in clinical practice is shown. The main theoretical aspects of radioimmunoassay and the fields of application in clinical practice - endocrinology, oncology, allergology, cardiology, pharmacology, pediatrics, hematology, obstetrics and gynecology, are presented.

  15. The Effectiveness of Pharmacological and Non-Pharmacological Interventions for Improving Glycaemic Control in Adults with Severe Mental Illness: A Systematic Review and Meta-Analysis

    OpenAIRE

    Taylor, Johanna; Stubbs, Brendon; Hewitt, Catherine; Ajjan, Ramzi A.; Alderson, Sarah L.; Gilbody, Simon; Holt, Richard I. G.; Hosali, Prakash; Hughes, Tom; Kayalackakom, Tarron; Kellar, Ian; Lewis, Helen; Mahmoodi, Neda; McDermid, Kirstine; Smith, Robert D.

    2017-01-01

    People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs...

  16. Design and synthesis of 225Ac radioimmunopharmaceuticals

    International Nuclear Information System (INIS)

    McDevitt, Michael R.; Ma, Dangshe; Simon, Jim; Frank, R. Keith; Scheinberg, David A.

    2002-01-01

    The alpha-particle-emitting radionuclides 213 Bi, 211 At, 224 Ra are under investigation for the treatment of leukemias, gliomas, and ankylosing spondylitis, respectively. 213 Bi and 211 At were attached to monoclonal antibodies and used as targeted immunotherapeutic agents while unconjugated 224 Ra chloride selectively seeks bone. 225 Ac possesses favorable physical properties for radioimmunotherapy (10 d half-life and 4 net alpha particles), but has a history of unfavorable radiolabeling chemistry and poor metal-chelate stability. We selected functionalized derivatives of DOTA as the most promising to pursue from out of a group of potential 225 Ac chelate compounds. A two-step synthetic process employing either MeO-DOTA-NCS or 2B-DOTA-NCS as the chelating moiety was developed to attach 225 Ac to monoclonal antibodies. This method was tested using several different IgG systems. The chelation reaction yield in the first step was 93±8% radiochemically pure (n=26). The second step yielded 225 Ac-DOTA-IgG constructs that were 95±5% radiochemically pure (n=27) and the mean percent immunoreactivity ranged from 25% to 81%, depending on the antibody used. This process has yielded several potential novel targeted 225 Ac-labeled immunotherapeutic agents that may now be evaluated in appropriate model systems and ultimately in humans

  17. Pharmacological and non- pharmacological treatment of hypertension: A review article

    Directory of Open Access Journals (Sweden)

    Marjan Seyedmazhari

    2013-01-01

    Full Text Available BACKGROUND: Hypertension is a worldwide epidemic disease. It is more common and more severe in elderly persons. Various studies however have estimated 41.9 million men and 27.8 million women to have prehypertension. Diagnosis and early treatment of prehypertension are of utmost importance. Although hypertension is usually divided into 2 general categories of essential (primary and secondary hypertension, the initial treatment for hypertension often depends on its stage which is determined by systolic and diastolic blood pressure. Lifestyle modification is the first step in treating stage one hypertension. Pharmaceutical treatments including diuretics, angiotensin converting enzyme (ACE inhibitors, calcium blockers, beta blockers, and angiotensin receptor blockers will be recommended if lifestyle modification fails to control blood pressure.    METHODS: The PubMed database was searched by a number of keywords including hypertension, pharmaceutical treatment, and non-pharmaceutical treatment. The results were limited by determining a date range of 2008-11.    RESULTS: High blood pressure causes major health problems for many people around the world. It should be controlled because of its high mortality and morbidity. However, in order to select an appropriate treatment modality, it is initially important to diagnose the kinds and stages of hypertension. Pharmaceutical or non-pharmaceutical treatments can then be employed to control this serious disease.    CONCLUSION: Treating hypertension depends on the kinds and stages of this disease. Several tips should be considered when selecting a method of treatment.       Keywords: Hypertension, Pharmacological treatment, Non-pharmacological treatment

  18. Approaches to building single-stage AC/AC conversion switch-mode audio power amplifiers

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2004-01-01

    This paper discusses the possible topologies and promising approaches towards direct single-phase AC-AC conversion of the mains voltage for audio applications. When compared to standard Class-D switching audio power amplifiers with a separate power supply, it is expected that direct conversion...

  19. ac propulsion system for an electric vehicle

    Science.gov (United States)

    Geppert, S.

    1980-01-01

    It is pointed out that dc drives will be the logical choice for current production electric vehicles (EV). However, by the mid-80's, there is a good chance that the price and reliability of suitable high-power semiconductors will allow for a competitive ac system. The driving force behind the ac approach is the induction motor, which has specific advantages relative to a dc shunt or series traction motor. These advantages would be an important factor in the case of a vehicle for which low maintenance characteristics are of primary importance. A description of an EV ac propulsion system is provided, taking into account the logic controller, the inverter, the motor, and a two-speed transmission-differential-axle assembly. The main barrier to the employment of the considered propulsion system in EV is not any technical problem, but inverter transistor cost.

  20. Superconducting three element synchronous ac machine

    International Nuclear Information System (INIS)

    Boyer, L.; Chabrerie, J.P.; Mailfert, A.; Renard, M.

    1975-01-01

    There is a growing interest in ac superconducting machines. Of several new concepts proposed for these machines in the last years one of the most promising seems to be the ''three elements'' concept which allows the cancellation of the torque acting on the superconducting field winding, thus overcoming some of the major contraints. This concept leads to a device of induction-type generator. A synchronous, three element superconducting ac machine is described, in which a room temperature, dc fed rotating winding is inserted between the superconducting field winding and the ac armature. The steady-state machine theory is developed, the flux linkages are established, and the torque expressions are derived. The condition for zero torque on the field winding, as well as the resulting electrical equations of the machine, are given. The theoretical behavior of the machine is studied, using phasor diagrams and assuming for the superconducting field winding either a constant current or a constant flux condition

  1. 21 CFR 886.4440 - AC-powered magnet.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AC-powered magnet. 886.4440 Section 886.4440 Food... DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4440 AC-powered magnet. (a) Identification. An AC-powered magnet is an AC-powered device that generates a magnetic field intended to find and remove...

  2. Physiological and Pharmacological Aspects of the Vas Deferens - an Update

    Directory of Open Access Journals (Sweden)

    David Stewart Koslov

    2013-08-01

    Full Text Available The vas deferens, a muscular conduit conveying spermatozoa from the epididymis to the urethra, has been used as a model tissue for smooth muscle pharmacological and physiological advancements. Many drugs, notably α-adrenergic antagonists, have effects on contractility and thus normal ejaculation, incurring significant side effects for patients that may interfere with compliance. A more thorough understanding of the innervation and neurotransmitter pharmacology of the vas has indicated that this is a highly complex structure and a model for co-transmission at the synapse. Recent models have shown clinical scenarios that alter the vas contraction. This review covers structure, receptors, neurotransmitters, smooth muscle physiology, and clinical implications of the vas deferens.

  3. AC conductivity for a holographic Weyl semimetal

    Energy Technology Data Exchange (ETDEWEB)

    Grignani, Gianluca; Marini, Andrea; Peña-Benitez, Francisco; Speziali, Stefano [Dipartimento di Fisica e Geologia, Università di Perugia,I.N.F.N. Sezione di Perugia,Via Pascoli, I-06123 Perugia (Italy)

    2017-03-23

    We study the AC electrical conductivity at zero temperature in a holographic model for a Weyl semimetal. At small frequencies we observe a linear dependence in the frequency. The model shows a quantum phase transition between a topological semimetal (Weyl semimetal phase) with a non vanishing anomalous Hall conductivity and a trivial semimetal. The AC conductivity has an intermediate scaling due to the presence of a quantum critical region in the phase diagram of the system. The phase diagram is reconstructed using the scaling properties of the conductivity. We compare with the experimental data of https://www.doi.org/10.1103/PhysRevB.93.121110 obtaining qualitative agreement.

  4. Mapa acústico parcial de Benetusser

    OpenAIRE

    MORILLA CASTELLANOS, EMILIO

    2012-01-01

    Se establece el mapa de ruido del municipio de Benetússer para evaluar y conocer su exposición al ruido ambiental y así poder dar cumplimiento a la Directiva Europea sobre Gestión y Evaluación de Ruido Ambiental (2002/49/CE) y a la Ley nacional 37/2003 del Ruido. Los mapas estratégicos de ruido nos aportan la información fundamental para diagnosticar la situación acústica y para la gestión del ruido ambiental. Morilla Castellanos, E. (2012). Mapa acústico parcial de Benetusser. http://h...

  5. Preliminary study on AC superconducting machines

    International Nuclear Information System (INIS)

    Yamamoto, M.; Ishigohka, T.; Shimohka, T.; Mizukami, N.; Yamaguchi, M.

    1988-01-01

    This paper describes the issues involved in developing AC superconducting machines. In the first phase, as a preliminary experiment, a 4kVa AC superconducting coil which employs 100A class 50/60Hz superconductors is made and tested. And, in the second phase, as an extension of the 4kVa coil, a model superconducting transformer is made and examined. The transformer has a novel quench protection system with an auxiliary coil only in the low voltage side. The behavior of the overcurrent protection system is confirmed

  6. Nuclear structure of {sup 231}Ac

    Energy Technology Data Exchange (ETDEWEB)

    Boutami, R. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain); Borge, M.J.G. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain)], E-mail: borge@iem.cfmac.csic.es; Mach, H. [Department of Radiation Sciences, ISV, Uppsala University, SE-751 21 Uppsala (Sweden); Kurcewicz, W. [Department of Physics, University of Warsaw, Pl-00 681 Warsaw (Poland); Fraile, L.M. [Departamento Fisica Atomica, Molecular y Nuclear, Facultad CC. Fisicas, Universidad Complutense, E-28040 Madrid (Spain); ISOLDE, PH Department, CERN, CH-1211 Geneva 23 (Switzerland); Gulda, K. [Department of Physics, University of Warsaw, Pl-00 681 Warsaw (Poland); Aas, A.J. [Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo (Norway); Garcia-Raffi, L.M. [Instituto de Fisica Corpuscular, CSIC - Universidad de Valencia, Apdo. 22805, E-46071 Valencia (Spain); Lovhoiden, G. [Department of Physics, University of Oslo, PO Box 1048, Blindern, N-0316 Oslo (Norway); Martinez, T.; Rubio, B.; Tain, J.L. [Instituto de Fisica Corpuscular, CSIC - Universidad de Valencia, Apdo. 22805, E-46071 Valencia (Spain); Tengblad, O. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain); ISOLDE, PH Department, CERN, CH-1211 Geneva 23 (Switzerland)

    2008-10-15

    The low-energy structure of {sup 231}Ac has been investigated by means of {gamma} ray spectroscopy following the {beta}{sup -} decay of {sup 231}Ra. Multipolarities of 28 transitions have been established by measuring conversion electrons with a MINI-ORANGE electron spectrometer. The decay scheme of {sup 231}Ra {yields}{sup 231}Ac has been constructed for the first time. The Advanced Time Delayed {beta}{gamma}{gamma}(t) method has been used to measure the half-lives of five levels. The moderately fast B(E1) transition rates derived suggest that the octupole effects, albeit weak, are still present in this exotic nucleus.

  7. Control of Power Converters in AC Microgrids

    DEFF Research Database (Denmark)

    Rocabert, Joan; Luna, Alvaro; Blaabjerg, Frede

    2012-01-01

    The enabling of ac microgrids in distribution networks allows delivering distributed power and providing grid support services during regular operation of the grid, as well as powering isolated islands in case of faults and contingencies, thus increasing the performance and reliability of the ele......The enabling of ac microgrids in distribution networks allows delivering distributed power and providing grid support services during regular operation of the grid, as well as powering isolated islands in case of faults and contingencies, thus increasing the performance and reliability...

  8. Statistical time lags in ac discharges

    International Nuclear Information System (INIS)

    Sobota, A; Kanters, J H M; Van Veldhuizen, E M; Haverlag, M; Manders, F

    2011-01-01

    The paper presents statistical time lags measured for breakdown events in near-atmospheric pressure argon and xenon. Ac voltage at 100, 400 and 800 kHz was used to drive the breakdown processes, and the voltage amplitude slope was varied between 10 and 1280 V ms -1 . The values obtained for the statistical time lags are roughly between 1 and 150 ms. It is shown that the statistical time lags in ac-driven discharges follow the same general trends as the discharges driven by voltage of monotonic slope. In addition, the validity of the Cobine-Easton expression is tested at an alternating voltage form.

  9. Statistical time lags in ac discharges

    Energy Technology Data Exchange (ETDEWEB)

    Sobota, A; Kanters, J H M; Van Veldhuizen, E M; Haverlag, M [Eindhoven University of Technology, Department of Applied Physics, Postbus 513, 5600MB Eindhoven (Netherlands); Manders, F, E-mail: a.sobota@tue.nl [Philips Lighting, LightLabs, Mathildelaan 1, 5600JM Eindhoven (Netherlands)

    2011-04-06

    The paper presents statistical time lags measured for breakdown events in near-atmospheric pressure argon and xenon. Ac voltage at 100, 400 and 800 kHz was used to drive the breakdown processes, and the voltage amplitude slope was varied between 10 and 1280 V ms{sup -1}. The values obtained for the statistical time lags are roughly between 1 and 150 ms. It is shown that the statistical time lags in ac-driven discharges follow the same general trends as the discharges driven by voltage of monotonic slope. In addition, the validity of the Cobine-Easton expression is tested at an alternating voltage form.

  10. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...

  11. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion...

  12. The main directions of pharmacological correction of radioinduced scleroses

    International Nuclear Information System (INIS)

    Dubrovskaya, V.F.

    1991-01-01

    Results of clinical and experimental research on pharmacological correction of radiationinduced sclerosis were summarized. Efficiency of prophylaxis main trends and drug therapy was analyzed. Application of specific pharmaceuticals (preparations directly affecting certain chains of collagen metabolism) and nonspecific pharmaceuticals (preparations of indirect affect on collagen metabolism) was given. Further research of specific pharmaceuticals was shown to be expedient. Analysis of nonspecific pharmaceuticals used in complex therapy revealed problems in evaluating their efficiency at various stages of sclerosis development

  13. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen

    2012-01-01

    Full Text Available Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for 1 in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in central nervous system pathologies is changing from that of magic bullets that target individual chemoreceptors or disease-causing genes into that of magic shotguns, promiscuous or dirty drugs that target disease-causing networks, also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  14. Tinnitus: network pathophysiology-network pharmacology.

    Science.gov (United States)

    Elgoyhen, Ana B; Langguth, Berthold; Vanneste, Sven; De Ridder, Dirk

    2012-01-01

    Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of "magic bullets" that target individual chemoreceptors or "disease-causing genes" into that of "magic shotguns," "promiscuous" or "dirty drugs" that target "disease-causing networks," also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  15. Pharmacology of human experimental anxiety

    Directory of Open Access Journals (Sweden)

    F.G. Graeff

    2003-04-01

    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  16. Carotenoids: biochemistry, pharmacology and treatment.

    Science.gov (United States)

    Milani, Alireza; Basirnejad, Marzieh; Shahbazi, Sepideh; Bolhassani, Azam

    2017-06-01

    Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  17. International Union of Basic and Clinical Pharmacology Review: WNT/Frizzled signalling: receptor–ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3

    Science.gov (United States)

    Dijksterhuis, J P; Petersen, J; Schulte, G

    2014-01-01

    The wingless/int1 (WNT)/Frizzled (FZD) signalling pathway controls numerous cellular processes such as proliferation, differentiation, cell-fate decisions, migration and plays a crucial role during embryonic development. Nineteen mammalian WNTs can bind to 10 FZDs thereby activating different downstream pathways such as WNT/β-catenin, WNT/planar cell polarity and WNT/Ca2+. However, the mechanisms of signalling specification and the involvement of heterotrimeric G proteins are still unclear. Disturbances in the pathways can lead to various diseases ranging from cancer, inflammatory diseases to metabolic and neurological disorders. Due to the presence of seven-transmembrane segments, evidence for coupling between FZDs and G proteins and substantial structural differences in class A, B or C GPCRs, FZDs were grouped separately in the IUPHAR GPCR database as the class FZD within the superfamily of GPCRs. Recently, important progress has been made pointing to a direct activation of G proteins after WNT stimulation. WNT/FZD and G protein coupling remain to be fully explored, although the basic observation supporting the nature of FZDs as GPCRs is compelling. Because the involvement of different (i) WNTs; (ii) FZDs; and (iii) intracellular binding partners could selectively affect signalling specification, in this review we present the current understanding of receptor/ligand selectivity of FZDs and WNTs. We pinpoint what is known about signalling specification and the physiological relevance of these interactions with special emphasis on FZD–G protein interactions. LINKED ARTICLESThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-5 PMID:24032637

  18. Interleukin-13–induced MUC5AC Is Regulated by 15-Lipoxygenase 1 Pathway in Human Bronchial Epithelial Cells

    Science.gov (United States)

    Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B.; O'Donnell, Valerie; Wenzel, Sally E.

    2009-01-01

    Rationale: 15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. Objectives: To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13–induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Methods: Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air–liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Measurements and Main Results: Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Conclusions: Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma. PMID:19218191

  19. Pharmacological therapy for analgesia and sedation in the newborn.

    Science.gov (United States)

    Anand, K J S; Hall, R W

    2006-11-01

    Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non-steroidal anti-inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence-based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long-term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non-pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long-term clinical outcomes.

  20. Holistic Management of Schizophrenia Symptoms Using Pharmacological and Non-pharmacological Treatment.

    Science.gov (United States)

    Ganguly, Pronab; Soliman, Abdrabo; Moustafa, Ahmed A

    2018-01-01

    Individuals with schizophrenia lead a poor quality of life, due to poor medical attention, homelessness, unemployment, financial constraints, lack of education, and poor social skills. Thus, a review of factors associated with the holistic management of schizophrenia is of paramount importance. The objective of this review is to improve the quality of life of individuals with schizophrenia, by addressing the factors related to the needs of the patients and present them in a unified manner. Although medications play a role, other factors that lead to a successful holistic management of schizophrenia include addressing the following: financial management, independent community living, independent living skill, relationship, friendship, entertainment, regular exercise for weight gained due to medication administration, co-morbid health issues, and day-care programmes for independent living. This review discusses the relationship between different symptoms and problems individuals with schizophrenia face (e.g., homelessness and unemployment), and how these can be managed using pharmacological and non-pharmacological methods. Thus, the target of this review is the carers of individuals with schizophrenia, public health managers, counselors, case workers, psychiatrists, and clinical psychologists aiming to enhance the quality of life of individuals with schizophrenia.

  1. Multi-phase AC/AC step-down converter for distribution systems

    Science.gov (United States)

    Aeloiza, Eddy C.; Burgos, Rolando P.

    2017-10-25

    A step-down AC/AC converter for use in an electric distribution system includes at least one chopper circuit for each one of a plurality of phases of the AC power, each chopper circuit including a four-quadrant switch coupled in series between primary and secondary sides of the chopper circuit and a current-bidirectional two-quadrant switch coupled between the secondary side of the chopper circuit and a common node. Each current-bidirectional two-quadrant switch is oriented in the same direction, with respect to the secondary side of the corresponding chopper circuit and the common node. The converter further includes a control circuit configured to pulse-width-modulate control inputs of the switches, to convert a first multiphase AC voltage at the primary sides of the chopper circuits to a second multiphase AC voltage at the secondary sides of the chopper circuits, the second multiphase AC voltage being lower in voltage than the first multiphase AC voltage.

  2. AC loss in superconducting tapes and cables

    NARCIS (Netherlands)

    Oomen, M.P.

    2000-01-01

    The present study discusses the AC loss in high-temperature superconductors. Superconducting materials with a relatively high critical temperature were discovered in 1986. They are presently developed for use in large-scale power-engineering devices such as power-transmission cables, transformers

  3. Composite Based EHV AC Overhead Transmission Lines

    DEFF Research Database (Denmark)

    Sørensen, Thomas Kjærsgaard

    and analysed with regard to the possibilities, limitations and risks widespread application of composite materials on EHV AC overhead transmission lines may present. To form the basis for evaluation of the useability of composite materials, dierent overhead line projects aimed at reducing the environmental...

  4. Ac-dc converter firing error detection

    International Nuclear Information System (INIS)

    Gould, O.L.

    1996-01-01

    Each of the twelve Booster Main Magnet Power Supply modules consist of two three-phase, full-wave rectifier bridges in series to provide a 560 VDC maximum output. The harmonic contents of the twelve-pulse ac-dc converter output are multiples of the 60 Hz ac power input, with a predominant 720 Hz signal greater than 14 dB in magnitude above the closest harmonic components at maximum output. The 720 Hz harmonic is typically greater than 20 dB below the 500 VDC output signal under normal operation. Extracting specific harmonics from the rectifier output signal of a 6, 12, or 24 pulse ac-dc converter allows the detection of SCR firing angle errors or complete misfires. A bandpass filter provides the input signal to a frequency-to-voltage converter. Comparing the output of the frequency-to-voltage converter to a reference voltage level provides an indication of the magnitude of the harmonics in the ac-dc converter output signal

  5. THE ACS NEARBY GALAXY SURVEY TREASURY

    International Nuclear Information System (INIS)

    Dalcanton, Julianne J.; Williams, Benjamin F.; Rosema, Keith; Gogarten, Stephanie M.; Christensen, Charlotte; Gilbert, Karoline; Hodge, Paul; Seth, Anil C.; Dolphin, Andrew; Holtzman, Jon; Skillman, Evan D.; Weisz, Daniel; Cole, Andrew; Girardi, Leo; Karachentsev, Igor D.; Olsen, Knut; Freeman, Ken; Gallart, Carme; Harris, Jason; De Jong, Roelof S.

    2009-01-01

    The ACS Nearby Galaxy Survey Treasury (ANGST) is a systematic survey to establish a legacy of uniform multi-color photometry of resolved stars for a volume-limited sample of nearby galaxies (D 4 in luminosity and star formation rate. The survey data consist of images taken with the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope (HST), supplemented with archival data and new Wide Field Planetary Camera 2 (WFPC2) imaging taken after the failure of ACS. Survey images include wide field tilings covering the full radial extent of each galaxy, and single deep pointings in uncrowded regions of the most massive galaxies in the volume. The new wide field imaging in ANGST reaches median 50% completenesses of m F475W = 28.0 mag, m F606W = 27.3 mag, and m F814W = 27.3 mag, several magnitudes below the tip of the red giant branch (TRGB). The deep fields reach magnitudes sufficient to fully resolve the structure in the red clump. The resulting photometric catalogs are publicly accessible and contain over 34 million photometric measurements of >14 million stars. In this paper we present the details of the sample selection, imaging, data reduction, and the resulting photometric catalogs, along with an analysis of the photometric uncertainties (systematic and random), for both ACS and WFPC2 imaging. We also present uniformly derived relative distances measured from the apparent magnitude of the TRGB.

  6. Predicting AC loss in practical superconductors

    International Nuclear Information System (INIS)

    Goemoery, F; Souc, J; Vojenciak, M; Seiler, E; Klincok, B; Ceballos, J M; Pardo, E; Sanchez, A; Navau, C; Farinon, S; Fabbricatore, P

    2006-01-01

    Recent progress in the development of methods used to predict AC loss in superconducting conductors is summarized. It is underlined that the loss is just one of the electromagnetic characteristics controlled by the time evolution of magnetic field and current distribution inside the conductor. Powerful methods for the simulation of magnetic flux penetration, like Brandt's method and the method of minimal magnetic energy variation, allow us to model the interaction of the conductor with an external magnetic field or a transport current, or with both of them. The case of a coincident action of AC field and AC transport current is of prime importance for practical applications. Numerical simulation methods allow us to expand the prediction range from simplified shapes like a (infinitely high) slab or (infinitely thin) strip to more realistic forms like strips with finite rectangular or elliptic cross-section. Another substantial feature of these methods is that the real composite structure containing an array of superconducting filaments can be taken into account. Also, the case of a ferromagnetic matrix can be considered, with the simulations showing a dramatic impact on the local field. In all these circumstances, it is possible to indicate how the AC loss can be reduced by a proper architecture of the composite. On the other hand, the multifilamentary arrangement brings about a presence of coupling currents and coupling loss. Simulation of this phenomenon requires 3D formulation with corresponding growth of the problem complexity and computation time

  7. Meso Mechanical Analysis of AC Mixture Response

    NARCIS (Netherlands)

    Woldekidan, M.F.; Huurman, M.; Vaccari, E.; Poot, M.

    2012-01-01

    Ongoing research into performance modeling of Asphalt Concrete (AC) mixtures using meso mechanics approaches is being undertaken at Delft University of Technology (TUD). The approach has already been successfully employed for evaluating the long term performance of porous asphalt concrete. The work

  8. 2011 Annual Meeting of the Safety Pharmacology Society: an overview.

    Science.gov (United States)

    Cavero, Icilio

    2012-03-01

    The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

  9. Pharmacologic treatment of depression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus W.; Glazenborg, Arjon; Uyttenboogaart, Maarten; Mostert, Jop; De Keyser, Jacques

    2011-01-01

    Background Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful. Objectives To investigate the efficacy and tolerability of pharmacologic treatments for depression in patients with MS. Search

  10. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond

    2017-01-01

    pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...

  11. Pharmacology of sexually compulsive behavior.

    Science.gov (United States)

    Codispoti, Victoria L

    2008-12-01

    In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction

  12. A review of the medicinal uses, phytochemistry and pharmacology of the genus Sapium.

    Science.gov (United States)

    Al Muqarrabun, L M R; Ahmat, N; Aris, S Ruzaina S

    2014-08-08

    Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several regions such as Malaysia, Africa, Southern China and Bolivia. Most of the species reported to possess therapeutic effects which are used for the treatment of skin-related diseases such as eczema and dermatitis, but they may also be used for overstrain, lumbago, constipation and hernia. Species of this genus are also used to treat wounds and snake bites. In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium sebiferum have/has toxic effects and are used as bird and fish poisons. This review discusses the current knowledge of the medicinal uses, phytochemistry, biological activities and toxicities of species from the genus Sapium to reveal their therapeutic potentials and gaps offering opportunities for future research. This review is based on a literature study of scientific journals and books from libraries and electronic sources, such as ScienceDirect, PubMed and ACS. As many as 65 compounds are included in this review. They belong to different classes of compounds including flavonoids, terpenoids and several other types of compounds, such as alkaloids, phenolic acids and amides. The pharmacological studies revealed that various types of preparations, extracts and single compounds of species from this genus exhibited a broad spectrum of biological activities including antioxidant, antimicrobial, anti-inflammatory and cytotoxic activities. However, Sapium glandulosum, Sapium indicum and Sapium sebiferum were reported to possess toxic effects and Sapium sebiferum was found to contain phorbol esters acting as a tumor-promoting agent. The genus Sapium consists of 23 accepted (high confidence) species. However, only very few of species have been phytochemically and pharmacologically studied. There is great potential to discover new chemical constituents from this genus because only a

  13. Ac, La, and Ce radioimpurities in {sup 225}Ac produced in 40-200 MeV proton irradiations of thorium

    Energy Technology Data Exchange (ETDEWEB)

    Engle, Jonathan W.; Ballard, Beau D. [Los Alamos National Laboratory, NM (United States); Weidner, John W. [Air Force Institute of Technology, Wright Patterson Air Force Base, OH (United States); and others

    2014-10-01

    Accelerator production of {sup 225}Ac addresses the global supply deficiency currently inhibiting clinical trials from establishing {sup 225}Ac's therapeutic utility, provided that the accelerator product is of sufficient radionuclidic purity for patient use. Two proton activation experiments utilizing the stacked foil technique between 40 and 200 MeV were employed to study the likely co-formation of radionuclides expected to be especially challenging to separate from {sup 225}Ac. Foils were assayed by nondestructive γ-spectroscopy and by α-spectroscopy of chemically processed target material. Nuclear formation cross sections for the radionuclides {sup 226}Ac and {sup 227}Ac as well as lower lanthanide radioisotopes {sup 139}Ce, {sup 141}Ce, {sup 143}Ce, and {sup 140}La whose elemental ionic radii closely match that of actinium were measured and are reported. The predictions of the latest MCNP6 event generators are compared with measured data, as they permit estimation of the formation rates of other radionuclides whose decay emissions are not clearly discerned in the complex spectra collected from {sup 232}Th(p,x) fission product mixtures. (orig.)

  14. Problem-based learning in pharmacology:a survey of department heads in Taiwan, China

    Institute of Scientific and Technical Information of China (English)

    Ying-tung LAU

    2004-01-01

    Problem-based learning (PBL) requires active student participation and the use of clinical cases as a trigger to learn within a given area. It has gained much attention as a pedagogic alternative in the course of reform in medica education due to information overload. From discipline-based consideration, it is interesting to understand the views of department heads of pharmacology about implementing PBL for their medical students. According to a general survey from the heads of the department of pharmacology across medical schools in Taiwan, we found that although serious reservation about the approach remains, many departments indeed look forward to including PBL component in their pharmacology curriculum.

  15. α-Mangostin from Garcinia mangostana Linn: An updated review of its pharmacological properties

    Directory of Open Access Journals (Sweden)

    Mohamed Yousif Ibrahim

    2016-05-01

    Full Text Available Over the past decades, various studies have highlighted the pure natural compound, α-mangostin as their main topic. The compound’s pre-clinical and pharmacological properties have been recognized and defined in these studies. α-Mangostin shows strong pharmacological effects in in vitro and in vivo model systems by targeting a number of vital cellular factors through various mechanisms of action. Despite its important molecular versatility, the α-mangostin still has limited clinical application. In order to optimize the conditions of this compound as a chemotherapeutic and chemopreventive agent, for instance in diseases such as cancer, obesity, diabetes as well as inflammatory disorders, the recent tendency is to limit the range of its pharmacological properties. The present work reviews recent studies on the central and potential pharmacological principles as well as the preclinical applications of the α-mangostin.

  16. Assay Methods for ACS Activity and ACS Phosphorylation by MAP Kinases In Vitro and In Vivo.

    Science.gov (United States)

    Han, Xiaomin; Li, Guojing; Zhang, Shuqun

    2017-01-01

    Ethylene, a gaseous phytohormone, has profound effects on plant growth, development, and adaptation to the environment. Ethylene-regulated processes begin with the induction of ethylene biosynthesis. There are two key steps in ethylene biosynthesis. The first is the biosynthesis of 1-aminocyclopropane-1-carboxylic acid (ACC) from S-Adenosyl-Methionine (SAM), a common precursor in many metabolic pathways, which is catalyzed by ACC synthase (ACS). The second is the oxidative cleavage of ACC to form ethylene under the action of ACC oxidase (ACO). ACC biosynthesis is the committing and generally the rate-limiting step in ethylene biosynthesis. As a result, characterizing the cellular ACS activity and understanding its regulation are important. In this chapter, we detail the methods used to measure, (1) the enzymatic activity of both recombinant and native ACS proteins, and (2) the phosphorylation of ACS protein by mitogen-activated protein kinases (MAPKs) in vivo and in vitro.

  17. High voltage AC/AC electrochemical capacitor operating at low temperature in salt aqueous electrolyte

    Science.gov (United States)

    Abbas, Qamar; Béguin, François

    2016-06-01

    We demonstrate that an activated carbon (AC)-based electrochemical capacitor implementing aqueous lithium sulfate electrolyte in 7:3 vol:vol water/methanol mixture can operate down to -40 °C with good electrochemical performance. Three-electrode cell investigations show that the faradaic contributions related with hydrogen chemisorption in the negative AC electrode are thermodynamically unfavored at -40 °C, enabling the system to work as a typical electrical double-layer (EDL) capacitor. After prolonged floating of the AC/AC capacitor at 1.6 V and -40°C, the capacitance, equivalent series resistance and efficiency remain constant, demonstrating the absence of ageing related with side redox reactions at this temperature. Interestingly, when temperature is increased back to 24 °C, the redox behavior due to hydrogen storage reappears and the system behaves as a freshly prepared one.

  18. Digital model for harmonic interactions in AC/DC/AC systems

    Energy Technology Data Exchange (ETDEWEB)

    Guarini, A P; Rangel, R D; Pilotto, L A.S.; Pinto, R J; Passos, Junior, R [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil)

    1994-12-31

    The main purpose of this paper is to present a model for calculation of HVdc converter harmonics taking into account the influence of the harmonic interactions between the ac systems in dc link transmissions. The ideas and methodologies used in the model development take into account the dc current ripple and ac voltage distortion in the ac systems. The theory of switching functions is applied to contemplate for the frequency conversions between the ac and dc sides, in an iterative process. It is possible then to obtain, even in balanced situations, non-characteristic harmonics that are produced by frequencies originated in the other terminal, which can be significant in a strongly coupled system, such as back-to-back configuration. (author) 9 refs., 3 figs.

  19. Cardiovascular Safety Pharmacology of Sibutramine.

    Science.gov (United States)

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

    2015-07-01

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

  20. [Pharmacologic treatment of osteoporosis--2011].

    Science.gov (United States)

    Lakatos, Péter

    2011-08-14

    Osteoporosis affects approximately 9% of the population in Hungary resulting in about 100 000 osteoporotic fractures annually. Thirty-five percent of patients with hip fractures due to osteoporosis will die within 1 year. Direct costs of osteoporosis exceed 25 billion forints per year. Apparently, cost-effective reduction of bone loss and consequent fracture risk will add up to not only financial savings but improvement in quality of life, as well. A number of pharmacological modalities are available for this purpose. The mainstay of the treatment of osteoporosis is the bisphosphonate group that includes effective anti-resorptive compounds mitigating bone loss and fragility. The recently registered denosumab exhibits similar efficacy by neutralizing RANK ligand, however, marked differences can be observed between the two drug classes. Strontium has a unique mechanism of action by rebalancing bone turnover, and thus, providing an efficient treatment option for the not fast bone losers who are at high fracture risk. The purely anabolic teriparatide is available for the extremely severe osteoporotic patients and for those who do not respond to other types of therapy. Older treatment options such as hormone replacement therapy, raloxifene, tibolone or calcitonin may also have a restricted place in the management of osteoporosis.

  1. Pharmacological Fingerprints of Contextual Uncertainty.

    Directory of Open Access Journals (Sweden)

    Louise Marshall

    2016-11-01

    Full Text Available Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.

  2. Approaches to building single-stage AC/AC conversion switch-mode audio power amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.; Andersen, Michael A.E.

    2005-07-01

    This paper discusses the possible topologies and promising approaches towards direct single-phase AC-AC conversion of the mains voltage for audio applications. When compared to standard Class-D switching audio power amplifiers with a separate power supply, it is expected that direct conversion will provide better efficiency and higher level of integration, leading to lower component count, volume and cost, but at the expense of a minor performance deterioration. (au)

  3. Pharmacological approach of the receptors

    International Nuclear Information System (INIS)

    Puech, A.J.

    1989-01-01

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

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

    Science.gov (United States)

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

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

  5. Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics

    Science.gov (United States)

    Kazdoba, Tatiana M.; Leach, Prescott T.; Yang, Mu; Silverman, Jill L.; Solomon, Marjorie

    2016-01-01

    Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism. PMID:27305922

  6. Phytochemical and pharmacological properties of essential oils from Cedrus species.

    Science.gov (United States)

    Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

    2018-06-01

    Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

  7. Faradaic AC Electrokinetic Flow and Particle Traps

    Science.gov (United States)

    Ben, Yuxing; Chang, Hsueh-Chia

    2004-11-01

    Faradaic reaction at higher voltages can produce co-ion polarization at AC electrodes instead of counter-ion polarization due to capacitive charging from the bulk. The Faradaic co-ion polarization also does not screen the external field and hence can produce large net electro-kinetic flows at frequencies lower than the inverse RC time of the double layer. Due to the opposite polarization of capacitve and Faradaic charging, we can reverse the direction of AC flows on electrodes by changing the voltage and frequency. Particles and bacteria are trapped and then dispersed at stagnation lines, at locations predicted by our theory, by using these two flows sequentially. This technique offers a good way to concentrate and detect bacteria.

  8. AC application of second generation HTS wire

    Science.gov (United States)

    Thieme, C. L. H.; Gagnon, K.; Voccio, J.; Aized, D.; Claassen, J.

    2008-02-01

    For the production of Second Generation (2G) YBCO High Temperature Superconductor wire American Superconductor uses a wide-strip MOD-YBCO/RABiTSTM process, a low-cost approach for commercial manufacturing. It can be engineered with a high degree of flexibility to manufacture practical 2G conductors with architectures and properties tailored for specific applications and operating conditions. For ac applications conductor and coil design can be geared towards low hysteretic losses. For applications which experience high frequency ac fields, the stabilizer needs to be adjusted for low eddy current losses. For these applications a stainless-steel laminate is used. An example is a Low Pass Filter Inductor which was developed and built in this work.

  9. Aging, Counterfeiting Configuration Control (AC3)

    Science.gov (United States)

    2010-01-31

    Systems Intergrated Into AC3 CABS - Common As-Built System PRISM - Process Re-inventing Integration Systems for Manufacturing PDM - Product Data...looks forward to deploying the completed tool at Raytheon in a true production environment, for as much as we like the challenge associated with...performance of DoD systems. DoD systems are particularly susceptible to intrusion of counterfeit parts, especially during surge and extended production

  10. The LHC AC Dipole system: an introduction

    CERN Document Server

    Serrano, J; CERN. Geneva. BE Department

    2010-01-01

    The LHC AC Dipole is an instrument to study properties of the LHC lattice by inducing large transverse displacements in the beam. These displacements are generated by exciting the beam with an oscillating magnetic field at a frequency close to the tune. This paper presents the system requirements and the technical solution chosen to meet them, based of high-power audio amplifiers and a resonant parallel RLC circuit.

  11. Modeling photovoltaic systems for AC appliances

    Directory of Open Access Journals (Sweden)

    Andreea Maria Neaca

    2009-10-01

    Full Text Available In this paper is described the development of a model which can simulate the performance of a photovoltaic (PV system under specific meteorological conditions and transforming the DC current into AC current. In this model, the accent stands on the design of a series charge regulator. It is treated also the benefit of creating a circuit, with different methods, that can test the maximum power point trackers (MPPT for different photovoltaic applications.

  12. Control of grid interactive AC microgrids

    DEFF Research Database (Denmark)

    Wang, Xiongfei; Guerrero, Josep M.; Chen, Zhe

    2010-01-01

    Over the last decade, distributed energy resources (DER) technology has undergone a fast development. Increased penetration of DER units and wide spread use of renewable energy sources challenge the entire architecture of traditional power system. Microgrid, characterizing higher flexibility......, microgrid controls and power management strategies are presented. Future trends of microgrid are discussed pointing out how this concept can be a key to achieve a more intelligent and flexible AC grid....

  13. CTE Corrections for WFPC2 and ACS

    Science.gov (United States)

    Dolphin, Andrew

    2003-07-01

    The error budget for optical broadband photometry is dominated by three factors: CTE corrections, long-short anomaly corrections, and photometric zero points. Questions about the dependencies of the CTE have largely been resolved, and my CTE corrections have been included in the WFPC2 handbook and tutorial. What remains to be done is the determination of the "final" CTE correction at the end of the WFPC2 mission, which will increase the accuracy of photometry obtained in the final few cycles. The long-short anomaly is still the subject of much debate, as it remains unclear whethere or not this effect is real and, if so, what its size and nature is. Photometric zero points have likewise varied by over 0.05 magnitudes in the literature, and will likely remain unresolved until the long-short anomaly is addressed {given that most calibration exposures are short while most science exposures are long}. It is also becoming apparent that similar issues will affect the accuracy of ACS photometry, and consequently that an ACS CTE study analogous to my WFPC2 work would significantly improve the calibration of ACS. I therefore propose to use archival WFPC2 images of omega Cen and ACS images of 47 Tuc to continue my HST calibration work. I also propose to begin work on "next-generation" CTE corrections, in which corrections are applied to the images based on accurate charge-trapping models rather than to the reduced photometry. This technique will allow for more accurate CTE corrections in certain cases {such as a star above a bright star or on a variable background}, improved PSF-fitting photometry of faint stars, and image restoration for accurate analysis of extended objects.

  14. Review of the Chemistry and Pharmacology of 7-Methyljugulone ...

    African Journals Online (AJOL)

    Review of the Chemistry and Pharmacology of 7-Methyljugulone. ... Methods: The chemical and pharmacological data were retrieved from the well-known scientific websites such as Pubmed, Google Scholar, Reaxys, Scirus, Scopus, ... Keywords: 7-methyljugulone; biosynthesis; in vitro synthesis; pharmacology

  15. AcT-2: a novel myotropic and antimicrobial type 2 tryptophyllin from the skin secretion of the Central American red-eyed leaf frog, Agalychnis callidryas.

    Science.gov (United States)

    Ge, Lilin; Lyu, Peng; Zhou, Mei; Zhang, Huiling; Wan, Yuantai; Li, Bin; Li, Renjie; Wang, Lei; Chen, Tianbao; Shaw, Chris

    2014-01-01

    Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure--GMRPPWF-NH2--was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μ M). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

  16. AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog, Agalychnis callidryas

    Directory of Open Access Journals (Sweden)

    Lilin Ge

    2014-01-01

    Full Text Available Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μM. The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L Escherichia coli (MIC = 512 mg/L, and Candida albicans (128 mg/L. AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

  17. [PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

    Science.gov (United States)

    Bondarchuk, N G; Fisenko, V P

    2016-01-01

    Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

  18. Problems of pharmacological supply of disaster medicine

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  19. [Contribution of animal experimentation to pharmacology].

    Science.gov (United States)

    Sassard, Jean; Hamon, Michel; Galibert, Francis

    2009-11-01

    Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

  20. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    Science.gov (United States)

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  1. Direct amplitude detuning measurement with ac dipole

    Directory of Open Access Journals (Sweden)

    S. White

    2013-07-01

    Full Text Available In circular machines, nonlinear dynamics can impact parameters such as beam lifetime and could result in limitations on the performance reach of the accelerator. Assessing and understanding these effects in experiments is essential to confirm the accuracy of the magnetic model and improve the machine performance. A direct measurement of the machine nonlinearities can be obtained by characterizing the dependency of the tune as a function of the amplitude of oscillations (usually defined as amplitude detuning. The conventional technique is to excite the beam to large amplitudes with a single kick and derive the tune from turn-by-turn data acquired with beam position monitors. Although this provides a very precise tune measurement it has the significant disadvantage of being destructive. An alternative, nondestructive way of exciting large amplitude oscillations is to use an ac dipole. The perturbation Hamiltonian in the presence of an ac dipole excitation shows a distinct behavior compared to the free oscillations which should be correctly taken into account in the interpretation of experimental data. The use of an ac dipole for direct amplitude detuning measurement requires careful data processing allowing one to observe the natural tune of the machine; the feasibility of such a measurement is demonstrated using experimental data from the Large Hadron Collider. An experimental proof of the theoretical derivations based on measurements performed at injection energy is provided as well as an application of this technique at top energy using a large number of excitations on the same beam.

  2. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Science.gov (United States)

    Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

    2016-01-01

    The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

  3. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Directory of Open Access Journals (Sweden)

    Pirow Bekker

    Full Text Available The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan, an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

  4. Pharmacological characterization of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor

    International Nuclear Information System (INIS)

    Orr, G.L.; Gole, J.W.D.; Notman, H.J.; Downer, R.G.H.

    1987-01-01

    Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 μM and 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 μM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 μM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D 2 -dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 μM. Other dopamine agonists have no stimulatory effects. With the exception of mianserin, 3 H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D 1 - and D 2 -dopamine receptors. 33 references, 3 figures, 2 tables

  5. Flame spread over inclined electrical wires with AC electric fields

    KAUST Repository

    Lim, Seung J.; Park, Sun H.; Park, Jeong; Fujita, Osamu; Keel, Sang I.; Chung, Suk-Ho

    2017-01-01

    Flame spread over polyethylene-insulated electrical wires was studied experimentally with applied alternating current (AC) by varying the inclination angle (θ), applied voltage (VAC), and frequency (fAC). For the baseline case with no electric field

  6. The Hubble Legacy Archive ACS grism data

    Science.gov (United States)

    Kümmel, M.; Rosati, P.; Fosbury, R.; Haase, J.; Hook, R. N.; Kuntschner, H.; Lombardi, M.; Micol, A.; Nilsson, K. K.; Stoehr, F.; Walsh, J. R.

    2011-06-01

    A public release of slitless spectra, obtained with ACS/WFC and the G800L grism, is presented. Spectra were automatically extracted in a uniform way from 153 archival fields (or "associations") distributed across the two Galactic caps, covering all observations to 2008. The ACS G800L grism provides a wavelength range of 0.55-1.00 μm, with a dispersion of 40 Å/pixel and a resolution of ~80 Å for point-like sources. The ACS G800L images and matched direct images were reduced with an automatic pipeline that handles all steps from archive retrieval, alignment and astrometric calibration, direct image combination, catalogue generation, spectral extraction and collection of metadata. The large number of extracted spectra (73,581) demanded automatic methods for quality control and an automated classification algorithm was trained on the visual inspection of several thousand spectra. The final sample of quality controlled spectra includes 47 919 datasets (65% of the total number of extracted spectra) for 32 149 unique objects, with a median iAB-band magnitude of 23.7, reaching 26.5 AB for the faintest objects. Each released dataset contains science-ready 1D and 2D spectra, as well as multi-band image cutouts of corresponding sources and a useful preview page summarising the direct and slitless data, astrometric and photometric parameters. This release is part of the continuing effort to enhance the content of the Hubble Legacy Archive (HLA) with highly processed data products which significantly facilitate the scientific exploitation of the Hubble data. In order to characterize the slitless spectra, emission-line flux and equivalent width sensitivity of the ACS data were compared with public ground-based spectra in the GOODS-South field. An example list of emission line galaxies with two or more identified lines is also included, covering the redshift range 0.2 - 4.6. Almost all redshift determinations outside of the GOODS fields are new. The scope of science projects

  7. Alpha decay 225 Ac → 221Fr

    International Nuclear Information System (INIS)

    Gromov, K. Ya.; Gorozhankin, V.M.; Malov, L.A.; Fominykh, V.I.; Tsupko-Sitnikov, V.V.; Chumin, V.G.; Jakushev, E.A.; Kudrya, S.A.; Sergienko, V.A.; Malikov, Sh.R.

    2004-01-01

    Full text: Considerable attention has been given to nuclei with A = 220 - 230 recently. In this region there occurs transition from the spherical to the deformed nuclear shape, which gives rise to some specific features in the nuclear structure. In particular, negative parity levels with low excitation energies have been found in even-even nuclei from this region [1, 2]. One of the nuclei allowing experimental investigation of the above properties is 221 Fr. The nuclide 221 Fr is from the region of isotopes which does not include stable nuclei and thus it cannot be studied in several-nucleon transfer reactions. In addition, the neutron excess in this nucleus makes it impossible to study the nucleus in reactions with heavy ions. Experimental information on the 221 Fr level structure can only be gained from investigation of the 225 Ac (T 1/2 = 10 days) alpha decay or the 221 Rn (T 1/2 = 25 min) beta decay. In the latter case the possibilities of the investigation are restricted by difficulties in making of 221 Rn sources. Therefore, most information on the structure and properties of 221 Fr is derived from investigation of the 225 Ac α -decay [3]. In-depth investigation of ( α - γ )- coincidences at the 225 Ac decay is carried out. Twenty-one new weak γ - rays are found; 18 γ-rays earlier ascribed to the 225 Ac decay are not confirmed. The quantitative analysis of the ( α - γ )- coincidences makes it possible to find the intensity of 221 Fr levels by the decay and multipolarities of five weak γ -transitions. The conversion electron spectrum is investigated in the range of 5 † 24 keV with a high (some 20 eV) energy resolution. A new M1 type 10.6-keV γ-transition is found. The proposed 225 Ac decay scheme includes 31 excited 221 Fr states. Parities are established for 16 of them. Possible spin values are proposed for 221 Fr levels. Properties of excited 221 Fr states are satisfactorily described by the quasiparticle-phonon nuclear model without the

  8. Pharmacology education in North American dental schools: the basic science survey series.

    Science.gov (United States)

    Gautam, Medha; Shaw, David H; Pate, Ted D; Lambert, H Wayne

    2013-08-01

    As part of the Basic Science Survey Series (BSSS) for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed course directors of basic pharmacology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-nine of sixty-seven (73.1 percent) U.S. and Canadian dental schools. The findings suggest the following: 1) substantial variation exists in instructional hours, faculty affiliation, placement within curriculum, class size, and interdisciplinary nature of pharmacology courses; 2) pharmacology course content emphasis is similar among schools; 3) the number of contact hours in pharmacology has remained stable over the past three decades; 4) recent curricular changes were often directed towards enhancing the integrative and clinically relevant aspects of pharmacology instruction; and 5) a trend toward innovative content delivery, such as use of computer-assisted instruction applications, is evident. Data, derived from this study, may be useful to pharmacology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.

  9. Tratamento farmacológico do transtorno bipolar: as evidências de ensaios clínicos randomizados Pharmacological treatment of bipolar disorder: evidence from randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Flávio Kapczinski

    2005-01-01

    Full Text Available O presente artigo é uma síntese das evidências provenientes de ensaios clínicos randomizados sobre o tratamento do transtorno bipolar. A metodologia para a busca do material disponível é descrita, e os resultados são apresentados. Com o melhor nível de evidência disponível, ou seja, revisões sistemáticas de mais de um ensaio clínico randomizado ou pelo menos um ensaio clínico randomizado, temos as seguintes recomendações: 1 a mania aguda pode ser tratada com Lítio, Valproato, Carbamazepina, e antipsicóticos; 2 a depressão bipolar pode ser tratada com antidepressivos (com risco aumentado de virada para mania, com lamotrigina e a associação fluoxetina/olanzapina e 3 a manutenção do transtorno bipolar pode ser realizada com o lítio, valproato, carbamazepina, olanzapina e lamotrigina (quando o objetivo for a profilaxia da depressão bipolar. A não existência de ensaios clínicos publicados não significa que determinadas intervenções não sejam úteis.The present article is a synthesis of the published clinical trials about the treatment of Bipolar disorder (BD. The methodology used to search the literature is described and results are presented. Using the best available evidence (systematic reviews of clinical trials or at lest one randomized clinical trial the following is recommended: 1 acute mania can be treated with lithium, carbamazepine, valrpoate and antipsychotics; 2 acute depression can be treated with lamotrigine, olanzapine/fluoxetine combination and with antidepressants (with an increased risk of switch into mania; 3 maintenance can be performed using lithium, valproate, olanzapine and lamotrigine (when the aim is prophylaxis of bipolar depression. The absence of published results about certain interventions does not mean that such interventions are not useful.

  10. Phytochemical and pharmacological overview on Liriopes radix

    African Journals Online (AJOL)

    Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee. University ... has been used as a therapeutic drug for the treatment of ..... Alzheimer's disease (AD) is characterized by.

  11. Ethnobotanical, phytochemical and pharmacological properties of ...

    African Journals Online (AJOL)

    Electronic search engines such as Google, Google scholar, publishing sites such as Elsevier .... A number of pharmacological activities of C. bulbispermum have been ..... bulbispermum using the direct plate method and minimum inhibitory ...

  12. Medicinal, Pharmacological and Phytochemical Potentials of ...

    African Journals Online (AJOL)

    Medicinal, Pharmacological and Phytochemical Potentials of Annona Comosus linn. ... Therapeutic plants, and the drugs derived from them, are the most important ... also as treatment to: diarrhea, indigestion, pneumonia, bronchitis, arthritis, ...

  13. Disrupting reconsolidation: pharmacological and behavioral manipulations

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2011-01-01

    We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited

  14. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    2014-01-27

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

  15. ORIGINAL ARTICLES Pharmacological testing in Horner's syndrome

    African Journals Online (AJOL)

    topical cocaine 10% in both eyes gave an odds ratio of 1 050:1 that. Horner's syndrome ... nerve endings and therefore do not stimulate the effector cells directly. ... Pharmacological testing in Horner's syndrome – a new paradigm. Derrick P ...

  16. The impact of comorbid post-traumatic stress disorder in patients with major depressive disorder on clinical features, pharmacological treatment strategies, and treatment outcomes - Results from a cross-sectional European multicenter study.

    Science.gov (United States)

    Dold, Markus; Bartova, Lucie; Kautzky, Alexander; Souery, Daniel; Mendlewicz, Julien; Serretti, Alessandro; Porcelli, Stefano; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

    2017-07-01

    This international, multicenter, cross-sectional study comprising 1346 adult in- and outpatients with major depressive disorder (MDD) investigated the association between MDD as primary diagnosis and comorbid post-traumatic stress disorder (PTSD). In a cross-sectional data collection process, the presence of comorbid PTSD was determined by the Mini International Neuropsychiatric Interview (MINI) and the patients' socio-demographic, clinical, psychopharmacological, and response information were obtained. Clinical features between MDD with and without concurrent PTSD were compared using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. 1.49% of the MDD patients suffered from comorbid PTSD. Significantly more MDD + comorbid PTSD patients exhibited atypical features, comorbid anxiety disorders (any comorbid anxiety disorder, panic disorder, agoraphobia, and social phobia), comorbid bulimia nervosa, current suicide risk, and augmentation treatment with low-dose antipsychotic drugs. In the binary logistic regression analyses, the presence of atypical features (odds ratio (OR) = 4.49, 95%CI:1.01-20.12; p≤.05), any comorbid anxiety disorder (OR = 3.89, 95%CI:1.60-9.44; p = .003), comorbid panic disorder (OR = 6.45, 95%CI:2.52-16.51; p = .001), comorbid agoraphobia (OR = 6.51, 95%CI:2.54-16.68; p≤.001), comorbid social phobia (OR = 6.16, 95%CI:1.71-22.17; p≤.001), comorbid bulimia nervosa (OR = 10.39, 95%CI:1.21-88.64; p = .03), current suicide risk (OR = 3.58, 95%CI:1.30-9.91; p = .01), and augmentation with low-potency antipsychotics (OR = 6.66, 95%CI:2.50-17.77; pdisorders, and (3.) the increased suicide risk due to concurrent PTSD. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  17. Importance of Attenuation Correction (AC) for Small Animal PET Imaging

    DEFF Research Database (Denmark)

    El Ali, Henrik H.; Bodholdt, Rasmus Poul; Jørgensen, Jesper Tranekjær

    2012-01-01

    was performed. Methods: Ten NMRI nude mice with subcutaneous implantation of human breast cancer cells (MCF-7) were scanned consecutively in small animal PET and CT scanners (MicroPETTM Focus 120 and ImTek’s MicroCATTM II). CT-based AC, PET-based AC and uniform AC methods were compared. Results: The activity...

  18. Pharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis.

    Science.gov (United States)

    Miller, Elzbieta; Morel, Agnieszka; Redlicka, Justyna; Miller, Igor; Saluk, Joanna

    2018-01-01

    Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to 65 percent of MS patients have cognitive deficits such as episodic memory, sustained attention, reduced verbal fluency; however, the cognitive MS domain is information processing speed. It is the first syndrome of cognitive dysfunction and the most widely affected in MS. Occasionally these impairments occur even before the appearance of physical symptoms. Therefore, this review focused on the current status of our knowledge about possible methods of treatment cognitive impairment in MS patients including novel strategies. Research and online content was performed using Medline and EMBASE databases. The most recent research suggests that cognitive impairment is correlated with brain lesion volume and brain atrophy. The examination of the cognitive impairment is usually based on particular neuropsychological batteries. However, it can be not enough to make a precise diagnosis. This creates a demand to find markers that might be useful for identifying patients with risk of cognitive impairment at an early stage of the disease. Currently the most promising methods consist of neuroimaging indicators, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Diagnosis problems are strictly connected with treatment procedures. There are two main cognitive therapies: pharmacological (disease modifying drugs (DMD), symptomatic treatments) and non-pharmacological interventions that are focused on psychological and physical rehabilitation. Some trials have shown a positive association between physical activity and the cognitive function. This article is an overview of the current state of knowledge related to cognition impairment treatment in MS. Additionally, novel strategies for cognitive impairments such as cryostimulation and other complementary methods are

  19. Precision pharmacology for Alzheimer's disease.

    Science.gov (United States)

    Hampel, Harald; Vergallo, Andrea; Aguilar, Lisi Flores; Benda, Norbert; Broich, Karl; Cuello, A Claudio; Cummings, Jeffrey; Dubois, Bruno; Federoff, Howard J; Fiandaca, Massimo; Genthon, Remy; Haberkamp, Marion; Karran, Eric; Mapstone, Mark; Perry, George; Schneider, Lon S; Welikovitch, Lindsay A; Woodcock, Janet; Baldacci, Filippo; Lista, Simone

    2018-04-01

    The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses. Consequently, the distinct pattern of AD pathophysiology in space and time must be investigated on the basis of the individual biological makeup. This requires the implementation of systems biology and neurophysiology to facilitate Precision Medicine (PM) and Precision Pharmacology (PP). The regulation of several processes at multiple levels of complexity from gene expression to cellular cycle to tissue repair and system-wide network activation has different time delays (temporal scale) according to the affected systems (spatial scale). The initial failure might originate and occur at every level potentially affecting the whole dynamic interrelated systems within an organism. Unraveling the spatial and temporal dynamics of non-linear pathophysiological mechanisms across the continuum of hierarchical self-organized systems levels and from systems homeostasis to systems failure is key to understand AD. Measuring and, possibly, controlling space- and time-scaled adaptive and compensatory responses occurring during AD will represent a crucial step to achieve the capacity to substantially modify the disease course and progression at the best suitable timepoints, thus counteracting disrupting critical pathophysiological inputs. This approach will provide the conceptual basis for effective

  20. Punishment, Pharmacological Treatment, and Early Release

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2013-01-01

    Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....

  1. Development of a hardware-based AC microgrid for AC stability assessment

    Science.gov (United States)

    Swanson, Robert R.

    As more power electronic-based devices enable the development of high-bandwidth AC microgrids, the topic of microgrid power distribution stability has become of increased interest. Recently, researchers have proposed a relatively straightforward method to assess the stability of AC systems based upon the time-constants of sources, the net bus capacitance, and the rate limits of sources. In this research, a focus has been to develop a hardware test system to evaluate AC system stability. As a first step, a time domain model of a two converter microgrid was established in which a three phase inverter acts as a power source and an active rectifier serves as an adjustable constant power AC load. The constant power load can be utilized to create rapid power flow transients to the generating system. As a second step, the inverter and active rectifier were designed using a Smart Power Module IGBT for switching and an embedded microcontroller as a processor for algorithm implementation. The inverter and active rectifier were designed to operate simultaneously using a synchronization signal to ensure each respective local controller operates in a common reference frame. Finally, the physical system was created and initial testing performed to validate the hardware functionality as a variable amplitude and variable frequency AC system.

  2. Pixel-based CTE Correction of ACS/WFC: Modifications To The ACS Calibration Pipeline (CALACS)

    Science.gov (United States)

    Smith, Linda J.; Anderson, J.; Armstrong, A.; Avila, R.; Bedin, L.; Chiaberge, M.; Davis, M.; Ferguson, B.; Fruchter, A.; Golimowski, D.; Grogin, N.; Hack, W.; Lim, P. L.; Lucas, R.; Maybhate, A.; McMaster, M.; Ogaz, S.; Suchkov, A.; Ubeda, L.

    2012-01-01

    The Advanced Camera for Surveys (ACS) was installed on the Hubble Space Telescope (HST) nearly ten years ago. Over the last decade, continuous exposure to the harsh radiation environment has degraded the charge transfer efficiency (CTE) of the CCDs. The worsening CTE impacts the science that can be obtained by altering the photometric, astrometric and morphological characteristics of sources, particularly those farthest from the readout amplifiers. To ameliorate these effects, Anderson & Bedin (2010, PASP, 122, 1035) developed a pixel-based empirical approach to correcting ACS data by characterizing the CTE profiles of trails behind warm pixels in dark exposures. The success of this technique means that it is now possible to correct full-frame ACS/WFC images for CTE degradation in the standard data calibration and reduction pipeline CALACS. Over the past year, the ACS team at STScI has developed, refined and tested the new software. The details of this work are described in separate posters. The new code is more effective at low flux levels (repair ACS electronics) and pixel-based CTE correction. In addition to the standard cosmic ray corrected, flat-fielded and drizzled data products (crj, flt and drz files) there are three new equivalent files (crc, flc and drc) which contain the CTE-corrected data products. The user community will be able to choose whether to use the standard or CTE-corrected products.

  3. Preemptive analgesia I: physiological pathways and pharmacological modalities.

    LENUS (Irish Health Repository)

    Kelly, D J

    2012-02-03

    PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

  4. Pharmacological treatment of chronic constipation: a literature review

    Directory of Open Access Journals (Sweden)

    Roshanak Salari

    2016-07-01

    Full Text Available Chronic constipation is a very common disease that is particularly commonplace among members of the elderly population. It is one of the most widespread bowel disorders, and it causes significant pain and discomfort; as such, it usually requires medical attention. The major causes of constipation are slow colonic movements and/or functional gastrointestinal disorders. This review aimed to examine the pharmacological treatments that are currently available for chronic constipation. To develop insights into the causes and treatments of chronic constipation, relevant review articles that were published on the Pubmed, Cochrane database, and Embase websites, were examined. The outputs of these studies indicated that high daily intake of fibers and fluids in addition to regular exercise can be very helpful in avoiding and treating constipation. The pharmacological treatments that are administered to treat this disease typically increase the water content of the bowel lumen, and this leads to more regular bowel movements. Novel drugs have been introduced to treat constipation, and many of these are now subject to formal research studies. Since constipation can facilitate the development of other gastrointestinal diseases, it is important that we develop an understanding the therapeutic treatments that are available with the intention of identifying which of these may represent the most effective method for treating this disease. With that objective in mind, this review was undertaken to review the clinical effectiveness of the different pharmacological treatments that are employed to treat or prevent constipation.

  5. Taiwan consensus of pharmacological treatment for bipolar disorder

    Directory of Open Access Journals (Sweden)

    Ya-Mei Bai

    2013-10-01

    Full Text Available Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN – the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP. The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts’ experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.

  6. How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

    Science.gov (United States)

    Yuan, Haidan; Ma, Qianqian; Cui, Heying; Liu, Guancheng; Zhao, Xiaoyan; Li, Wei; Piao, Guangchun

    2017-07-07

    Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.

  7. Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Hashmi

    2015-01-01

    Full Text Available Aim of the Review. To grasp the fragmented information available on the botany, traditional uses, phytochemistry, pharmacology, and toxicology of Olea europaea to explore its therapeutic potential and future research opportunities. Material and Methods. All the available information on O. europaea was collected via electronic search (using Pubmed, Scirus, Google Scholar, and Web of Science and a library search. Results. Ethnomedical uses of O. europaea are recorded throughout the world where it has been used to treat various ailments. Phytochemical research had led to the isolation of flavonoids, secoiridoids, iridoids, flavanones, biophenols, triterpenes, benzoic acid derivatives, isochromans, and other classes of secondary metabolites from O. europaea. The plant materials and isolated components have shown a wide spectrum of in vitro and in vivo pharmacological activities like antidiabetic, anticonvulsant, antioxidant, anti-inflammatory, immunomodulatory, analgesic, antimicrobial, antiviral, antihypertensive, anticancer, antihyperglycemic, antinociceptive, gastroprotective, and wound healing activities. Conclusions. O. europaea emerged as a good source of traditional medicine for the treatment of various ailments. The outcomes of phytochemical and pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincing support to its future clinical use in modern medicine.

  8. Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive)

    Science.gov (United States)

    Hashmi, Muhammad Ali; Khan, Afsar; Hanif, Muhammad; Farooq, Umar; Perveen, Shagufta

    2015-01-01

    Aim of the Review. To grasp the fragmented information available on the botany, traditional uses, phytochemistry, pharmacology, and toxicology of Olea europaea to explore its therapeutic potential and future research opportunities. Material and Methods. All the available information on O. europaea was collected via electronic search (using Pubmed, Scirus, Google Scholar, and Web of Science) and a library search. Results. Ethnomedical uses of O. europaea are recorded throughout the world where it has been used to treat various ailments. Phytochemical research had led to the isolation of flavonoids, secoiridoids, iridoids, flavanones, biophenols, triterpenes, benzoic acid derivatives, isochromans, and other classes of secondary metabolites from O. europaea. The plant materials and isolated components have shown a wide spectrum of in vitro and in vivo pharmacological activities like antidiabetic, anticonvulsant, antioxidant, anti-inflammatory, immunomodulatory, analgesic, antimicrobial, antiviral, antihypertensive, anticancer, antihyperglycemic, antinociceptive, gastroprotective, and wound healing activities. Conclusions. O. europaea emerged as a good source of traditional medicine for the treatment of various ailments. The outcomes of phytochemical and pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincing support to its future clinical use in modern medicine. PMID:25802541

  9. The pharmacology of neurokinin receptors in addiction: prospects for therapy

    Directory of Open Access Journals (Sweden)

    Sandweiss AJ

    2015-09-01

    Full Text Available Alexander J Sandweiss, Todd W VanderahDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USAAbstract: Addiction is a chronic disorder in which consumption of a substance or a habitual behavior becomes compulsive and often recurrent, despite adverse consequences. Substance p (SP is an undecapeptide and was the first neuropeptide of the neurokinin family to be discovered. The subsequent decades of research after its discovery implicated SP and its neurokinin relatives as neurotransmitters involved in the modulation of the reward pathway. Here, we review the neurokinin literature, giving a brief historical perspective of neurokinin pharmacology, localization in various brain regions involved in addictive behaviors, and the functional aspects of neurokinin pharmacology in relation to reward in preclinical models of addiction that have shaped the rational drug design of neurokinin antagonists that could translate into human research. Finally, we will cover the clinical investigations using neurokinin antagonists and discuss their potential as a therapy for drug abuse.Keywords: reward, substance p, alcohol, morphine, cocaine, dopamine

  10. CliniCal

    African Journals Online (AJOL)

    2009-12-01

    Dec 1, 2009 ... tion choices, available data from clinical studies and expert paediatric pharmacology ... large volumes required or palatability, solid dosage formulations are ... crushed and added to food or liquid, it is important that the entire ...

  11. A comparison of medical and pharmacy students' knowledge and skills of pharmacology and pharmacotherapy.

    Science.gov (United States)

    Keijsers, Carolina J P W; Brouwers, Jacobus R B J; de Wildt, Dick J; Custers, Eugene J F M; Ten Cate, Olle Th J; Hazen, Ankie C M; Jansen, Paul A F

    2014-10-01

    Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical students after their undergraduate training. Differences could serve as a starting point from which to develop joint interdisciplinary educational programmes for better prescribing. In a cross-sectional design, the knowledge and skills of advanced pharmacy and medical students were assessed, using a standardized test with three domains (basic pharmacology knowledge, clinical or applied pharmacology knowledge and pharmacotherapy skills) and eight subdomains (pharmacodynamics, pharmacokinetics, interactions and side-effects, Anatomical Therapeutic Chemical Classification groups, prescribing, prescribing for special groups, drug information, regulations and laws, prescription writing). Four hundred and fifty-one medical and 151 pharmacy students were included between August 2010 and July 2012. The response rate was 81%. Pharmacy students had better knowledge of basic pharmacology than medical students (77.0% vs. 68.2% correct answers; P students had better skills than pharmacy students in writing prescriptions (68.6% vs. 50.7%; P students had similar knowledge of applied pharmacology (73.8% vs. 72.2%, P = 0.124, δ = 0.15). Pharmacy students have better knowledge of basic pharmacology, but not of the application of pharmacology knowledge, than medical students, whereas medical students are better at writing prescriptions. Professional differences in knowledge and skills therefore might well stem from their undergraduate education. Knowledge of these differences could be harnessed to develop a joint interdisciplinary education for both students and professionals. © 2014 The British Pharmacological Society.

  12. Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study.

    Science.gov (United States)

    Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

    2018-06-01

    To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  13. An overview on Phyllanthus emblica: phytochemical and pharmacological investigations

    Directory of Open Access Journals (Sweden)

    Y. Amirazodi

    2017-11-01

    Full Text Available Background and objectives: Phyllanthus emblica L. (Phyllanthaceae, commonly known as Indian gooseberry, is an endemic plant to the tropical and subtropical areas in china, India and Thailand. The plant is extensively used in Chinese, Ayurveda, and traditional Persian medicine (TPM. In addition, there are numerous reports on pharmacological and clinical activities of gooseberry in current medicine. The present review was performed to compile the phytochemical and pharmacological data on P. emblica in order to draw a window for further research.  Methods: Databases such as Scopus, ScienceDirect and PubMed were searched for the term “P. emblica” up to 1st September, 2017. Papers concerning pharmacology and phytochemistry of the plant were gathered and analyzed. On the contrary, agriculture and genetic contents were excluded. Results: Over all, 80 papers were selected. The herb revealed to possess anti-diabetic, anti-oxidant, anti-proliferative, anti-inflammatory, antidepressant, larvicidal, anti-asthmatic, antiulcer, anti-aging, anti-carcinogenic, anti-tumor, anti-genotoxicity, anti-microbial, anticholinergic, antispasmodic, gastroprotective, anti-plasmodia, and antinociceptive activities as well as antidote effect against certain elements. The fruits are also useful in brain and gastrointestinal diseases and can be beneficial in hearth protection. Remarkably, many of those properties have been mentioned in TPM manuscripts.  Conclusion: Despite numerous pharmacological activities for P. emblica, there is still a gap between the in vivo and human studies which should be covered by more comprehensive and complementary studies. Many compounds have been isolated and elucidated from this plant which can be good candidates for various related activities and also as new natural medicaments in novel drug discovery.

  14. Marrubium vulgare L.: A review on phytochemical and pharmacological aspects

    Directory of Open Access Journals (Sweden)

    Santram Lodhi

    2017-12-01

    Full Text Available Marrubium vulgare L. (family: Lamiaceae, also known as white horehound, is widely used as herbal remedy for chronic coughs and colds. It is used in various disorders related to skin, liver, gastric, heart and immune system. This review abridges phytochemical, pharmacological studies and medicinal uses of M. vulgare and provides scientific proof for various ethnobotanical claims in order to identify gaps, which will give impulsion for novel research on M. vulgare based herbal medicines. This review summarizes selected scientific evidence on phytochemistry and pharmacological properties of M. vulgare over the past 48 years (1968 to 2016. The work reported on M. vulgare was reviewed from various sources like books, internet source i.e. google search engine, pubmed, sciencedirect and chemical abstract. The exhaustive literature was studied and critical analysis was done according to their phytochemical and pharmacological properties. Phytochemical investigations on different parts of M. vulgare have been reported the presence of flavonoids, steroids, terpenoids, tannins, saponins and volatile oils (0.05%. The aerial parts contain marrubiin, together with ursolic acid and choline. Pharmacological activities like, anti-nociceptive, anti-spasmodic, anti-hypertensive, anti-diabetic, gastroprotective, anti-inflammatory, anti-microbial, anti-cancer, antioxidant, and anti-hepatotoxic activity have been reported. M. vulgare has therapeutic potential in the treatment of inflammatory conditions, liver disorders, pain, cardiovascular, gastric and diabetic conditions. Aerial parts of M. vulgare is a good source of labdane type diterpene especially marrubiin which is present in high concentrations. However, further scientific studies are needed to explore clinical efficacy, toxicity and to explore the therapeutic effect of major secondary metabolites like diterpenes, phenylpropanoid and phenylethanoid glycosides of M. vulgare. [J Complement Med Res 2017; 6

  15. MATHEMATICAL MODELING OF AC ELECTRIC POINT MOTOR

    Directory of Open Access Journals (Sweden)

    S. YU. Buryak

    2014-03-01

    Full Text Available Purpose. In order to ensure reliability, security, and the most important the continuity of the transportation process, it is necessary to develop, implement, and then improve the automated methods of diagnostic mechanisms, devices and rail transport systems. Only systems that operate in real time mode and transmit data on the instantaneous state of the control objects can timely detect any faults and thus provide additional time for their correction by railway employees. Turnouts are one of the most important and responsible components, and therefore require the development and implementation of such diagnostics system.Methodology. Achieving the goal of monitoring and control of railway automation objects in real time is possible only with the use of an automated process of the objects state diagnosing. For this we need to know the diagnostic features of a control object, which determine its state at any given time. The most rational way of remote diagnostics is the shape and current spectrum analysis that flows in the power circuits of railway automatics. Turnouts include electric motors, which are powered by electric circuits, and the shape of the current curve depends on both the condition of the electric motor, and the conditions of the turnout maintenance. Findings. For the research and analysis of AC electric point motor it was developed its mathematical model. The calculation of parameters and interdependencies between the main factors affecting the operation of the asynchronous machine was conducted. The results of the model operation in the form of time dependences of the waveform curves of current on the load on engine shaft were obtained. Originality. During simulation the model of AC electric point motor, which satisfies the conditions of adequacy was built. Practical value. On the basis of the constructed model we can study the AC motor in various mode of operation, record and analyze current curve, as a response to various changes

  16. AC susceptibility enhancement studies in magnetic systems

    International Nuclear Information System (INIS)

    Mukherjee, S.; Ranganathan, R.; Chakravarti, A.; Sil, S.

    2001-01-01

    Enhancement of AC susceptibility has been observed for typical ferromagnets (Gd), reentrant spin glasses like (Fe 1.5 Mn 1.5 Si) and canted spin systems (Ce(Fe 0.96 Al 0.04 ) 2 ). The data have been interpreted with the help of a simulation model based on dry friction-like pinning of domain walls for systems having ferromagnetic domain structures. A strong pinning mechanism appears in the reentrant spin glass like and canted spin systems at low temperatures in addition to the intrinsic one in the ferromagnetic phase. The temperature variation of the pinning potential has been given qualitatively for the reentrant spin glass like systems

  17. Protection of AC and DC Microgrids

    DEFF Research Database (Denmark)

    Beheshtaein, Siavash; Savaghebi, Mehdi; Quintero, Juan Carlos Vasquez

    2015-01-01

    and DC microgrids, and then investigates the existing and promising solutions for the corresponding challenges. To the authors’ knowledge, three parts of smart grids are required to be developed to facilitate implementation of protection scheme in microgrids. The main requirements and open issues......In future, distributed energy resources (RESs) will be utilized at consumption points. As a consequence, power flow and fault current would be bidirectional and topologydependent; and hence the conventional protection strategies would be inefficient. This paper categorizes the main challenges in AC...

  18. Flexible AC transmission systems modelling and control

    CERN Document Server

    Zhang, Xiao-Ping; Pal, Bikash

    2012-01-01

    The extended and revised second edition of this successful monograph presents advanced modeling, analysis and control techniques of Flexible AC Transmission Systems (FACTS). The book covers comprehensively a range of power-system control problems: from steady-state voltage and power flow control, to voltage and reactive power control, to voltage stability control, to small signal stability control using FACTS controllers. In the six years since the first edition of the book has been published research on the FACTS has continued to flourish while renewable energy has developed into a mature and

  19. DC injection into low voltage AC networks

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report summarises the results of a study investigating the impact of levels of injected DC current injections on a low voltage AC distribution network systems in order to recommend acceptable limits of DC from microgeneration. Relevant literature is reviewed, and the impact of DC levels in distribution transformers, transformer modelling, and instrumental transformers are discussed. The impact of DC in residual current devices (RCD) and in domestic electricity watt hour meters is examined along with DC enhanced corrosion, corrosion failure, and the measurement of DC current injection. Sources of DC injection outlined include DC from computer power supplies, network faults, geomagnetic phenomena, lighting circuits/dimmers, and embedded generators.

  20. Brain connectivity in pathological and pharmacological coma

    Directory of Open Access Journals (Sweden)

    Quentin Noirhomme

    2010-12-01

    Full Text Available Recent studies in patients with disorders of consciousness (DOC tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low level cortical activation in response to external stimulation in patients in a vegetative state or unresponsive wakefulness syndrome. While activation of these primary sensory cortices does not necessarily reflect conscious awareness, activation in higher order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread fronto-parietal global neuronal workspace in DOC patients including the midline default mode network, ‘intrinsic’ system, and the lateral frontoparietal cortices or ‘extrinsic system’. Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between intrinsic and extrinsic brain networks.

  1. Three-Level AC-DC-AC Z-Source Converter Using Reduced Passive Component Count

    DEFF Research Database (Denmark)

    Loh, Poh Chiang; Gao, Feng; Tan, Pee-Chin

    2009-01-01

    This paper presents a three-level ac-dc-ac Z-source converter with output voltage buck-boost capability. The converter is implemented by connecting a low-cost front-end diode rectifier to a neutral-point-clamped inverter through a single X-shaped LC impedance network. The inverter is controlled...... to switch with a three-level output voltage, where the middle neutral potential is uniquely tapped from the star-point of a wye-connected capacitive filter placed before the front-end diode rectifier for input current filtering. Through careful control, the resulting converter can produce the correct volt...

  2. Cardiovascular outcomes after pharmacologic stress myocardial perfusion imaging.

    Science.gov (United States)

    Lee, Douglas S; Husain, Mansoor; Wang, Xuesong; Austin, Peter C; Iwanochko, Robert M

    2016-04-01

    While pharmacologic stress single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is used for noninvasive evaluation of patients who are unable to perform treadmill exercise, its impact on net reclassification improvement (NRI) of prognosis is unknown. We evaluated the prognostic value of pharmacologic stress MPI for prediction of cardiovascular death or non-fatal myocardial infarction (MI) within 1 year at a single-center, university-based laboratory. We examined continuous and categorical NRI of pharmacologic SPECT-MPI for prediction of outcomes beyond clinical factors alone. Six thousand two hundred forty patients (median age 66 years [IQR 56-74], 3466 men) were studied and followed for 5963 person-years. SPECT-MPI variables associated with increased risk of cardiovascular death or non-fatal MI included summed stress score, stress ST-shift, and post-stress resting left ventricular ejection fraction ≤50%. Compared to a clinical model which included age, sex, cardiovascular disease, risk factors, and medications, model χ(2) (210.5 vs. 281.9, P statistic (0.74 vs. 0.78, P stress score, stress ST-shift and stress resting left ventricular ejection fraction). SPECT-MPI predictors increased continuous NRI by 49.4% (P 3% annualized risk of cardiovascular death or non-fatal MI, yielded a 15.0% improvement in NRI (95% CI 7.6%-27.6%, P stress MPI substantially improved net reclassification of cardiovascular death or MI risk beyond that afforded by clinical factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Learning of medical pharmacology via innovation:a personal experience at McMaster and in Asia

    Institute of Scientific and Technical Information of China (English)

    Chiu-yin KWAN

    2004-01-01

    Pharmacology in the traditional medical curriculum has been treated as a discrete "preclinical" discipline identifying itself distinctly different from the other preclinical sciences or clinical subjects in knowledge base as well as learning/teaching instructions. It is usually run in series with other pre-clinical courses (eg, anatomy, biochemistry,physiology etc), but in parallel with other paraclinical courses such as pathology, microbiology and community medicine. Clinical pharmacology was only introduced relatively recently designed to overcome the perceived deficiency in "preclinical" pharmacology regarding its therapeutic relevance and application to medicine. In many universities, both preclinical and clinical pharmacology courses co-exist, usually independently offered by two separate, sometimes non-interacting Departments of Pharmacology and Clinical Pharmacology. In this model,pharmacology is generally taught in a teacher-centered, discipline-oriented, and knowledge-based curriculum.Furthermore, pharmacology courses are commonly taught by "expert" teachers, who usually engage in excessiveteaching, often adopt a knowledge-based approach in both instruction and assessment, and frequently evade or ignore clinical relevance. The clinical relevance of the pharmacological sciences is sometimes also taught in a didactic and problem-solving manner, although it is usually case-oriented. In recent years, problem-based medical curricula have emerged, in varying forms, as a platform in which pharmacology is viewed as an integrated component in a holistic approach to medical education. In this problem-based learning (PBL) model, pharmacology is learned in a student-centered environment, based on self-directed, clinically relevant and case-oriented approach,usually in a small-group tutorial format. In PBL, pharmacology is learned in concert with other subject issues relevant to the case-problem in question, such as anatomy, physiology, pathology, microbiology

  4. Transcranial Alternating Current Stimulation (tACS Mechanisms and Protocols

    Directory of Open Access Journals (Sweden)

    Amir V. Tavakoli

    2017-09-01

    Full Text Available Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding.

  5. Urine storage under refrigeration preserves the sample in chemical, cellularity and bacteriuria analysis of ACS

    Directory of Open Access Journals (Sweden)

    Karen Cristina Barcellos Ribeiro

    2013-12-01

    Full Text Available INTRODUCTION: The analysis of urine abnormal constituents and sediment (ACS comprises tests of great diagnostic and prognostic value in clinical practice. When the analysis of ACS cannot be performed within two hours after collection, the sample must be preserved in order to avoid pre-analytical interferences. Refrigeration is the most applied technique due to its cost effectiveness. Moreover, it presents fewer inconveniences when compared to chemical preservation. However, changes in ACS may also occur in samples under refrigeration. OBJECTIVE: To analyze the influence of refrigeration at 2 to 8ºC on the storage of urine samples within 24 hours. MATERIAL AND METHOD: A total of 80 urine samples were selected from patients admitted at Universidade Federal de Juiz de Fora (UFJF university hospital, which were tested for ACS at room temperature and stored under refrigeration for 6, 12 and 24 hours. RESULTS: The results showed that refrigeration proved to be effective when compared to samples kept at room temperature, inasmuch as the physical, chemical, microbial and cellularity features were preserved. Nevertheless, crystalluria was present after a 6- hour storage period. CONCLUSION: The tests revealed that cooling preserved cellularity and chemical characteristics of urine samples for up to 12 hours. Nonetheless, the precipitation of crystals was evident in this storage method. Thus, the possible consequences of storing urine samples for ACS test under these conditions should be included in the analysis report.

  6. Pharmacologic management of neuropathic pain.

    Science.gov (United States)

    Gordon, Debra B; Love, Georgette

    2004-12-01

    The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

  7. Pharmacological treatment of tics in Gilles de la Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Andrea E. Cavanna

    2011-12-01

    Full Text Available Tourette syndrome is a neurodevelopmental disorder characterised by the chronic presence of multiple motor tics (e.g. eye blinking, shoulder shrugging, etc. and at least one vocal/phonic tic (e.g. grunting or sniffing. The clinical picture of patients with Tourette syndrome is often complicated by tic-related behavioural problems and associated psychopathology. The pathophysiology of Tourette syndrome is poorly understood, however converging evidence from neuroimaging studies suggests abnormalities within the fronto-striatal pathways. The pharmacological management of the tic symptoms focuses on the dopaminergic and noradrenergic pathways and aims to improve the health-related quality of life of patients.

  8. A review on dronedarone: Pharmacological, pharmacodynamic and pharmacokinetic profile

    Directory of Open Access Journals (Sweden)

    Farah Iram

    2016-03-01

    Full Text Available Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovascular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, flecainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for dronedarone is Multaq (Sanofi Aventis. This article briefly highlights the important pharmacological, pharmacodynamic and pharmacokinetic properties of dronedarone.

  9. Dysport: pharmacological properties and factors that influence toxin action.

    Science.gov (United States)

    Pickett, Andy

    2009-10-01

    The pharmacological properties of Dysport that influence toxin action are reviewed and compared with other botulinum toxin products. In particular, the subject of diffusion is examined and discussed based upon the evidence that currently exists, both from laboratory studies and from clinical data. Diffusion of botulinum toxin products is not related to the size of the toxin complex in the product since the complex dissociates under physiological conditions, releasing the naked neurotoxin to act. The active neurotoxin in Type A products is the same and therefore diffusion is equal when equal doses are administered.

  10. Bifurcation theory of ac electric arcing

    International Nuclear Information System (INIS)

    Christen, Thomas; Peinke, Emanuel

    2012-01-01

    The performance of alternating current (ac) electric arcing devices is related to arc extinction or its re-ignition at zero crossings of the current (so-called ‘current zero’, CZ). Theoretical investigations thus usually focus on the transient behaviour of arcs near CZ, e.g. by solving the modelling differential equations in the vicinity of CZ. This paper proposes as an alternative approach to investigate global mathematical properties of the underlying periodically driven dynamic system describing the electric circuit containing the arcing device. For instance, the uniqueness of the trivial solution associated with the insulating state indicates the extinction of any arc. The existence of non-trivial attractors (typically a time-periodic state) points to a re-ignition of certain arcs. The performance regions of arcing devices, such as circuit breakers and arc torches, can thus be identified with the regions of absence and existence, respectively, of non-trivial attractors. Most important for applications, the boundary of a performance region in the model parameter space is then associated with the bifurcation of the non-trivial attractors. The concept is illustrated for simple black-box arc models, such as the Mayr and the Cassie model, by calculating for various cases the performance boundaries associated with the bifurcation of ac arcs. (paper)

  11. A nonlinear model for AC induced corrosion

    Directory of Open Access Journals (Sweden)

    N. Ida

    2012-09-01

    Full Text Available The modeling of corrosion poses particular difficulties. The understanding of corrosion as an electrochemical process has led to simple capacitive-resistive models that take into account the resistance of the electrolytic cell and the capacitive effect of the surface potential at the interface between conductors and the electrolyte. In some models nonlinear conduction effects have been added to account for more complex observed behavior. While these models are sufficient to describe the behavior in systems with cathodic protection, the behavior in the presence of induced AC currents from power lines and from RF sources cannot be accounted for and are insufficient to describe the effects observed in the field. Field observations have shown that a rectifying effect exists that affects the cathodic protection potential and this effect is responsible for corrosion in the presence of AC currents. The rectifying effects of the metal-corrosion interface are totally missing from current models. This work proposes a nonlinear model based on finite element analysis that takes into account the nonlinear behavior of the metal-oxide interface and promises to improve modeling by including the rectification effects at the interface.

  12. Measuring Gravitational Flexion in ACS Clusters

    Science.gov (United States)

    Goldberg, David

    2005-07-01

    We propose measurement of the gravitational "Flexion" signal in ACS cluster images. The flexion, or "arciness" of a lensed background galaxy arises from variations in the lensing field. As a result, it is extremely sensitive to small scale perturbations in the field, and thus, to substructure in clusters. Moreover, because flexion represents gravitationally induced asymmetries in the lensed image, it is completely separable from traditional measurements of shear, which focus on the induced ellipticity of the image, and thus, the two signals may be extracted simultaneously. Since typical galaxies are roughly symmetric upon 180 degree rotation, even a small induced flexion can potentially produce a noticeable effect {Goldberg & Bacon, 2005}. We propose the measurement of substructure within approximately 4 clusters with high-quality ACS data, and will further apply a test of a new tomographic technique whereby comparisons of lensed arcs at different redshifts may be used to estimate the background cosmology, and thus place constraints on the equation of state of dark energy.

  13. Pharmacologic management of neuropathic pain: Evidence-based recommendations

    DEFF Research Database (Denmark)

    Dworkin, Robert H.; O'Connor, Alec B.; Backonja, Miroslav

    2007-01-01

    Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered...... and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second......, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs...

  14. Pharmacologic studies in vulnerable populations: Using the pediatric experience.

    Science.gov (United States)

    Zimmerman, Kanecia; Gonzalez, Daniel; Swamy, Geeta K; Cohen-Wolkowiez, Michael

    2015-11-01

    Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics, innovative clinical trial design, use of quantitative clinical pharmacology methods, pediatric thought leadership, and collaboration have successfully overcome many existing barriers. This success has resulted in improved knowledge on pharmacokinetics, safety, and efficacy of therapeutics in children. To date, research in pregnant women has not been characterized by similar success. Wide gaps in knowledge remain despite the common use of therapeutics in pregnancy. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Deletion of the AcMNPV core gene ac109 results in budded virions that are non-infectious

    International Nuclear Information System (INIS)

    Fang Minggang; Nie, Yingchao; Theilmann, David A.

    2009-01-01

    Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac109 is a core gene and its function in the virus life cycle is unknown. To determine its role in the baculovirus life cycle, we used the AcMNPV bacmid system to generate an ac109 deletion virus (vAc 109KO ). Fluorescence and light microscopy showed that transfection of vAc 109KO results in a single-cell infection phenotype. Viral DNA replication is unaffected and the development of occlusion bodies in vAc 109KO -transfected cells evidenced progression to the very late phases of viral infection. Western blot and confocal immunofluorescence analysis showed that AC109 is expressed in the cytoplasm and nucleus throughout infection. In addition, AC109 is a structural protein as it was detected in both budded virus (BV) and occlusion derived virus in both the envelope and nucleocapsid fractions. Titration assays by qPCR and TCID 50 showed that vAc 109KO produced BV but the virions are non-infectious. The vAc 109KO BV were indistinguishable from the BV of repaired and wild type control viruses as determined by negative staining and electron microscopy.

  16. Pharmacological stress agents in nuclear cardiology

    International Nuclear Information System (INIS)

    Buscombe, J.R.

    2004-01-01

    Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. However there are a group of patients who may not be able to undergo treadmill tests. Patients with underlying conditions like neuromuscular disease, musculoskeletal disorder, heart failure and end-stage renal disease (ESRD) on renal dialysis would find it difficult to perform exercise on a treadmill or bicycle ergometer. These conditions prevent them from performing adequate exercise. Such patients would benefit from pharmacological stress procedures combined with MPS. Nuclear medicine departments use various pharmacological agents while performing stress tests on cardiac patients. The most commonly used pharmacological agents for cardiac stress are coronary vasodilators and catecholamines. In addition to these agents, adjuvant use of nitrates and atropine is also a common practice in nuclear cardiology. This review addresses various physiological and pharmacological properties of the commonly used pharmacological stress agents in MPS and critically analyses their advantages and disadvantages, as well as their safety and efficacy. (author)

  17. 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.

  18. Pharmacological screening technologies for venom peptide discovery.

    Science.gov (United States)

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

    2017-12-01

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

  19. Modeling and reliability analysis of three phase z-source AC-AC converter

    Directory of Open Access Journals (Sweden)

    Prasad Hanuman

    2017-12-01

    Full Text Available This paper presents the small signal modeling using the state space averaging technique and reliability analysis of a three-phase z-source ac-ac converter. By controlling the shoot-through duty ratio, it can operate in buck-boost mode and maintain desired output voltage during voltage sag and surge condition. It has faster dynamic response and higher efficiency as compared to the traditional voltage regulator. Small signal analysis derives different control transfer functions and this leads to design a suitable controller for a closed loop system during supply voltage variation. The closed loop system of the converter with a PID controller eliminates the transients in output voltage and provides steady state regulated output. The proposed model designed in the RT-LAB and executed in a field programming gate array (FPGA-based real-time digital simulator at a fixedtime step of 10 μs and a constant switching frequency of 10 kHz. The simulator was developed using very high speed integrated circuit hardware description language (VHDL, making it versatile and moveable. Hardware-in-the-loop (HIL simulation results are presented to justify the MATLAB simulation results during supply voltage variation of the three phase z-source ac-ac converter. The reliability analysis has been applied to the converter to find out the failure rate of its different components.

  20. Modern strategy and prospects in pharmacological treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    А. V. Kutsak

    2017-02-01

    Full Text Available Aim – to analyze scientific literature to summarize data about contemporary views on the pharmacological therapy of Parkinson's disease (PD. PD is a chronic, neurodegenerative steadily progressive disease of the central nervous system, primarily associated with the degeneration of dopamine-producing neurons in the cerebral pulp, manifested by motor and non-motor disorders and leading to permanent disability. The duration of patient’s life with PD, provided with adequate treatment, can be closer to the one of the general population. At the same time, the course of the disease may change with the increase of life expectancy of the patients. And as the result, in the clinical picture, non-motor disorders and motor complications caused by a further degeneration of dopaminergic neurons and adverse reactions of pharmacological therapy, come out in the first place. The apropos and rational correction of which improves the course of the disease and patients' quality of life. Within the age PD frequency in the population is increasing; taking into account the global trend to an increase in the duration of human life, this disease performs even bigger medical and social problem. And the need for further development of pharmacotherapy practices becomes more relevant. This review presents the current recommendations for the pharmacological treatment of PD. The attention is directed to the need for evidence when assessing the effectiveness of any treatment strategy. The data on the ongoing development of pharmaceuticals. Conclusions. At this time the existing therapeutic tactics in the pharmacological therapy of BP, despite the fact that they are quite successful in leveling manifestations of the disease, do not stop the disease, and are in fact symptomatic treatment. All successful clinical development, for the time being, are the emergence of new drugs belonging to the group of BP symptomatic therapy with the best bioavailability and tolerability

  1. Pharmacological modulation of arterial stiffness.

    LENUS (Irish Health Repository)

    Boutouyrie, Pierre

    2011-09-10

    Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for \\'de-stiffening drugs\\

  2. Pharmacological Treatments in Pathological Gambling

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2012-01-01

    AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved...... pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean...... demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behavior. CONCLUSIONS: Given that several...

  3. Pharmacological treatment of tic disorders and Tourette Syndrome.

    Science.gov (United States)

    Roessner, Veit; Schoenefeld, Katja; Buse, Judith; Bender, Stephan; Ehrlich, Stefan; Münchau, Alexander

    2013-05-01

    The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug trials in TS patients fulfilling evidence based medicine standards are still scarce. Treatment decisions are often guided by individual needs and personal experience of treating clinicians. The present recommendations for pharmacological tic treatment are therefore based on both scientific evidence and expert opinion. As first-line treatment of tics risperidone (best evidence level for atypical antipsychotics) or tiapride (largest clinical experience in Europe and low rate of adverse reactions) are recommended. Aripiprazole (still limited but promising data with low risk for adverse reactions) and pimozide (best evidence of the typical antipsychotics) are agents of second choice. In TS patients with comorbid attention deficit hyperactivity disorder (ADHD) atomoxetine, stimulants or clonidine should be considered, or, if tics are severe, a combination of stimulants and risperidone. When mild to moderate tics are associated with obsessive-compulsive symptoms, depression or anxiety sulpiride monotherapy can be helpful. In more severe cases the combination of risperidone and a selective serotonin reuptake inhibitor should be given. In summary, further studies, particularly randomized, double-blind, placebo-controlled trials including larger and/or more homogenous patient groups over longer periods are urgently needed to enhance the scientific basis for drug treatment in tic disorders. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria.

    Science.gov (United States)

    Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina

    2016-03-01

    Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.

  5. AC losses in high Tc superconductors

    International Nuclear Information System (INIS)

    Campbell, A.M.

    1998-01-01

    Full text: Although in principle the AC losses in high Tc superconductors can be calculated from the critical current density, a number of complications make this difficult. The Jc is very field dependent, there are intergranular and intragranular critical currents, the material is anisotropic and there is usually a large demagnetising factor. Care must be taken in interpreting electrical measurements since the voltage depends on the position of the contacts. In spite of these complications the simple theory of Norris has proved surprisingly successful and arguments will be presented as to why this is the case. Results on a range of tapes will be compared with theory and numerical methods for predicting losses discussed. Finally a theory for coupling losses will be given for a composite conductor with high resistance barriers round the filaments

  6. Transcranial alternating current stimulation (tACS

    Directory of Open Access Journals (Sweden)

    Andrea eAntal

    2013-06-01

    Full Text Available Transcranial alternating current stimulation (tACS seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency or desynchronize (e.g. by the application of several frequencies cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the ripple range induces intensity dependent inhibition or excitation in the motor cortex most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

  7. Ac loss measurement of SSC dipole magnets

    International Nuclear Information System (INIS)

    Delchamps, S.; Hanft, R.; Jaffery, T.; Kinney, W.; Koska, W.; Lamm, M.J.; Mazur, P.O.; Orris, D.; Ozelis, J.P.; Strait, J.; Wake, M.

    1992-09-01

    AC losses in full length and 1.5 m model SSC collider dipoles were successfully measured by the direct observation of energy flow into and out of magnets during a ramp cycle. The measurement was performed by using two double-integrating type digital volt meters (DVM's) for current and voltage measurement. Measurements were performed for six is m long ASST magnets and five 1.5 m long model magnets, inducting one 40 mm diameter magnet. There were large variations in the eddy current losses. Since these magnets use conductors with slight deviations in their internal structures and processing of the copper surface depending on the manufacturer, it is likely that there are differences in the contact resistance between strands. Correlation between the ramp rate dependence of the,quench current and the eddy current loss was evident

  8. Effective Peroxidase-Like Activity of Co-Aminoclay [CoAC] and Its Application for Glucose Detection

    Directory of Open Access Journals (Sweden)

    Han Pill Song

    2018-02-01

    Full Text Available In this study, we describe a novel peroxidase-like activity of Co-aminoclay [CoAC] present at pH ~5.0 and its application to fluorescent biosensor for the determination of H2O2 and glucose. It is synthesized with aminoclays (ACs entrapping cationic metals such as Fe, Cu, Al, Co., Ce, Ni, Mn, and Zn to find enzyme mimicking ACs by sol–gel ambient conditions. Through the screening of catalytic activities by the typical colorimetric reaction employing 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic aciddiammonium salt (ABTS as a substrate with or without H2O2, Fe, Cu, and CoACs are found to exhibit peroxidase-like activity, as well as oxidase-like activity was observed from Ce and MnACs. Among them, CoAC shows exceptionally high peroxidase-like activity, presumably due to its ability to induce electron transfer between substrates and H2O2. CoAC is then used to catalyze the oxidation of Amplex® UltraRed (AUR into a fluorescent end product, which enables a sensitive fluorescent detection of H2O2. Moreover, a highly sensitive and selective glucose biosensing strategy is developed, based on enzyme cascade reaction between glucose oxidase (GOx and CoAC. Using this strategy, a highly linear fluorescence enhancement is verified when the concentration of glucose is increased in a wide range from 10 μM to 1 mM with a lower detection limit of 5 μM. The practical diagnostic capability of the assay system is also verified by its use to detect glucose in human blood serum. Based on these results, it is anticipated that CoAC can serve as potent peroxidase mimetics for the detection of clinically important target molecules.

  9. Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

    Science.gov (United States)

    Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

    2018-02-01

    Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, pLearning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    Directory of Open Access Journals (Sweden)

    Rianne A. de Kleine

    2013-10-01

    Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

  11. Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

    Directory of Open Access Journals (Sweden)

    Elga Esposito

    2015-01-01

    Full Text Available Beyond reperfusion therapies, there are still no widely effective therapies for ischemic stroke. Although much progress has been made to define the molecular pathways involved, targeted neuroprotective strategies have often failed in clinical trials. An emerging hypothesis suggests that focusing on single targets and mechanisms may not work since ischemic stroke triggers multiple pathways in multiple cell types. In this review, we briefly survey and assess the opportunities that may be afforded by pre- and postconditioning therapies, with particular attention to pharmacologic pre- and postconditioning. Pharmacologic conditioning may be defined as the use of chemical agents either before or shortly after stroke onset to trigger mechanisms of endogenous tolerance that are thought to involve evolutionarily conserved signals that offer broad protection against ischemia. Importantly, many of the pharmacologic agents may also have been previously used in humans, thus providing hope for translating basic mechanisms into clinical applications.

  12. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.

    Science.gov (United States)

    de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes

    2013-10-17

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

  13. Ac irreversibility line of bismuth-based high temperature superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Mehdaoui, A. [Laboratoire de Physique et de Spectroscopie Electronique, URA 1435 Faculte des Sciences, Universite de Haute Alsace 4, rue des Freres Lumiere, 68093 Mulhouse Cedex (France); Beille, J. [Laboratoire Louis Neel, CNRS, BP 166, 38042 Grenoble Cedex 9 (France); Berling, D.; Loegel, B. [Laboratoire de Physique et de Spectroscopie Electronique, URA 1435 Faculte des Sciences, Universite de Haute Alsace 4, rue des Freres Lumiere, 68093 Mulhouse Cedex (France); Noudem, J.G.; Tournier, R. [EPM-MATFORMAG, Laboratoire dElaboration par Procede Magnetique, CNRS, BP 166, 38042 Grenoble Cedex 9 (France)

    1997-09-01

    We discuss the magnetic properties of lead doped Bi-2223 bulk samples obtained through combined magnetic melt texturing and hot pressing (MMTHP). The ac complex susceptibility measurements are achieved over a broad ac field range (1 Oe{lt}h{sub ac}{lt}100 Oe) and show highly anisotropic properties. The intergranular coupling is improved in the direction perpendicular to the applied stress and magnetic field direction, and an intragranular loss peak is observed for the first time. A comparison is made with other bismuth-based compounds and it is shown that the MMTHP process shifts the ac irreversibility line (ac IL) toward higher fields. It is also shown that all the ac IL{close_quote}s for quasi 2D bismuth-based compounds show a nearly quadratic temperature dependence and deviate therefore strongly from the linear behavior observed in quasi 3D compounds and expected from a critical state model.{copyright} {ital 1997 Materials Research Society.}

  14. Ac irreversibility line of bismuth-based high temperature superconductors

    International Nuclear Information System (INIS)

    Mehdaoui, A.; Beille, J.; Berling, D.; Loegel, B.; Noudem, J.G.; Tournier, R.

    1997-01-01

    We discuss the magnetic properties of lead doped Bi-2223 bulk samples obtained through combined magnetic melt texturing and hot pressing (MMTHP). The ac complex susceptibility measurements are achieved over a broad ac field range (1 Oe ac <100 Oe) and show highly anisotropic properties. The intergranular coupling is improved in the direction perpendicular to the applied stress and magnetic field direction, and an intragranular loss peak is observed for the first time. A comparison is made with other bismuth-based compounds and it is shown that the MMTHP process shifts the ac irreversibility line (ac IL) toward higher fields. It is also shown that all the ac IL close-quote s for quasi 2D bismuth-based compounds show a nearly quadratic temperature dependence and deviate therefore strongly from the linear behavior observed in quasi 3D compounds and expected from a critical state model.copyright 1997 Materials Research Society

  15. AC conductivity and dielectric behavior of bulk Furfurylidenemalononitrile

    Science.gov (United States)

    El-Nahass, M. M.; Ali, H. A. M.

    2012-06-01

    AC conductivity and dielectric behavior for bulk Furfurylidenemalononitrile have been studied over a temperature range (293-333 K) and frequency range (50-5×106 Hz). The frequency dependence of ac conductivity, σac, has been investigated by the universal power law, σac(ω)=Aωs. The variation of the frequency exponent (s) with temperature was analyzed in terms of different conduction mechanisms, and it was found that the correlated barrier hopping (CBH) model is the predominant conduction mechanism. The temperature dependence of σac(ω) showed a linear increase with the increase in temperature at different frequencies. The ac activation energy was determined at different frequencies. Dielectric data were analyzed using complex permittivity and complex electric modulus for bulk Furfurylidenemalononitrile at various temperatures.

  16. [The best of clinical cardiovascular pharmacology in 2005].

    Science.gov (United States)

    Ambrosi, R; Andrejak, M; Drici, M D; Herpin, D

    2006-01-01

    Although the year 2005 has reinforced the therapeutic advances of 2004, with confirmation of certain concepts, the 'coxib affair' has continued to provoke arguments between pharmaceutical companies, licensing agencies as well as patients, some of whom have amalgamated into consumer groups to reject en masse placing any responsibility on the prescribers in favour of an attack on the drug licensing process itself. Among the cardiovascular drugs that will soon be licensed, only ivabradine in stable angina, and remodulin in primary pulmonary arterial hypertension are new. The therapeutic advances in 2005 regarding platelet aggregation and blood coagulation have been significant, in the human, scientific and commercial context, while hypertension has not been ignored. Another new development is the ever more precise notion of the metabolic syndrome, a target of choice for the pharmaceutical industry. The potential range of applications has been widened to include obesity, hypertension, diabetes, HDL cholesterol... The licensing authorities find themselves facing a hurdle to overcome, with novel combinations of drugs (ACE inhibitors, calcium blockers/statins, statins/aspirin, ARA2/calcium blockers...).

  17. Portal hypertension and variceal bleeding: Clinical and pharmacological aspects

    DEFF Research Database (Denmark)

    Hobolth, Lise

    2010-01-01

    Blødende esophagus varicer er en af den mest frygtede komplikationer til cirrose og portal hypertension pga. den høje mortalitet. Et klassisk studie fra 1981 opgjorde 6-ugers mortaliteten til 42%, hvoraf 75% døde indenfor den første uge. Gennem de sidste 2-3 årtier er der introduceret en række nye...

  18. Clinical and pharmacological management of endodontic flare-up

    Directory of Open Access Journals (Sweden)

    Harikaran Jayakodi

    2012-01-01

    Full Text Available Knowledge of the causes of and mechanisms behind interappointment pain in endodontics is of utmost importance for the clinician to properly prevent or manage this undesirable condition. The causative factors of interappointment pain encompass mechanical, chemical, and microbial injuries to the pulp or periradicular tissues, which are induced or exacerbated during root canal treatment. This review article underlines the various treatment modalities for relief of pain and swelling in such situations, including premedication, drainage establishment, relief of occlusion, and intracanal and systemic medication.

  19. Clinical and pharmacological management of endodontic flare-up

    OpenAIRE

    Jayakodi, Harikaran; Kailasam, Sivakumar; Kumaravadivel, Karthick; Thangavelu, Boopathi; Mathew, Sabeena

    2012-01-01

    Knowledge of the causes of and mechanisms behind interappointment pain in endodontics is of utmost importance for the clinician to properly prevent or manage this undesirable condition. The causative factors of interappointment pain encompass mechanical, chemical, and microbial injuries to the pulp or periradicular tissues, which are induced or exacerbated during root canal treatment. This review article underlines the various treatment modalities for relief of pain and swelling in such situa...

  20. Clinical and pharmacological management of endodontic flare-up.

    Science.gov (United States)

    Jayakodi, Harikaran; Kailasam, Sivakumar; Kumaravadivel, Karthick; Thangavelu, Boopathi; Mathew, Sabeena

    2012-08-01

    Knowledge of the causes of and mechanisms behind interappointment pain in endodontics is of utmost importance for the clinician to properly prevent or manage this undesirable condition. The causative factors of interappointment pain encompass mechanical, chemical, and microbial injuries to the pulp or periradicular tissues, which are induced or exacerbated during root canal treatment. This review article underlines the various treatment modalities for relief of pain and swelling in such situations, including premedication, drainage establishment, relief of occlusion, and intracanal and systemic medication.

  1. Clinical pharmacology of novel anticancer agents : Focus on oral formulations

    NARCIS (Netherlands)

    de Weger, V.A.

    2017-01-01

    The taxanes paclitaxel and docetaxel have a low oral bioavailability, as a result of poor water solubility and high first-pass effect. The water-solubility could be improved by the development of solid dispersion formulations for oral use. In this thesis it is shown that the combination of the solid

  2. Clinical pharmacology of cannabinoids in early phase drug development

    NARCIS (Netherlands)

    Zuurman, Hillie Henka

    2008-01-01

    Although cannabis is especially known for its recreational use as a ‘soft drug’, its potential therapeutic properties have been recognized for hundreds of years. Since the isolation of THC from Cannabis sativa L, the discovery of cannabinoid receptors and their natural ligands (endocannabinoids) the

  3. The clinical pharmacology of technetium diethyl-IDA

    International Nuclear Information System (INIS)

    Tjen, H.S.L.M.

    1979-01-01

    In this presentation the performance of the cholescintigraphic study is evaluated from a patho-physiological point of view. With this approach studies of bilirubin metabolism may also provide important information about the mechanisms whereby other organic compounds are transported, metabolized and excreted by the liver cells. The results indicate that diethyl-IDA is a hepatobiliary agent with excellent biological properties. The behaviour of the reagent in normal and pathological individuals can be correlated to bilirubin metabolism. The performance of the cholescintigraphic study is less dependent on the serum bilirubin level in contrast to routinely used radiologic examinations. The level of alkaline phosphatase and serum transaminases is of no influence to the performance of the examination. Combining serial scintigraphy with time-activity curves and functional images from the computer provides additional information so that a differentiation between parenchymal liver disease and bile duct obstruction can be made. (Auth.)

  4. Clinical Pharmacology of Teicoplanin in Neonates: Effects and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2016-10-01

    Full Text Available Teicoplanin is a glycoside antibiotic which consists of five closely related glycopeptide antibiotics with similar antibacterial properties to vancomycin that were first isolated in 1976. Teicoplanin is active against many gram-positive anaerobe microorganisms and is particularly potent against clostridium species. It is also active against most Listeria, enterococci and staphylococci including methicillin-resistant strains. Nonviridans and viridans streptococci, Streptococcus pneumoniae, and enterococci are inhibited by teicoplanin. Teicoplanin has been used to treat a wide variety of infections, including osteomyelitis and endocarditis caused by methicillin-resistant and methicillin-susceptible staphylococci, streptococci, and enterococci. Teicoplanin has a spectrum of antimicrobial action similar to vancomycin, but teicoplanin has some advantages in that it only needs to be given once a day, does not need to be given as slowly as vancomycin and can be given by intramuscular injection. Teicoplanin cannot be given by mouth. Teicoplanin is excreted unchanged in the urine. The half-life of teicoplanin is 100 hours in adults and 21/2 days in children. Teicoplanin has a large distribution volume and long half-life and a loading dose is recommended. In infants, the loading dose of teicoplanin is 16 mg/kg administered intravenously followed by 8 mg/kg once daily. The target trough concentration of teicoplanin ranges from 15 to 30 µg/ml. The incidence of hepatic dysfunction, renal impairment and thrombocytopenia is 14.8%, 20%, and 14%, respectively, when the serum teicoplanin concentrations range from < 20 µg/ml and ≥ 20 µg/ml. The aim of this study is to review the effects and the pharmacokinetics of teicoplanin in neonates.

  5. HIV protease inhibitors in pregnancy : pharmacology and clinical use.

    Science.gov (United States)

    Andany, Nisha; Loutfy, Mona R

    2013-03-01

    The impact of antiretroviral therapy (ART) on the natural history of HIV-1 infection has resulted in dramatic reductions in disease-associated morbidity and mortality. Additionally, the epidemiology of HIV-1 infection worldwide is changing, as women now represent a substantial proportion of infected adults. As more highly effective and tolerable antiretroviral regimens become available, and as the prevention of mother-to-child transmission becomes an attainable goal in the management of HIV-infected individuals, more and more HIV-positive women are choosing to become pregnant and have children. Consequently, it is important to consider the efficacy and safety of antiretroviral agents in pregnancy. Protease inhibitors are a common class of medication used in the treatment of HIV-1 infection and are increasingly being used in pregnancy. However, several studies have raised concerns regarding pharmacokinetic alterations in pregnancy, particularly in the third trimester, which results in suboptimal drug concentrations and a theoretically higher risk of virologic failure and perinatal transmission. Drug level reductions have been observed with each individual protease inhibitor and dose adjustments in pregnancy are suggested for certain agents. Furthermore, studies have also raised concerns regarding the safety of protease inhibitors in pregnancy, particularly as they may increase the risk of pre-term birth and metabolic disturbances. Overall, protease inhibitors are safe and effective for the treatment of HIV-infected pregnant women. Specifically, ritonavir-boosted lopinavir- and atazanavir-based regimens are preferred in pregnancy, while ritonavir-boosted darunavir- and saquinavir-based therapies are reasonable alternatives. This paper reviews the use of protease inhibitors in pregnancy, focusing on pharmacokinetic and safety considerations, and outlines the recommendations for use of this class of medication in the HIV-1-infected pregnant woman.

  6. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

  7. Clinical Pharmacology of Paracetamol in Neonates: A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici, MD, PhD

    2015-12-01

    Paracetamol clearance is lower in neonates than in children and adults. After metabolic conversion, paracetamol is subsequently eliminated by the renal route. The main metabolic conversions are conjugation with glucuronic acid and with sulphate. In the urine of neonates sulphated paracetamol concentration is higher than the glucuronidated paracetamol level, suggesting that sulfation prevails over glucuronidation in neonates. A loading dose of 20 mg/kg followed by 10 mg/kg every 6 hours of intravenous paracetamol is suggested to achieve a compartment concentration of 11 mg/L in late preterm and term neonates. Aiming for the same target concentration, oral doses are similar with rectal administration of 25 to 30 mg/kg/d in preterm neonates of 30 weeks’ gestation, 45 mg/kg/d in preterm infants of 34 weeks’ gestation, and 60 mg/kg/d in term neonates are suggested. The above-mentioned paracetamol doses for these indications (pain, fever are well tolerated in neonates, but do not result in a significant increase in liver enzymes, and do not affect blood pressure and have limited effects on heart rate. In contrast, the higher doses suggested in extreme preterm neonates to induce closure of the patent ductus arteriosus have not yet been sufficiently evaluated regarding efficacy or safety. Moreover, focussed pharmacovigilance to explore the potential causal association between paracetamol exposure during perinatal life and infancy and subsequent atopy is warranted.

  8. The Pharmacological Basis of Cannabis Therapy for Epilepsy.

    Science.gov (United States)

    Reddy, Doodipala Samba; Golub, Victoria M

    2016-04-01

    Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Pharmacogenomics of alcohol addiction: Personalizing pharmacologic treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Ragia Georgia

    2014-01-01

    Full Text Available Alcohol dependence is a serious psychiatric disorder with harmful physical, mental and social consequences, and a high probability of a chronic relapsing course. The field of pharmacologic treatment of alcohol dependence and craving is expanding rapidly; the drugs that have been found to reduce relapse rates or drinking in alcohol-dependent patients and are approved for treatment of alcohol dependence are naltrexone, acamprosate and disulfiram, whereas also topiramate appears as a promising therapy. For many patients, however, these treatments are not effective. Evidence from a number of different studies suggests that genetic variation is a significant contributor to interindividual variation of clinical presentation of alcohol problems and response to a given treatment. The aim of the present review is to summarize and discuss the findings on the association between gene polymorphisms and the response to alcohol dependence treatment medications. It is anticipated that future implementation of pharmacogenomics in clinical practice will help personalize alcohol dependence drug treatment, and development personalized hospital pharmacology.

  10. Transition towards DC micro grids: From an AC to a hybrid AC and DC energy infrastructure

    Directory of Open Access Journals (Sweden)

    Evi Ploumpidou

    2017-12-01

    Full Text Available Our electricity is predominantly powered by alternating current (AC, ever since the War of Currents ended in the favor of Nicola Tesla at the end of the 19th century. However, lots of the appliances we use, such as electronics and lights with light-emitting diode (LED technology, work internally on direct current (DC and it is projected that the number of these appliances will increase in the near future. Another contributor to the increase in DC consumption is the ongoing electrification of mobility (Electric Vehicles (EVs. At the same time, photovoltaics (PV generate DC voltages, while the most common storage technologies also use DC. In order to integrate all these appliances and technologies to the existing AC grid, there is a need for converters which introduce power losses. By distributing DC power to DC devices instead of converting it to AC first, it is possible to avoid substantial energy losses that occur every time electricity is converted. This situation initiated the concept for the implementation of the DC-Flexhouse project. A prototype DC installation will be developed and tested in one of the buildings of the developing living lab area called the District of Tomorrow (De Wijk van Morgen which is located in Heerlen, the Netherlands. A neighborhood cooperative (Vrieheide cooperatie is also part of the consortium in order to address the aspect of social acceptance. Although DC seems to be a promising solution for a more sustainable energy system, the business case is still debatable due to both technology- and market-related challenges. The current energy infrastructure is predominantly based on AC, manufacturers produce devices based on AC standards and people are using many AC products across a long life span. This Smart Energy Buildings & Cities (SEB&C PDEng project is a contribution to the DC-Flexhouse project. The aim is to analyze the challenges in the transition to DC micro grids, assess the market potential of DC

  11. Magnetic irreversibility in granular superconductors: ac susceptibility study

    International Nuclear Information System (INIS)

    Perez, F.; Obradors, X.; Fontcuberta, J.; Vallet, M.; Gonzalez-Calbet, J.

    1991-01-01

    Ac susceptibility measurements of a ceramic weak-coupled superconductor in very low ac fields (2mG, 111Hz) are reported. We present evidence for the observation of the magnetic irreversibility following a ZFC-FC thermal cycling by means of ac susceptibilty measurements. It is shown that this technique also reflect local magnetic field effects in granular superconductors, as previously suggested in microwave surface resistance and I-V characteristics. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Cecília Carboni Tardelli Cerveira

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

  13. Glaucoma: Hot Topics in Pharmacology.

    Science.gov (United States)

    Balendra, Shiama I; Shah, Parth Arvind; Jain, Mishank; Grzybowski, Andrzej; Cordeiro, Maria F

    2017-01-01

    Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods. The goal of this review was to summarize main areas of latest glaucoma research into risk factors of glaucoma, diagnostic tools and treatments. PubMed was used to search for terms including glaucoma risk factors, glaucoma diagnostics, glaucoma treatment, glaucoma drug delivery and glaucoma IOP. The evidence for risk factors of low CSF pressure, IOP, smoking, vascular risk factors and light toxicity is described. Latest diagnostic and monitoring techniques for glaucoma include SD-OCT, DARC and IOP telemetry. Current and emerging medical and surgical treatments in glaucoma are discussed. Rho kinase inhibitors have the potential to both lower IOP and also provide neuroprotection, several of which are in clinical trials. Several other new medical treatments such as calcium channel blockers and neurotrophic agents also have the capacity to provide neuroprotection. Minimally Invasive Glaucoma Surgery (MIGS) devices provide an improved safety profile compared to traditional trabeculectomy; the latest ab interno and ab externo devices are described. Novel drug delivery methods, including punctual plugs and contact lenses, help overcome the challenges with patient adherence. The ultimate goals are to reduce the individual patient risk factors associated with glaucoma, diagnose the condition early and to find treatments that not only reduce IOP but also reverse neurodegeneration of RGCs. The usage of combinations

  14. Implementation of an Outcome-Based Longitudinal Pharmacology Teaching in Undergraduate Dental Curriculum at KSAU-HS Experience

    Directory of Open Access Journals (Sweden)

    Abdulmalik M. Alkatheri

    2018-06-01

    Full Text Available Purpose/objectives: The aim of this study is to present a modification of the structure of the pharmacology educational experience for dental students as a result of the early introduction of a pharmacology course into the pre-professional curriculum. Methods: Three courses of professional dental pharmacology were modified before and/or after delivery by developing general course learning outcomes, lecture-by-lecture learning outcomes and theme mapping to align topics taught within these courses and with those taught in the pre-professional dental program. Results: Final proposals for three professional dental pharmacology courses, which are distributed over three professional years, were prepared based on teaching experience and theme mapping. Topics were added, deleted, transferred from one course to another to afford courses that are fully aligned, relatively comprehensive, longitudinal, with focus on topics relevant to the dental practice without redundancy. In addition, the design of these courses took into consideration the level of coverage of the pre-professional dental pharmacology course. Conclusions: This longitudinal inclusion of pharmacology courses form the second pre-professional year to the third professional year is expected to improve dental students’ pharmacology education experience. Although the last of these courses is a pharmacotherapeutic course, more courses with clinically oriented therapeutic approach are recommended. Keywords: Pharmacology course design, Dental students, Curriculum development, Curriculum mapping

  15. AC Own Motion Percentage of Randomly Sampled Cases

    Data.gov (United States)

    Social Security Administration — Longitudinal report detailing the numbers and percentages of Appeals Council (AC) own motion review actions taken on un-appealed favorable hearing level decisions...

  16. AC electric motors control advanced design techniques and applications

    CERN Document Server

    Giri, Fouad

    2013-01-01

    The complexity of AC motor control lies in the multivariable and nonlinear nature of AC machine dynamics. Recent advancements in control theory now make it possible to deal with long-standing problems in AC motors control. This text expertly draws on these developments to apply a wide range of model-based control designmethods to a variety of AC motors. Contributions from over thirty top researchers explain how modern control design methods can be used to achieve tight speed regulation, optimal energetic efficiency, and operation reliability and safety, by considering online state var

  17. Pharmacological therapy of chronic obstructive pulmonary disease

    African Journals Online (AJOL)

    patients with COPD require pharmacological therapy. ... pulmonary dysfunction. Clearly the patient's tolerance to the various drugs will influence the choice of long-term maintenance treatment. The other important factor in the .... blocking cervical immune responses might leave her less protected against other infections.

  18. Multidimensional Screening as a Pharmacology Laboratory Experience.

    Science.gov (United States)

    Malone, Marvin H.; And Others

    1979-01-01

    A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

  19. Radioreceptor assay: theory and applications to pharmacology

    International Nuclear Information System (INIS)

    Perret, G.; Simon, P.

    1984-01-01

    The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproductibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, β-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising [fr

  20. Ethnomedicinal uses and pharmacological activities of Croton ...

    African Journals Online (AJOL)

    Abstract. Purpose: To provide an overview of the ethnomedicinal uses and ... calls for detailed phytochemical and pharmacological properties of the species aimed at identifying the ... urban communities throughout its native ... sized, densely leafy tree reaching 15 m tall [17] ..... Williams College, United States; 1998; p 133.