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Sample records for action pharmacology effects

  1. [Pharmacological action of bromazepam suppository].

    Science.gov (United States)

    Kasama, T; Fujii, Y; Aida, Y; Mayuzumi, K; Mayuzumi, Y; Goto, M; Gomita, Y; Moriyama, M; Ichimaru, Y

    1983-02-01

    Differences between the pharmacological effects of bromazepam given by oral and rectal administration were investigated in mice and rats. 1) Bromazepam dose-dependently prolonged the sleeping time induced by thiopental-Na, ethanol and ether by both administration routes. 2) The analgesic action of bromazepam was recognized by the hot-plate method and the algolytic test. In the hot-plate test, analgesic actions of morphine and pentazocine were potentiated by bromazepam in a dose of 0.5 mg/kg by both routes. 3) The muscle relaxant effect of bromazepam administered rectally was more potent than that administered orally in the inclined screen test and the rotarod test. This effect of bromazepam by rectal administration was approximately 2 times as potent as that by oral administration. 4) Bromazepam inhibited the convulsion induced by maximum electric shock, pentylenetetrazol and picrotoxin. In pentylenetetrazol-induced convulsion, the inhibitory effect of bromazepam administered rectally was 2 times as potent as that administered orally. In the other convulsion test, no significant differences between oral and rectal administration could be recognized. 5) Hyperemotionality and muricide (mouse-killing behaviour) of rats with bilateral olfactory bulb ablations (OB rat) were reduced by oral and rectal administrations of bromazepam in a dose-dependent manner. The effects by rectal administration were more potent than that by oral administration. Bromazepam was approximately 20 times as potent as diazepam administered by the same route. Fighting behaviour in mice subjected to footshock was suppressed by rectal administration of bromazepam, and this effect was as same as that by oral administration. 6) The rate of lever pressing response in the lateral hypothalamic self-stimulation test in the Skinner box was markedly increased by rectal administration of 0.2 mg/kg bromazepam. 7) Methamphetamine-induced hyperactivity of mice was significantly suppressed only by bromazepam

  2. Pharmacological Effects of Mangiferin

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  3. Pharmacological action and mechanisms of ginkgolide B

    Institute of Scientific and Technical Information of China (English)

    XIA Shi-hai; FANG Dian-chun

    2007-01-01

    Objective To review the recent research progress in pharmacological actions and mechanisms of ginkgolide B.Data sources Information included in this article was identified by searching of PUBMED (1987-2006) online resources using the key terms "ginkgolide B", "platelet activating factor", and "pharmacological".Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.Results The key issues related to the pharmacological actions and mechanisms of ginkgolide B were summarized. The ginkgolide B possesses a number of beneficial effects such as anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects. Meantime, their mechaniams were discussed.Conclusions The Ginkgolide B is the most potent antagonist of platelet activating factor (PAF) and exhibits therapeutic action in a variety of diseases mainly by the PAF receptor.

  4. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

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    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present.

  5. [Preliminary study on the pharmacological action spicatus].

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    Gai, H; Shou, Y; Wang, J; Li, L

    1997-01-01

    In this report the pharmacological action of Spicatus was studied. The results insicated that it had diureric, antibiotic and anti-inflammatory effects, yet had Iittle toxic side-effect. It had significant inhibitory effect on crofon oil-caused mice ear swell. It also had marked diuretic effect in orcinary rats, but had Iittie effect on uric pH the rats. It exhibited certain inhibition of Staphycoloccus aureus, Eschrichia coli and Pseudomonas aeruginosa in vitro. The maximum tolerable dose test in mice showed no marked toxic effect, LD50 > 80 g/kg.

  6. The Antihyperglycemic Effects of Rhizoma Coptidis and Mechanism of Actions: A Review of Systematic Reviews and Pharmacological Research

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    Hui Wang

    2014-01-01

    Full Text Available Rhizoma Coptidis (Huang Lian in Chinese pinyin is among the most widely used traditional Chinese herbal medicines and has a profound history of more than 2000 years of being used as a therapeutic herb. The antidiabetic effects of Rhizoma Coptidis have been extensively investigated in animal experiments and clinical trials and its efficacy as a promising antihyperglycemic agent has been widely discussed. In the meantime, findings from modern pharmacological studies have contributed the majority of its bioactivities to berberine, the isoquinoline alkaloids component of the herb, and a number of experiments testing the antidiabetic effects of berberine have been initiated. Therefore, we conducted a review of the current evidence profile of the antihyperglycemic effects of Rhizoma Coptidis as well as its main component berberine and the possible mechanism of actions, in order to summarize research evidence in this area and identify future research directions.

  7. Pharmacological action of Australian animal venoms.

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    Hodgson, W C

    1997-01-01

    1. Australia has some of the most venomous fauna in the world. Although humans are not usually perceived as being predators against these animals they are often envenomated, accidentally or otherwise. This has led to the development of antivenoms against some of the potentially lethal venoms. However, further understanding of the mechanism(s) of action of these and other venoms is important, not only for developing new treatment strategies but also in the search for novel research tools. 2. The present review discusses the pharmacology of some of the components found in venoms and outlines the research undertaken on some of Australia's venomous animals, with the exception of snakes. 3. Biogenic amines, peptides and enzymes are common venom components and produce a wide range of effects in envenomated humans. For example, respiratory failure observed after envenomation by the box jellyfish (Chirnex fleckeri) and Sydney funnel-web spider (Atrax robustus) is most likely due to potent neurotoxins in the venoms. Stonefish (Synanceja trachynis) and platypus (Ornithorhynchus anatinus) venoms, although not considered lethal, cause severe pain. However, the components responsible for these effects have not been isolated. Venom components, as yet unidentified, may be responsible for the cutaneous necrotic lesions that have been reported after some spider bites (e.g. Lampona cylindrata). Other venoms, such as those of the jumper ant (Myrmecia pilosula) and bull ant (M. pyriformis), may produce only mild skin irritation to the majority of humans but a severe anaphylactic response in sensitized victims. 4. While there has been a renewed interest in toxinology, further research is required to fully elucidate the pharmacological action of many of these venoms.

  8. The mass action equation in pharmacology.

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    Kenakin, Terry

    2016-01-01

    The mass action equation is the building block from which all models of drug-receptor interaction are built. In the simplest case, the equation predicts a sigmoidal relationship between the amount of drug-receptor complex and the logarithm of the concentration of drug. The form of this function is also the same as most dose-response relationships in pharmacology (such as enzyme inhibition and the protein binding of drugs) but the potency term in dose-response relationships very often differs in meaning from the similar term in the simple mass action relationship. This is because (i) most pharmacological systems are collections of mass action reactions in series and/or in parallel and (ii) the important assumptions in the mass action reaction are violated in complex pharmacological systems. In some systems, the affinity of the receptor R for some ligand A is modified by interaction of the receptor with the allosteric ligand B and concomitantly the affinity of the receptor for ligand B is modified to the same degree. When this occurs, the observed affinity of the ligand A for the receptor will depend on both the concentration of the co-binding allosteric ligand and its nature. The relationships between drug potency in pharmacological models and the equilibrium dissociation constants defined in single mass action reactions are discussed. More detailed knowledge of efficacy has led to new models of drug action that depend on the relative probabilities of different states, and these have taken knowledge of drug-receptor interactions beyond Guldberg and Waage. © 2015 The British Pharmacological Society.

  9. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

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    Yi Liu

    2015-01-01

    Full Text Available Cordyceps sinensis, also called DongChongXiaCao (winter worm, summer grass in Chinese, is becoming increasingly popular and important in the public and scientific communities. This study summarizes the chemical constituents and their corresponding pharmacological actions of Cordyceps sinensis. Many bioactive components of Cordyceps sinensis have been extracted including nucleoside, polysaccharide, sterol, protein, amino acid, and polypeptide. In addition, these constituents’ corresponding pharmacological actions were also shown in the study such as anti-inflammatory, antioxidant, antitumour, antiapoptosis, and immunomodulatory actions. Therefore can use different effects of C. sinensis against different diseases and provide reference for the study of Cordyceps sinensis in the future.

  10. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

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    Liu, Yi; Wang, Jihui; Wang, Wei; Zhang, Hanyue; Zhang, Xuelan; Han, Chunchao

    2015-01-01

    Cordyceps sinensis, also called DongChongXiaCao (winter worm, summer grass) in Chinese, is becoming increasingly popular and important in the public and scientific communities. This study summarizes the chemical constituents and their corresponding pharmacological actions of Cordyceps sinensis. Many bioactive components of Cordyceps sinensis have been extracted including nucleoside, polysaccharide, sterol, protein, amino acid, and polypeptide. In addition, these constituents' corresponding pharmacological actions were also shown in the study such as anti-inflammatory, antioxidant, antitumour, antiapoptosis, and immunomodulatory actions. Therefore can use different effects of C. sinensis against different diseases and provide reference for the study of Cordyceps sinensis in the future. PMID:25960753

  11. Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety

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    Christoph Kellinghaus

    2009-09-01

    Full Text Available Christoph KellinghausDepartment of Neurology, Klinikum Osnabrück, GermanyAbstract: Lacosamide (LCM is a novel agent that has been developed as an antiepileptic drug. In vitro studies suggest that LCM modulates voltage-gated sodium channels by enhancing their slow inactivation. In addition, LCM seems to interact with collapsin-response mediator protein 2 and thus may mediate neuronal plasticity. LCM has an elimination half-life of 13 hours, no relevant protein binding, and does not induce or inhibit enzymes of the cytochrome P450 system. No clinically significant drug–drug interactions have been discovered as yet. Experimental data suggest anticonvulsant as well as analgesic effects. Large clinical studies have demonstrated its efficacy for treatment of patients with partial seizures. LCM is well tolerated, and the most common adverse events are unspecific central nervous system and gastrointestinal effects such as dizziness, vertigo, nausea, and headache. LCM is approved for treatment of partial seizures with or without secondary generalization in the United States and the European Union within a dose range of 200 to 400 mg per day, administered twice daily. In addition to the oral formulations, an intravenous infusion solution is available.Keywords: lacosamide, epilepsy, antiepileptic drug

  12. [Pharmacological effects of hordenine].

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    Hapke, H J; Strathmann, W

    1995-06-01

    Hordenine is an ingredient of some plants which are used as feed for animals, i.e. in sprouting barley. After ingestion of such feed hordenine may be detected in blood or urine of horses which in case of racing horses may be the facts of using prohibited compounds. Results of some experiments in pharmacological models show that hordenine is an indirectly acting adrenergic drug. It liberates norepinephrine from stores. In isolated organs and those structures with reduced epinephrine contents the hordenine-effect is only very poor. Experiments in intact animals (rats, dogs) show that hordenine has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood flow volume, inhibits gut movements but has no effect upon the psychomotorical behaviour of mice. All effects are short and only possible after high doses which are not to be expected after ingestion of hordenine containing feed for horses. A measurable increase of the performance of racing horses is quite improbable.

  13. Synthesis of 14-Alkoxymorphinan Derivatives and Their Pharmacological Actions

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    Schmidhammer, Helmut; Spetea, Mariana

    Among opioids, morphinans play an important role as therapeutically valuable drugs. They include pain relieving agents such as naturally occurring alkaloids (e.g. morphine, codeine), semisynthetic derivatives (e.g. oxycodone, oxymorphone, buprenorphine), and synthetic analogs (e.g. levorphanol). Currently used opioid analgesics also share a number of severe side effects, limiting their clinical usefulness. The antagonist morphinans, naloxone and naltrexone are used to treat opioid overdose, opioid dependence, and alcoholism. All these opioid drugs produce their biological actions through three receptor types, µ, δ, and κ, belonging to the G-protein-coupled receptor family. Considerable effort has been put forward to understand the appropriate use of opioid analgesics, while medicinal chemistry and opioid pharmacology have been continuously engaged in the search for safer, more efficacious and nonaddicting opioid compounds, with the final goal to reduce complications and to improve patient compliance. Toward this goal, recent advances in chemistry, ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter. Current developments of different structural patterns of 14-alkoxymorphinans as research tools and their potential therapeutic opportunities are also summarized.

  14. [Advance on pharmacologic actions, toxicity and pharmacokinetics of pyrrolizidine alkaloids].

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    Gao, Jiangguo; Wang, Changhong; Li, Yan; Wang, Zhengtao

    2009-03-01

    Plants containing pyrrolizidine alkaloids were widely used in traditional medicine. Its hepatotoxicity is main toxicity as well known internationally. In order to providing some foundation for the future studies, the advancement on the pharmacologic actions, toxicity, and pharmacokinetics or toxicokinetics of pyrrolizidine alkaloids was reviewed.

  15. [The processing of Gekko gecko and the pharmacological action of its different parts].

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    Gong, Q; Yu, R; Wang, W; Zhang, D; Den, S; Dai J

    1998-04-01

    Both pharmacologic and toxic experiments are made on different parts of Gekko gecko Linnaeus. The results show that Gekko gecko Linnaeus' heads and its feet have obvious pharmacological action without any toxic or side effects, which provides a sound basis for the increase in its clinical utilization and the expansion of its medicinal parts as well as guarantee of safety and effectiveness after taking the medicine.

  16. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives.

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    Qian, Jia-Qing

    2002-12-01

    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.

  17. CURCUMIN- PHARMACOLOGICAL ACTIONS AND ITS ROLE IN DENTISTRY

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    SHARMILA DEVI DEVARAJ, PRASANNA NEELAKANTAN

    2014-05-01

    Full Text Available Turmeric (Curcuma longa is an ancient dye, flavouring and medical herb, widely used in Asian countries. It is a herb that has been widely used in Indian medicine, cookery, and cosmetics. The main component of turmeric is curcumin. Curcumin has a surprisingly wide range of beneficial properties includes anti inflammatory, antioxidant, chemopreventive, chemotherapeutic activity etc.  The activity of curcumin derived from its complex chemistry as well as its ability to influence the multiple signalling pathways. This review article is to highlight the pharmacological action and its therapeutic role in dentistry.   

  18. Pharmacological Effects of Niacin on Acute Hyperlipemia.

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    la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-01-01

    The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

  19. The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides.

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    Ming, Xin; Carver, Kyle; Fisher, Michael; Noel, Romain; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien; Cao, Canhong; Bauman, John; Juliano, Rudolph L

    2013-04-01

    The attainment of strong pharmacological effects with oligonucleotides is hampered by inefficient access of these molecules to their sites of action in the cytosol or nucleus. Attempts to address this problem with lipid or polymeric delivery systems have been only partially successful. Here, we describe a novel alternative approach involving the use of a non-toxic small molecule to enhance the pharmacological effects of oligonucleotides. The compound Retro-1 was discovered in a screen for small molecules that reduce the actions of bacterial toxins and has been shown to block the retrograde trafficking pathway. We demonstrate that Retro-1 can also substantially enhance the effectiveness of antisense and splice switching oligonucleotides in cell culture. This effect occurs at the level of intracellular trafficking or processing and is correlated with increased oligonucleotide accumulation in the nucleus but does not involve the perturbation of lysosomal compartments. We also show that Retro-1 can alter the effectiveness of splice switching oligonucleotides in the in vivo setting. These observations indicate that it is possible to enhance the pharmacological actions of oligonucleotides using non-toxic and non-lysosomotropic small molecule adjuncts.

  20. Overview of pharmacological action and toxic effects of Piper Longum%荜茇的药理作用与毒性作用研究概述

    Institute of Scientific and Technical Information of China (English)

    乔佛晓; 禹玉洪; 李燕

    2015-01-01

    Chinese herbal medicine is used more and more in human health, due to fewer adverse reactions. Thousands of plants have been used traditionally to treat various diseases. Among them, plants in Pipraceae play an important role in the treatment of many human diseases. Piper longum L. ,as a tradi-tional Chinese herbal medicine, so far has been used for the treatment of various diseases such as:cancer, protecting liver, anti-oxidant, anti-inflammatory and immune regulation, dilating the coronary vessels, anti-bacterial, anti-platelet, anti-hyperlipidemic, relieving pain, insecticidal, protecting radiation, inhibiting melanin generation, protecting myocardial, anti-depression, anti-fungal, anti-amiba and other pharmaco-logical effect. Piper longum L. and its main active components piperine and piperlonguminine have better safety. This study provides detailed information about the Piper longum L. , including phytochemistry, pharmacological profile and safety profile. In view of the commercial, economic, and medicinal importance of the Piper longum L. , it is useful for researchers to study the plant in detail.%由于不良反应较少,中草药在人类健康中的应用越来越多。用于治疗各种疾病的传统中草药数以万计。在这些中草药中,胡椒科植物在治疗人类多种疾病中具有重要作用。荜茇作为传统中草药至今还用于治疗各类疾病如:抗癌、保肝、抗氧化、抗炎、免疫调节、扩张冠状动脉血管、抗菌、抗血小板、抗生育、抗高血脂、减肥、止痛、杀虫、辐射防护、抑制黑色素生成、保护心肌、抗抑郁、抗真菌、抗阿米巴等药理学作用。荜茇及主要有效成分胡椒碱、荜茇环碱和荜茇宁的安全性较好。本文主要综述荜茇的植物化学、药理学作用及安全性方面的研究进展。由于荜茇具有中药的商业、经济及药用价值,对荜茇的详细研究非常有意义。

  1. Systems Pharmacology: Network Analysis to Identify Multiscale Mechanisms of Drug Action

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    Zhao, Shan; Iyengar, Ravi

    2013-01-01

    Systems approaches have long been used in pharmacology to understand drug action at the organ and organismal levels. The application of computational and experimental systems biology approaches to pharmacology allows us to expand the definition of systems pharmacology to include network analyses at multiple scales of biological organization and to explain both therapeutic and adverse effects of drugs. Systems pharmacology analyses rely on experimental “omics” technologies that are capable of measuring changes in large numbers of variables, often at a genome-wide level, to build networks for analyzing drug action. A major use of omics technologies is to relate the genomic status of an individual to the therapeutic efficacy of a drug of interest. Combining pathway and network analyses, pharmacokinetic and pharmacodynamic models, and a knowledge of polymorphisms in the genome will enable the development of predictive models of therapeutic efficacy. Network analyses based on publicly available databases such as the U.S. Food and Drug Administration’s Adverse Event Reporting System allow us to develop an initial understanding of the context within which molecular-level drug-target interactions can lead to distal effectors in a process that results in adverse phenotypes at the organ and organismal levels. The current state of systems pharmacology allows us to formulate a set of questions that could drive future research in the field. The long-term goal of such research is to develop polypharmacology for complex diseases and predict therapeutic efficacy and adverse event risk for individuals prior to commencement of therapy. PMID:22235860

  2. Pharmacological effects of lavandulifolioside from Leonurus cardiaca.

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    Miłkowska-Leyck, Katarzyna; Filipek, Barbara; Strzelecka, Halina

    2002-04-01

    Lavandulifolioside was detected for the first time in Leonurus cardiaca var. vulgaris [Moench] Briquet (Lamiaceae). The isolation was performed from the butanolic extract of the aerial parts and the identification by NMR and MS. The pharmacological properties of lavandulifolioside consist of significant negative chronotropism, prolongation of the P-Q, Q-T intervals and QRS complex, and decrease of blood pressure. Contrary to the butanolic extract lavandulifolioside did not reduce the spontaneous locomotor activity. In conclusion, the pharmacological pattern of lavandulifolioside did not explain the pharmacological effects of L. cardiaca L. alone.

  3. Vanadium compounds biological actions and potential as pharmacological agents.

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    Tsiani, E; Fantus, I G

    1997-03-01

    Vanadium is an element found in low concentrations in mammals, for which a function remains to be discovered. Over the past century, vanadium compounds have been suggested anecdotally as therapeutic agents for a variety of diseases. The discovery that vanadate inhibits various enzymes, in particular protein tyrosine phosphatases, and mimics many of the biological actions of insulin suggested a potential role in the therapy of diabetes mellitus. Successful use and an enhancement of insulin sensitivity in rodents and human diabetic subjects, as well as the finding that these agents are capable of stimulating metabolic effects while bypassing the insulin receptor and the early steps in insulin action, target these agents preferentially toward type II diabetes mellitus. Long-term safety remains a major concern, as tissue accumulation and relative nonspecificity of enzyme inhibition may result in adverse effects. Continued research into mechanism of action, consequences of chronic administration, and improvement of specificity is warranted. Regardless of their ultimate success or failure as therapeutic agents, vanadium compounds continue to be useful probes of enzyme structure and function in various biological processes. (Trends Endocrinol Metab 1997;8:51-58). (c) 1997, Elsevier Science Inc.

  4. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.

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    Panossian, Alexander

    2017-08-01

    Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of

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

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    Eison, A S; Temple, D L

    1986-03-31

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

  6. Pharmacological Treatment Effects on Eye Movement Control

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    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

    2008-01-01

    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  7. 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

  8. Pharmacological actions and acute toxicity of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones.

    Science.gov (United States)

    Singh, G B; Leach, G D; Atal, C K

    1987-06-01

    Some pharmacological actions and acute toxicity effects of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones have been described in experimental animals. The compounds antagonised the contractions evoked by a variety of agonists on several smooth muscle preparations in vitro. They produced inhibitory effects on spontaneously contracting uteri from pregnant rats and relaxant effects on pendular movements of rabbit duodenum and on dog intestinal movements in vivo. The compounds inhibited the castor oil induced diarrhoea in rat and propulsion of charcoal test meal in mice. Phenylbutazone showed similar effect on castor oil diarrhoea. The compounds failed to modify gestation period or parturition in pregnant rats. They antagonised bradykinin-induced bronchospasm in guinea pig. The compounds showed no significant effect on cardiovascular and respiratory systems: CNS and general behaviour were not affected even at high doses. Oral LD50 for both the compounds was greater than 2 g/kg.

  9. A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

    Directory of Open Access Journals (Sweden)

    Hao Sun

    2016-08-01

    Full Text Available AbstractRhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.

  10. A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient.

    Science.gov (United States)

    Sun, Hao; Luo, Guangwen; Chen, Dahui; Xiang, Zheng

    2016-01-01

    Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.

  11. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology

    Science.gov (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

    2016-01-01

    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1 receptors. PMID:27886063

  12. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

    Science.gov (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

    2016-11-23

    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

  13. Pharmacology of new oral anticoagulants: mechanism of action, pharmacokinetics, pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2013-12-01

    Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.

  14. Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

    Science.gov (United States)

    Houts, Arthur C.; And Others

    1994-01-01

    Assesses overall effectiveness of psychological and pharmacological treatments, relative effectiveness of specific treatments, and moderators of treatment effectiveness for nocturnal enuretic children via quantitative integration of research. Findings confirm that more children benefit from psychological than from pharmacological interventions and…

  15. Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

    Institute of Scientific and Technical Information of China (English)

    Wen-yu WU; Yi-ping WANG

    2012-01-01

    Salvia miltiorrhiza,a traditional medical herb known as danshen,has been widely used in China to improve blood circulation,relieve blood stasis,and treat coronary heart disease.S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs,rosmarinic acid (RA) and lithospermic acid (LA),as active components.The drug has been used in the clinic to improve blood circulation and treat coronary heart disease.The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated.Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities,especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury.Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system.This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt,based on published works and our own observations.

  16. Oleuropein in olive and its pharmacological effects.

    Science.gov (United States)

    Omar, Syed Haris

    2010-01-01

    Olive from Olea europaea is native to the Mediterranean region and, both the oil and the fruit are some of the main components of the Mediterranean diet. The main active constituents of olive oil include oleic acid, phenolic constituents, and squalene. The main phenolic compounds, hydroxytyrosol and oleuropein, give extra-virgin olive oil its bitter, pungent taste. The present review focuses on recent works that have analyzed the relationship between the major phenolic compound oleuropein and its pharmacological activities including antioxidant, anti-inflammatory, anti-atherogenic, anti-cancer activities, antimicrobial activity, antiviral activity, hypolipidemic and hypoglycemic effect.

  17. [Mechanisms of action, pharmacology and interactions of dolutegravir].

    Science.gov (United States)

    Ribera, Esteban; Podzamczer, Daniel

    2015-03-01

    Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI), whose potential and binding half-life in the integrase are far superior to those of raltegravir and elvitegravir, conferring it with unique characteristics in terms of its genetic barrier to resistance and activity against viruses with one or more mutations in the integrase. The pharmacokinetic properties of dolutegravir allow once-daily dosing (50 mg), with or without food, maintaining concentrations far above those effective against wild-type viruses. If integrase resistance mutations are present, the recommended dosing regimen is 50 mg/12 h. The distribution of dolutegravir in cerebrospinal fluid is good and effective concentrations are also reached in the male and female genital tracts. Dolutegravir is metabolized by UGT1A1 and, to a lesser extent, by CYP3A4, without being an inducer or inhibitor of the usual metabolic systems. It has a very low potential for drug interactions and can be administered in routine doses with most drugs. Dose adjustment is not required, even in patients with renal insufficiency or mild or moderate liver failure. Increasing the dose of dolutegravir (50 mg/12 h) is only recommended when administered with efavirenz, nevirapine, fosamprenavir/r, tipranavir/r, rifampicin, carbamazepine, phenytoin and phenobarbital. Coadministration of dolutegravir with etravirine is not recommended without a protease inhibitor or with Hypericum perforatum. Dolutegravir should be administered 2 h before or 6 h after antacids or products with polyvalent cations. Dolutegravir can reduce renal tubule secretion of substances excreted via OCT2, with a slight initial increase in creatinine, with no risk of renal toxicity. The drug can also increase metformin concentrations and consequently monitoring is recommended in case dose adjustment is required. In summary, dolutegravir has excellent pharmacokinetic and drug interaction profiles. Copyright © 2015 Elsevier España, S

  18. Pharmacological actions of Thespesia populnea relevant to Alzheimer's disease.

    Science.gov (United States)

    Vasudevan, M; Parle, M

    2006-11-01

    Thespesia populnea (Malvaceae) is a large tree found in the tropical regions and coastal forests of India. Various parts of T. populnea are found to possess useful medicinal properties, such as antifertility, antibacterial, anti-inflammatory, antioxidant, purgative and hepatoprotective activity. The present study was undertaken to investigate the effects of T. populnea bark on cognitive functions, total cholesterol levels and cholinesterase activity in mice. A total of 312 mice divided into 52 different groups were employed in the present investigation. The ethanolic extract of T. populnea (TPE) was administered orally in three doses (100, 200 and 400 mg/kg) for 7 successive days to different groups of young and aged mice. The learning and memory parameters were assessed using elevated plus maze and passive avoidance apparatus. TPE (200 and 400 mg/kg, p.o.) showed significant improvement in memory of young and aged mice. TPE also reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Furthermore, TPE reduced significantly the central (brain) cholinesterase activity in mice. TPE exhibited a remarkable cholesterol lowering property comparable to simvastatin (a standard drug) in the present study. Furthermore, we observed that, T. populnea bark possessed a powerful memory enhancing activity in mice. Since diminished cholinergic transmission and increased cholesterol levels appear to be responsible for development of amyloid plaques and dementia in Alzheimer patients, TPE may prove to be a useful medicine on account of its multifarious beneficial effects, such as memory improving property, cholesterol lowering, anticholinesterase and anti-inflammatory activity. Therefore, T. populnea bark appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patients.

  19. Systems pharmacology dissection of multi-scale mechanisms of action for herbal medicines in stroke treatment and prevention.

    Directory of Open Access Journals (Sweden)

    Jingxiao Zhang

    Full Text Available Annually, tens of millions of first-ever strokes occur in the world; however, currently there is lack of effective and widely applicable pharmacological treatments for stroke patients. Herbal medicines, characterized as multi-constituent, multi-target and multi-effect, have been acknowledged with conspicuous effects in treating stroke, and attract extensive interest of researchers although the mechanism of action is yet unclear. In this work, we introduce an innovative systems-pharmacology method that combines pharmacokinetic prescreening, target fishing and network analysis to decipher the mechanisms of action of 10 herbal medicines like Salvia miltiorrhizae, Ginkgo biloba and Ephedrae herba which are efficient in stroke treatment and prevention. Our systematic analysis results display that, in these anti-stroke herbal medicines, 168 out of 1285 constituents with the favorable pharmacokinetic profiles might be implicated in stroke therapy, and the systematic use of these compounds probably acts through multiple mechanisms to synergistically benefit patients with stroke, which can roughly be classified as preventing ischemic inflammatory response, scavenging free radicals and inhibiting neuronal apoptosis against ischemic cerebral damage, as well as exhibiting lipid-lowering, anti-diabetic, anti-thrombotic and antiplatelet effects to decrease recurrent strokes. Relying on systems biology-based analysis, we speculate that herbal medicines, being characterized as the classical combination therapies, might be not only engaged in multiple mechanisms of action to synergistically improve the stroke outcomes, but also might be participated in reducing the risk factors for recurrent strokes.

  20. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.

    Science.gov (United States)

    Shen, Hong-Wu; Jiang, Xi-Ling; Winter, Jerrold C; Yu, Ai-Ming

    2010-10-01

    5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.

  1. 丹参成分及其药理作用%Composition and Pharmacological Action of Salvia Miltiorrhizas Bge

    Institute of Scientific and Technical Information of China (English)

    董凤彩

    2015-01-01

    Danshen ingredients are water-soluble and fat soluble two,its pharmacological effectsare different focus,have important effects on the cardiovascular,digestive system,nervous system.Because of the pharmacological action of Radix Salviae Miltiorrhizae is relatively stable,can be widely used in clinical.This paper makes an in-depth analysisfor the components in Salvia miltiorrhiza and its pharmacological effects,and provide an important reference for clinical application.%丹参成分主要有水溶性及脂溶性2种,其药理作用不同各有侧重,对心血管系统、消化系统、中枢神经系统都具有重要影响。因丹参的药理作用比较稳定,可在临床治疗中广泛应用。本文针对丹参成分及其药理作用进行深入分析,为临床应用提供重要参考。

  2. Measuring the effectiveness of pharmacology teaching in undergraduate medical students.

    Science.gov (United States)

    Urrutia-Aguilar, Maria Esther; Martinez-Gonzalez, Adrian; Rodriguez, Rodolfo

    2012-03-01

    Information overload and recent curricular changes are viewed as important contributory factors to insufficient pharmacological education of medical students. This study was designed to assess the effectiveness of pharmacology teaching in our medical school. The study subjects were 455 second-year medical students, class of 2010, and 26 pharmacology teachers at the National University of Mexico Medical School. To assess pharmacological knowledge, students were required to take 3 multiple-choice exams (70 questions each) as part of their evaluation in the pharmacology course. A 30-item questionnaire was used to explore the students' opinion on teaching. Pharmacology professors evaluated themselves using a similar questionnaire. Students and teachers rated each statement on a 5-point Likert scale. The groups' exam scores ranged from 54.5% to 90.0% of correct responses, with a mean score of 77.3%. Only 73 (16%) of 455 students obtained an exam score of 90% and higher. Students' evaluations of faculty and professor self-ratings were very high (90% and 96.2%, of the maximal response, respectively). Student and professor ratings were not correlated with exam scores (r = 0.291). Our study shows that knowledge on pharmacology is incomplete in a large proportion of second-year medical students and indicates that there is an urgent need to review undergraduate training in pharmacology. The lack of relationship between the subjective ratings of teacher effectiveness and objective exam scores suggests the use of more demanding measures to assess the effectiveness of teaching.

  3. The experimental study of the specific pharmacological action of «Artproment» combined gel

    Directory of Open Access Journals (Sweden)

    О. S. Shpychak

    2014-08-01

    Full Text Available The preclinical experimental research concerning the study of the specific pharmacological action of "ArtpromentÒ" gel has been done. The gel developed contains propolis phenolic hydrophobic drug, articaine hydrochloride, menthol and rosemary oil in its composition. The medicine is planned to application in sports medicine with the purpose of treating traumatic injuries of organs of the locomotor apparatus accompanied with sport traumas (bruises, dislocations, sprains, ruptures of ligaments, tendons, etc.. In this work the pharmacological, physiological, instrumental methods of research and methods of mathematical statistics have been used. The study of the analgesic and local anesthetic action of the gel developed was conducted at the premises of the Central Research Laboratory of NUPh under the supervision of Doctor of Pharmacy, professor L.V.Iakovlieva on the model of tail thermoirritation in white rats weighing 180.0-200.0 g. The analgesic and local anesthetic actions were estimated by the ability of the medicine studied to change the pain threshold (duration of the latent period, sеc. in animals of the test group comparing to the control group in the dose of 25 mg/cm2 and the base in the dose of 30 mg/cm2 after application to the tail. The results of the experiment testify that when studying the influence of the combined gel on the course of the experimental nociceptive response of the central origin the significant analgesic action of "ArtpromentÒ" medicine has been determined; its highest intensity was observed in 2.5 and 3.5 hours after application and is 52 % and 59 %, respectively. Despite the fact that the progress of the pain syndrome in the model of tail thermoirritation is mediated by the central nervous system, it is possible to conclude that the developed gel has an expressed analgesic and local anesthetic action. The medicine shows the significant anti-edema action at the level of the reference medicine "Diclofen-gel" on the

  4. A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

    OpenAIRE

    Hao Sun; Guangwen Luo; Dahui Chen; Zheng Xiang

    2016-01-01

    AbstractRhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few foc...

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

    Science.gov (United States)

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

    2012-12-01

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

  6. PHARMACOLOGICAL EFFECTS OF CAROTENOIDS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Sumita S. Kadia

    2012-01-01

    Full Text Available Vitamin A is an essential vitamin which is required in the vision process, epithelial maintenance, mucous secretion and reproduction obtained from carotenoids. Carotenoids have been considered to provide benefits in age-related diseases, against some forms of cancer (in especial lung cancer, strokes, macular degeneration, and cataracts. Till date, more than 600 carotenoids are known and 50 of them are consumed in meals to be transformed into the essential nutrient vitamin A. After their absorption, these carotenoids are metabolized by an oxidative rupture to retinal, retinoic acid and small quantities of breakdown products and are transported by plasma lipoproteins. Carotenes are mainly associated with low-density lipoproteins, while xanthophylls show a uniform distribution between the low- and high-density lipoproteins. The present review provides an insight into the recent status of pharmacological aspects of carotenoids.

  7. [Study on characteristics of pharmacological effects of traditional Chinese medicines distributing along stomach meridian based on medicinal property combination].

    Science.gov (United States)

    Zhang, Bai-Xia; Gu, Hao; Guo, Hong-Ling; Ma, Li; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    and provide a new way of thinking and method for revealing the mechanism action of TCMs distributing in the stomach meridian and discovering the pharmacological effects of TCMs distributing in the stomach meridian.

  8. Evidence from pharmacology and pathophysiology suggests that chemicals with dissimilar mechanisms of action could be of bigger concern in the toxicological risk assessment of chemical mixtures than chemicals with a similar mechanism of action

    DEFF Research Database (Denmark)

    Hadrup, Niels

    2014-01-01

    mechanisms of action, similar modes of action or with common target organs. In the European Union, efforts are currently being made to subgroup chemicals according to this need. However, it remains to be determined whether this is the best strategy to obtain data for risk assessment. In conditions...... such as cancer or HIV, it is generally recognised that pharmacological combination therapy targeting different mechanisms of action is more effective than a strategy where only one mechanism is targeted. Moreover, in diseases such as acute myocardial infarction and congestive heart failure, several organ systems...

  9. Bioactive Compounds of Aristotelia chilensis Stuntz and their Pharmacological Effects.

    Science.gov (United States)

    Romanucci, Valeria; D'Alonzo, Daniele; Guaragna, Annalisa; Di Marino, Cinzia; Davinelli, Sergio; Scapagnini, Giovanni; Di Fabio, Giovanni; Zarrelli, Armando

    2016-01-01

    Aristotelia chilensis ([Molina], Stuntz) a member of the family Eleocarpaceae, is a plant native to Chile that is distributed in tropical and temperate Asia, Australia, the Pacific Area, and South America. The juice of its berries has important medicinal properties, as an astringent, tonic, and antidiarrhoeal. Its many qualities make the maqui berry the undisputed sovereign of the family of so-called "superfruits", as well as a valuable tool to combat cellular inflammation of bones and joints. Recently, it is discovered that the leaves of the maqui berry have important antibacterial and antitumour activities. This review provides a comprehensive overview of the traditional use, phytochemistry, and biological activity of A. chilensis using information collected from scientific journals, books, and electronic searches. Anthocyanins, other flavonoids, alkaloids, cinnamic acid derivatives, benzoic acid derivatives, other bioactive molecules, and mineral elements are summarized. A broad range of activities of plant extracts and fractions are presented, including antioxidant activity, inhibition of visible light-induced damage of photoreceptor cells, inhibition of α-glucosidase, inhibition of pancreatic lipase, anti-diabetic effects, anti-inflammatory effects, analgesic effects, anti-diabetes, effective prevention of atherosclerosis, promotion of hair growth, anti-photo ageing of the skin, and inhibition of lipid peroxidation. Although some ethnobotanical uses have been supported in in vitro experiments, further studies of the individual compounds or chemical classes of compounds responsible for the pharmacological effects and the mechanisms of action are necessary. In addition, the toxicity and the side effects from the use of A. chilensis, as well as clinical trials, require attention.

  10. (-)-Carvone: antispasmodic effect and mode of action.

    Science.gov (United States)

    Souza, Fábia Valéria M; da Rocha, Marcelly Barbosa; de Souza, Damião P; Marçal, Rosilene Moretti

    2013-03-01

    (-)-Carvone is a monoterpene ketone found in spearmint (Mentha spicata var. crispa) essential oil that is widely used as an odor and flavor additive. An intestinal antispasmodic effect was recently reported for (-)-carvone, and it has been shown to be more potent than its (+)-antipode. The mechanism of (-)-carvone action in the intestines has not been investigated. To gain a better understanding of the (-)-carvone antispasmodic effect, we investigated its pharmacological effects in the guinea pig ileum. Terminal portions of the ileum were mounted for isotonic contraction recordings. The effect of (-)-carvone was compared with that of the classical calcium channel blocker (CCB) verapamil. In isolated ileal smooth muscle, (-)-carvone did not produce direct contractile or relaxation responses and did not modify electrically elicited contractions or low K(+)-evoked contractions. The submaximal contractions induced by histamine (p<0.001), BaCl2 (p<0.05), and carbachol (p<0.01) were significantly reduced by (-)-carvone. The contractile response elicited by high concentrations of carbachol was reduced but not abolished by (-)-carvone. No additive action was detected with co-incubation of (-)-carvone and verapamil on carbachol-induced contraction. (-)-Carvone reduced the contraction induced by high K(+) and was almost 100 times more potent than verapamil. Thus, (-)-carvone showed a typical and potent CCB-like action. Many effects described for both (-)-carvone and spearmint oil can be explained as a CCB-like mode of action.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Intracellular Signaling Mechanisms Pharmacological Action of Jasminum amplexicaule Buch.-Ham. (Oleaceae) on Gastrointestinal Secretion.

    Science.gov (United States)

    Gao, Zhenhua; Yin, Junqiang; Xie, Xiaolin; Long, Hanwu; Qi, Xiang; Lin, Changhu; Wu, Liangcai

    2014-01-01

    Jasminum amplexicaule Buch-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule (JME) was examined for pharmacology on human colonic epithelial cell line T84 by the short-circuit current technique. The results showed that pretreatment of T84 cells with JME produced a concentration-dependent (0-1000 μg/mL. EC50 = 0.055 mg/ mL) inhibition effect on adrenalin (Adr.)-induced Cl- secretion. The maximal response was observed at 200 μg/mL. It has been demonstrated that JME has a direct effect on the enterocyte. Our results also demonstrated that the JME exerted inhibitory effect on gastrointestinal Cl(-)secretion that effected by acting on basolateral β-adrenoreceptors. These results suggested that the Chinese traditional medicine of JME can be used for the treatment of acute diarrhea and bellyache.

  13. Action-Specific Effects Underwater

    OpenAIRE

    Witt, Jessica; Schuck, Donald M; Taylor, J. Eric T.

    2011-01-01

    Action-specific effects on perception are apparent in terrestrial environments. For example, targets that require more effort to walk, jump, or throw to look farther away than when the targets require less effort. Here, we examined whether action-specific effects would generalize to an underwater environment. Instead, perception might be geometrically precise, rather than action-specific, in an environment that is novel from an evolutionary perspective. We manipulated ease to swim by giving p...

  14. Network Pharmacology Studies on the Bioactive Compounds and Action Mechanisms of Natural Products for the Treatment of Diabetes Mellitus: A Review

    Science.gov (United States)

    Li, Weiwei; Yuan, Guoqi; Pan, Yuxiang; Wang, Cong; Chen, Haixia

    2017-01-01

    Diabetes mellitus (DM) is a kind of chronic and metabolic disease, which can cause a number of diseases and severe complications. Network pharmacology approach is introduced to study DM, which can combine the drugs, target proteins and disease and form drug-target-disease networks. Network pharmacology has been widely used in the studies of the bioactive compounds and action mechanisms of natural products for the treatment of DM due to the multi-components, multi-targets, and lower side effects. This review provides a balanced and comprehensive summary on network pharmacology from current studies, highlighting different bioactive constituents, related databases and applications in the investigations on the treatment of DM especially type 2. The mechanisms related to type 2 DM, including α-amylase and α-glucosidase inhibitory, targeting β cell dysfunction, AMPK signal pathway and PI3K/Akt signal pathway are summarized and critiqued. It suggests that the network pharmacology approach cannot only provide a new research paradigm for natural products, but also improve the current antidiabetic drug discovery strategies. Furthermore, we put forward the perspectives on the reasonable applications of network pharmacology for the therapy of DM and related drug discovery.

  15. Network Pharmacology Studies on the Bioactive Compounds and Action Mechanisms of Natural Products for the Treatment of Diabetes Mellitus: A Review.

    Science.gov (United States)

    Li, Weiwei; Yuan, Guoqi; Pan, Yuxiang; Wang, Cong; Chen, Haixia

    2017-01-01

    Diabetes mellitus (DM) is a kind of chronic and metabolic disease, which can cause a number of diseases and severe complications. Network pharmacology approach is introduced to study DM, which can combine the drugs, target proteins and disease and form drug-target-disease networks. Network pharmacology has been widely used in the studies of the bioactive compounds and action mechanisms of natural products for the treatment of DM due to the multi-components, multi-targets, and lower side effects. This review provides a balanced and comprehensive summary on network pharmacology from current studies, highlighting different bioactive constituents, related databases and applications in the investigations on the treatment of DM especially type 2. The mechanisms related to type 2 DM, including α-amylase and α-glucosidase inhibitory, targeting β cell dysfunction, AMPK signal pathway and PI3K/Akt signal pathway are summarized and critiqued. It suggests that the network pharmacology approach cannot only provide a new research paradigm for natural products, but also improve the current antidiabetic drug discovery strategies. Furthermore, we put forward the perspectives on the reasonable applications of network pharmacology for the therapy of DM and related drug discovery.

  16. Pharmacological efficacy of CPU 86017 on hypoxic pulmonary hypertension in rats: mediated by direct inhibition of calcium channels and antioxidant action, but indirect effects on the ET-1 pathway.

    Science.gov (United States)

    Zhang, Tian-Tai; Cui, Bing; Dai, De-Zai; Tang, Xiao-Yun

    2005-12-01

    Endothelin-1 (ET-1) plays a key role in the pathogenesis of pulmonary hypertension. The present study was conducted to examine the effects of a novel compound p-chlorobenzyltetrahydroberberine (CPU 86017) on endothelin-1 system of hypoxia-induced pulmonary hypertension in rats. SD male rats were divided into control, untreated pulmonary hypertension, nifedipine (10 mg/kg p.o.), and CPU 86017 (80, 40, and 20 mg/kg p.o.) groups. The pulmonary hypertension was established by housing the rats in a hypoxic (10 +/- 0.5% oxygen) chamber 8 hours per day for 4 weeks. Hemodynamic and morphologic assessment exhibited a significant increase in the central vein pressure (CVP), right ventricular systolic pressure (RVSP), and pulmonary arteriole remodeling in the pulmonary hypertensive rats, which were improved by CPU 86017 80 and 40 mg/kg administration (P CPU 86017 groups. The maladjustment of redox enzyme system in pulmonary hypertension rats was corrected after treatment. We concluded that CPU 86017 improves pulmonary hypertension mainly to suppress the endothelin-1 pathway at the upstream and downstream via calcium antagonism and antioxidative action, then, resulting in a relief in pathogenesis of the disease.

  17. Pharmacological effects of strictosamide on Charles River mice

    OpenAIRE

    Morais,Júlio; Candeias, Fátima; Pereira, António; Abreu, Pedro

    2002-01-01

    In previous publications we reported the isolation of indole alkaloids from the stem bark and roots of Sarcocephalus latifolius (Smith) Bruce (Nauclea latifolia Sm.)(Rubiaceae) collected in Guinea-Bissau, as well as antiplasmodial activity of its main constituent, strictosamide, wich accounts for 11% of the total ethanol extract. In this communication we present the pharmacological effects os strictosamide on Charles River mice.

  18. 护理药理学教学改革探讨%Pharmacological action and clinical

    Institute of Scientific and Technical Information of China (English)

    覃梦岚

    2015-01-01

    Through finding the problems encountered in nursing pharmacology teaching, from rational use of materials, training of teachers team, teaching skills and memory, enrich the teaching means, to achieve the goal of emotion etc. five aspects put forward and to explore the effective methods of teaching reform, provides the reference for other teachers.%文章通过寻找护理药理学教学中遇到的问题,从合理使用教材、培养师资团队、传授技巧记忆、充实教学手段、实现情感目标等5个方面提出和探讨行之有效的教学改革方法,为其他教师提供参考。

  19. Carum copticum L.: A Herbal Medicine with Various Pharmacological Effects

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Boskabady

    2014-01-01

    Full Text Available Carum copticum L. commonly known as “Ajwain” is cultivated in many regions of the world including Iran and India, states of Gujarat and Rajasthan. Traditionally, C. copticum has been used in the past for various therapeutic effects including bloating, fatigue, diarrhea, abdominal tumors, abdominal pain, respiratory distress, and loss of appetite. It has other health benefits such as antifungal, antioxidant, antibacterial, antiparasitic, and hypolipidemic effects. This plant contains different important components such as carbohydrates, glucosides, saponins and phenolic compounds (carvacrol, volatile oils (thymol, terpiene, paracymene and beta-pinene, protein, fat, fiber, and minerals including calcium, phosphorus, iron, and nicotinic acid (niacin. In the previous studies, several pharmacological effects were shown for C. copticum. Therefore, in this paper, the pharmacological effects of the plant were reviewed.

  20. Pharmacological effects of two cytolysins isolated from the sea anemone Stichodactyla helianthus

    Indian Academy of Sciences (India)

    T García; D Martinez; A Palmero; C Soto; M Tejuca; F Pazos; R Menéndez; C Alvarez; A Garateix

    2009-12-01

    Sticholysins I and II (St I/II) are cytolysins purified from the sea anemone Stichodactyla helianthus. In this study, we show their pharmacological action on guinea-pig and snail models in native and pH-denatured conditions in order to correlate the pharmacological findings with the pore-forming activity of both isoforms. In guinea-pig erythrocytes ( = 3), St II possessed higher haemolytic activity in comparison with St I and this activity was lost at an alkaline pH. In molluscan central neurons ( = 30), they irreversibly decreased the amplitude of the cholinergic response; St I (EC50 0.6 molL–1) was more potent than St II (EC50 > 6.6 molL–1) and they both increased the duration of the action potential; these effects were absent at an alkaline pH. In guinea-pig isolated atrium ( = 25), both increased the amplitude of the contraction force, but St II was more potent than St I (EC50 0.03 molL–1 and 0.3 molL–1, respectively) and this effect persisted at an alkaline pH. In summary, both cytolysins have neuroactive and cardioactive properties. The main mechanism in molluscan neurons seems to be associated with the cytolytic activity of these molecules, whereas in guinea-pig atrium, the existence of an additional pharmacological mechanism might be contributing to the observed effect.

  1. [Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

    Science.gov (United States)

    Fujimura, H; Tsurumi, K; Yanagihara, M; Hiramatsu, Y; Tamura, Y; Shimizu, Y; Hojo, M; Yoshida, Y; Serizawa, I

    1981-10-01

    The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application.

  2. [Therapeutic action of oral mesoglycan in the pharmacologic treatment of the varicose syndrome and its complications].

    Science.gov (United States)

    Petruzzellis, V; Velon, A

    1985-03-24

    The comparative therapeutic efficacy of mesoglycan and a capillary protective drug derived from rutin was evaluated in a clinical study conducted on a group of patients with varicose syndrome and/or its complications. The clinical assessment of the results obtained was followed by a series of investigations aimed at identifying the action mechanism of the drugs under study. In the experimental model adopted, mesoglycan was found to be well tolerated and effective both in absolute terms and in comparison with the drug used for comparison. Apart from the clinical efficacy of mesoglycan, it was also shown to increase transcutaneous O2 perfusion and blood flow as evidenced by filtrability. On the basis of these results it is suggested that the clinical action and tolerability of mesoglycan make it a valuable aid in the arduous task of treating varicose syndrome and its complications.

  3. Clinical Application and Pharmacological Actions of Ligustrazine Chuanxiong%川芎的药理作用及临床应用

    Institute of Scientific and Technical Information of China (English)

    张文海

    2015-01-01

    目的:研究川芎的药理作用及临床应用。方法收集关于川穹药理作用及临床应用的相关文献,对文献进行总结分析。结果川芎具有活血化瘀、镇静镇痛、抑制氧自由基释放等方面的药理作用。结论川芎在治疗呼吸系统疾病、冠心病、心绞痛、肾病综合征等方面具备比较好的临床疗效。%ObjectiveTo study the pharmacological action and clinical application of Ligusticum chuanxiong. Methods colected the relevant literatures on the pharmacological effects and clinical application of Ligusticum chuanxiong dome, to summarize the literature.Results Ligusticum chuanxiong with pharmacological effects of Huoxue Huayu, sedation and analgesia, inhibit the release of oxygen free radicals.Conclusion Ligusticum chuanxiong in the treatment of respiratory system disease, coronary heart disease, angina pectoris, nephrotic syndrome has better clinical efficacy.

  4. Pills or push-ups? Effectiveness and public perception of pharmacological and non-pharmacological cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Lucius eCaviola

    2015-12-01

    Full Text Available We review work on the effectiveness of different forms of cognitive enhancement, both pharmacological and non-pharmacological. We consider caffeine, methylphenidate, and modafinil for pharmacological cognitive enhancement (PCE and computer training, physical exercise, and sleep for non-pharmacological cognitive enhancement (NPCE. We find that all of the techniques described can produce significant beneficial effects on cognitive performance. However, effect sizes are moderate, and consistently dependent on individual and situational factors as well as the cognitive domain in question. Although meta-analyses allowing a quantitative comparison of effectiveness across techniques are lacking to date, we can conclude that PCE is not more effective than NPCE. We discuss the physiological reasons for this limited effectiveness.We then propose that even though their actual effectiveness seems similar, in the general public PCE is perceived as fundamentally different from NPCE, in terms of effectiveness, but also in terms of acceptability. We illustrate the potential consequences such a misperception of PCE can have.

  5. New aspects in the pharmacology of kindling implications for mechanism of of action in kindling.

    Science.gov (United States)

    Schmidt, J

    1987-01-01

    Kindling is a long-lasting, transsynaptic, pathway-specific plastic change in brain function. It has been proposed as a model of neural plasticity, learning and memory, as well as a model of epilepsy. To elucidate the action of substances characterized by their ability to improve learning and memory and to have an activatory, protective and function restoring effect on nerve cells in distress, the effects of nootropic drugs and of antioxidative acting substances on the development of kindling and the seizure behavior in the kindled state were investigated. Nootropic drugs suppress the development of pentetrazol (PTZ)- and amygdala-kindling and possess anticonvulsive potency preferentially in kindled rats. In comparison to amygdala-kindling the substances were found to be more effective against PTZ-kindled seizures. Chemically different antioxidants in doses known to scavenge free radicals suppress markedly the development of kindling and possess anticonvulsant potency in chemically and electrically kindled rats. The results provide arguments in favor of functional alterations of transmission relevant membrane processes with structural and functional reorganization of membrane constituents and lead to the assumption that the changes mainly in part rest on a selective and focal involvement of free radicals. It is proposed that enhanced calcium entry into neurons and consequent biochemical alterations connected with a focal increase in free radicals is part of the mechanisms underlying kindling phenomenon.

  6. Pharmacological effects of saw palmetto extract in the lower urinary tract

    Institute of Scientific and Technical Information of China (English)

    Mayumi SUZUKI; Yoshihiko ITO; Tomomi FUJINO; Masayuki ABE; Satomi ONOUE; Keizo UMEGAKI; Hiroshi NOGUCHI; Shizuo YAMADA

    2009-01-01

    Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a thera-peutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5α-reductase. Today, α1-adrenoceptor antagonists and muscarinic cholinoceptor antagonists are commonly used in the treatment of men with voiding symptoms secondary to BPH. The improvement of voiding symptoms in patients taking SPE may arise from its binding to pharmacologically rel-evant receptors in the lower urinary tract, such as α1-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine recep-tors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of α1-adrenoceptors in the rat prostate induced by testosterone. Thus, SPE at clinically relevant doses may exert a direct effect on the pharmacological receptors in the lower urinary tract, thereby improving urinary dysfunction in patients with BPH and an overactive bladder. SPE does not have interactions with co-administered drugs or serious adverse events in blood biochemical parameters, suggestive of its relative safety, even with long-term intake. Clinical trials (placebo-controlled and active-controlled trials) of SPE conducted in men with BPH were also reviewed. This review should contribute to the under-standing of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms (LUTS).

  7. Alcohol use disorder: pathophysiology, effects, and pharmacologic options for treatment

    Directory of Open Access Journals (Sweden)

    Wackernah RC

    2014-01-01

    Full Text Available Robin C Wackernah,1 Matthew J Minnick,1 Peter Clapp2 1Department of Pharmacy Practice, 2Department of Pharmaceutical Sciences, School of Pharmacy, Rueckert-Hartman College for Health Professions, Regis University, Denver, CO, USA Abstract: Alcohol use disorders (AUD continue to be a concerning health issue worldwide. Harmful alcohol use leads to 2.5 million deaths annually worldwide. Multiple options exist for the management of dependence on alcohol, not all of which are approved by drug-regulating agencies. Current practice in treating AUD does not reflect the diversity of pharmacologic options that have potential to provide benefit, and guidance for clinicians is limited. Few medications are approved for treatment of AUD, and these have exhibited small and/or inconsistent effects in broad patient populations with diverse drinking patterns. The need for continued research into the treatment of this disease is evident in order to provide patients with more specific and effective options. This review describes the neurobiological mechanisms of AUD that are amenable to treatment and drug therapies that target pathophysiological conditions of AUD to reduce drinking. In addition, current literature on pharmacologic (both approved and non-approved treatment options for AUD offered in the United States and elsewhere are reviewed. The aim is to inform clinicians regarding the options for alcohol abuse treatment, keeping in mind that not all treatments are completely successful in reducing craving or heavy drinking or increasing abstinence. Keywords: abuse, alcohol, alcoholism, craving, dependence, relapse

  8. Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    Science.gov (United States)

    Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2013-01-01

    The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

  9. Pharmacological effects of Salvia miltiorrhiza (Danshen on cerebral infarction

    Directory of Open Access Journals (Sweden)

    Hsieh Ching-Liang

    2010-06-01

    Full Text Available Abstract Danshen, the dried root of Salvia miltiorrhiza, is a Chinese medicine used to promote blood flow and treat vascular disease. The present article reviews the pharmacological effects of Danshen on cerebral infarction and possible interactions between Danshen and Western drugs. Danshen may reduce or prolong the development of atherosclerosis and may have anti-hypertensive and anti-platelet aggregation effects, which prevent cerebral infarction. Danshen may enhance endogenous anti-oxidative enzyme activities such as the expression of endothelial nitric oxide synthase and may scavenge oxygen free radicals. Prevention and treatment of cerebral infarction by Danshen involves multiple pathways, including anti-atherosclerosis, anti-hypertension, anti-platelet aggregation, anti-inflammatory and anti-oxidative effects.

  10. 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.

  11. CNS pharmacology and clinical therapeutic effects of oxiracetam.

    Science.gov (United States)

    Itil, T M; Menon, G N; Songar, A; Itil, K Z

    1986-01-01

    Oxiracetam, a new substance found to be a nootropic in experimental pharmacological studies, was tested in three clinical trials: a single rising dose tolerance and dose-finding study with quantitative pharmaco-electroencephalogram (pharmaco-EEG) and quantitative pharmacopsychology in healthy volunteers; a dose-finding study, at three dose levels for 3 months, with quantitative pharmaco-EEG in mild to moderate dementia patients; and a safety and efficacy study with increasing dosages for 12 weeks with subjective and objective tests in elderly patients with dementia. In single and repeated oral dosages up to 2,400 mg, oxiracetam is a safe compound. According to HZI Data Bank Classification Systems, oxiracetam is a vigilance-enhancing compound with some effects on spontaneous memory. The therapeutic effect of oxiracetam can be discriminated from placebo, and in comparison with piracetam, oxiracetam exhibits greater improvement in memory factor.

  12. 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...

  13. Study on pharmacological action of Xuejieding Tinctures%血竭酊的药理作用研究

    Institute of Scientific and Technical Information of China (English)

    赵永旗; 程洪兵; 张同领; 鲁丽红

    2014-01-01

    Objective To investigate pharmacological action of Xuejieding Tinctures.Methods Anti-inflammation, effects swelling relief, analgesic and acute soft tissue injury disease of Xuejieding Tinctures were determined by mice ear swelling method, rat toe swelling method, hot plate method and freely falling mass damages models, respectively. The experiments were divided into 4 groups, i.e. normal saline control group, positive drug group and Xuejieding Tinctures high and low concentration groups.Results Xuejieding Tinctures containing 40% or 20% crude drug decreased the mice ear swelling (P<0.01);Xuejieding Tinctures also relived rat toe swelling induced by egg white at the end of 6 hours(P<0.01);the pain threshold value of mice were elevated(P<0.01). the acute soft tissue injury in rats were resisted(P<0.01).Conclusion Xuejieding Tinctures has significant anti-inflammation, effects swelling relief, analgesic and can release soft tissue injury.%目的:研究血竭酊的药理作用。方法采用小鼠耳郭肿胀法、大鼠脚趾肿胀法、热板法和自由落体组织损伤模型分别观察其抗炎、消肿、镇痛和抗急性软组织损伤作用。将动物分为模型、阳性药物和血竭酊高、低浓度组。结果与模型组比较,血竭酊高、低浓度组小鼠耳肿胀度显著降低(P<0.01),大鼠蛋清所致脚趾肿胀度6 h显著消除(P<0.01),小鼠痛阈显著提高(P<0.01),明显降低损伤大鼠的表观损伤积分(P<0.01)。结论血竭酊具有显著的抗炎、消肿、止痛及抗急性软组织损伤的作用。

  14. Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines.

    Science.gov (United States)

    Stahl, Stephen M

    2008-12-01

    Numerous "antihistamines" as well as various psychotropic medications with antihistamine properties are widely utilized to treat insomnia. Over-the-counter sleep aids usually contain an antihistamine and various antidepressants and antipsychotics with antihistamine properties have sedative-hypnotic actions. Although widely used for the treatment of insomnia, many agents that block the histamine H1 receptor are also widely considered to have therapeutic limitations, including the development of next-day carryover sedation, as well as problems with chronic use, such as the development of tolerance to sedative-hypnotic actions and weight gain. Although these clinical actions are classically attributed to blockade of the H1 receptor, recent findings with H1 selective agents and H1 selective dosing of older agents are challenging these notions and suggest that some of the clinical limitations of current H1-blocking agents at their currently utilized doses could be attributable to other properties of these drugs, especially to their simultaneous actions on muscarinic, cholinergic, and adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics.

  15. An Inquiry into the Action of Acupuncture on the Human Body by Means of Pharmacology

    Institute of Scientific and Technical Information of China (English)

    LU Yong; WANG Jia-tao

    2009-01-01

    @@ The science of traditional acupuncture was the summary of the law of action of acupuncture made by our predecessors in their long term clinical practice, which plays a very important guiding role in clinic. In order to make the charm of this ancient acupuncture therapy ever lasting, bringing it into line with the modem science and technology is necessary.

  16. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

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

    Science.gov (United States)

    Sáez-Briones, P; Hernández, A

    2013-09-01

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

  18. Study on the pharmacological action and clinical application SanQi%三七的药理作用及其临床应用研究

    Institute of Scientific and Technical Information of China (English)

    钟晓凤

    2015-01-01

    Objective: To discuss the pharmacological action and clinical application of three seven. Methods: Thechemical constituents of three seven analysis, pharmacological action and summarize three seven in chemical composition in clinical application effect. Results:Sanqi can affect the central nervous system, circulatory system, digestive system, urinary system, reproductive system and the immune system and other systems, but also has anti-aging, antitumor and anti-inflammatory effects. Conclusion:as a kind of natural plant medicine,three seven and its extract medicinal extensive effect, less side effect, is worth paying attention to anddeveloped a taste of traditional Chinese medicine.%目的:讨论三七的药理作用及临床应用。方法:对三七的化学成分进行分析,总结三七的药理作用及其在化学成分在临床的应用效果。结果:三七能够对中枢神经系统、循环系统、消化系统、泌尿系统、生殖系统以及免疫系统等系统产生影响,还具有抗衰老、抗肿瘤和抗炎的作用。结论:作为一种天然的植物药,三七及其提取物药用作用广泛,副作用少,是一味值得重视和开发的中药。

  19. The Chemical Constituents and Pharmacological Effects of Bryophyllum calycinum. A review

    Directory of Open Access Journals (Sweden)

    Ali Esmail Al-Snafi

    2014-12-01

    Full Text Available Bryophyllum calycinum belongs to the family crassulaceae was widely used in traditional medicine especially in the tropical areas. The plant contained alkaloids, phenols, flavonoids, tannins, anthocyanins, glycosides, bufadienolides, saponins, coumarins, sitosterols, quinines, carotenoids, tocopherol and lectins . The previous pharmacological studies showed that it exerted many pharmacological effects including anticancer , antioxidant immunomodulating , antibacterial , anthelmentic , antiprotozoal , neurologica ( sedative and anticonvulsant , anti-inflammatory , analgesic , diuresis , antiurolithitic , nephroprotective, hepatoprotective , anti-peptic ulcer , hypotensive , antidiabetic , wound healing and other pharmacological effects. The present review was designed to highlight the chemical constituents and pharmacological effects of Bryophyllum calycinum.

  20. Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.

    Science.gov (United States)

    Vilela, Luciano R; Lima, Isabel V; Kunsch, Érica B; Pinto, Hyorrana Priscila P; de Miranda, Aline S; Vieira, Érica Leandro M; de Oliveira, Antônio Carlos P; Moraes, Marcio Flávio D; Teixeira, Antônio L; Moreira, Fabricio A

    2017-10-01

    Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of tumors on inhaled pharmacologic drugs: I. Flow patterns.

    Science.gov (United States)

    Martonen, T B; Guan, X

    2001-01-01

    Lung carcinomas are now the most common form of cancer. Clinical data suggest that tumors are found preferentially in upper airways, perhaps specifically at carina within bifurcations. The disease can be treated by aerosolized pharmacologic drugs. To enhance their efficacies site-specific drugs must be deposited selectively. Since inhaled particles are transported by air, flow patterns will naturally affect their trajectories. Therefore, in Part I of a systematic investigation, we focused on tumor-induced effects on airstreams, in Part II (the following article [p. 245]), particle trajectories were determined. To facilitate the targeted delivery of inhaled drugs, we simulated bifurcations with tumors on carinas using a commercial computational fluid dynamics (CFD) software package (FIDAP) with a Cray T90 supercomputer and studied effects of tumor sizes and ventilatory parameters on localized flow patterns. Critical tumor sizes existed; e.g., tumors had dominant effects when r/R > or = 0.8 for bifurcation 3-4 and r/R > or = 0.6 for bifurcation 7-8 (r = tumor radius and R = airway radius). The findings suggest that computer modeling is a means to integrate alterations to airway structures caused by diseases into aerosol therapy protocols.

  2. Progress of research on Puerarin pharmacological action%葛根素药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    伟唯; 江培

    2014-01-01

    目的:葛根素是从豆科植物野葛中提取分离出的一种单体,属异黄酮类化合物。葛根素药效明确,药理活性强,药理作用广泛。大量实验研究表明,葛根素具有抗心律失常、抗心肌缺血、扩张血管、改善微循环、降血脂、降血糖、增加脑血流量、抗脑缺血-再灌注损伤、保护脑神经细胞、抗氧化、抗酒精中毒、调控骨代谢、降低眼压作用等。现就葛根素的药理作用作如下综述。%Objective:Puerarin is a single genus separated out of Radix Puerariae, isoflavones,it has a variety of pharmacological effects,pharmacological activity,definite efficacy. A lot of experimental research shows that, puerarin has anti-arrhythmic, against my-ocardial ischemia, the dilation of blood vessels, improve microcirculation, fall hematic fat, fall blood sugar, increase cerebral blood flow, anti cerebral ischemia-reperfusion injury, protect brain cells, antioxidant, alcohol poisoning, regulation bone metabolism, reduce intraocular pressure effect, etc. The pharmacological effects of puerarin is summarized as follow.

  3. Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

    Directory of Open Access Journals (Sweden)

    Trailović Saša M.

    2010-01-01

    Full Text Available Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD, act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

  4. Clinical Pharmacology of Ciprofloxacin in Neonates: Effects and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2017-06-01

    Full Text Available Ciprofloxacin is the most commonly used fluoroquinolone. Ciprofloxacin is prescribed for 1 in 44 Americans. Ciprofloxacin is a broad-spectrum bactericidal antibiotic, effective against both gram-positive and gram-negative bacteria, being especially active against the Enterobacteriacae, including many microorganisms resistant to penicillins, cephalosporins and aminoglycosides, and also is effective against Haemophilus influenzae, penicillinase-producing Neisseria gonorrhea, Campylobacter and Pseudomonas aeruginosa. Streptococci and pneumococci are weakly inhibited and there is a high incidence of staphylococcal resistance to ciprofloxacin. In neonates, the dose of ciprofloxacin is 10 mg/kg intravenously over 30-60 min infusion, and 20 mg/kg is used to treat Pseudomonas aeruginosa infection. Ciprofloxacin treatment is effective in life-threatening multi-drug resistant Pseudomonas aeruginosa. Ciprofloxacin may be administered by mouth and has a bioavailability of 70% and is mainly recovered unchanged in the urine. Ciprofloxacin is safe and well tolerated in infants. In neonates, the half-life of ciprofloxacin is 3-4 hours. For meningococcal prophylaxis, give a single dose of 30 mg/kg (up to a maximum of 125 mg orally. Ciprofloxacin is active against Citrobacter kosery that produces brain abscesses. The mortality rate for meningitis due to Citrobacter kosery is approximately 30%. Third-generation cephalosporins and aminoglycosides failed to prevent the high rates of morbidity and mortality caused by Citrobacter infections. Ciprofloxacin is the antibiotic treatment option for systemic infection or meningitis caused by Citrobacter kosery. Ciprofloxacin has been used to treat neonatal pneumonia, meningitis, and septicemia and was effective in all cases. The aim of this study is to review the clinical pharmacology of ciprofloxacin in neonates.

  5. Effects of pharmacological fiber supplements on levothyroxine absorption.

    Science.gov (United States)

    Chiu, A C; Sherman, S I

    1998-08-01

    To determine the effect of pharmacological fiber supplements, we measured levothyroxine (LT4) absorption without and with simultaneous ingestion of either calcium polycarbophil or psyllium hydrophilic mucilloid. Serum thyroxine (T4) levels in 8 volunteers were measured following ingestion of 600 microg of LT4 on 3 separate occasions at 4-week intervals: (1) LT4 alone; (2) LT4 together with 1000 mg polycarbophil; and (3) LT4 together with 3.4 g psyllium. The amount of absorbed LT4 was calculated as the incremental rise in serum T4 level during the first 6 hours multiplied by the volume of distribution for the hormone, and expressed as a percentage of the dose administered. Absorption of LT4 alone averaged 89% (95% confidence interval [CI]: 75%-104%), occurring at a median of 180 minutes. After simultaneous ingestion of calcium polycarbophil, LT4 absorption was 86% (95% CI: 74%-97%), occurring at 180 minutes. With simultaneous ingestion of psyllium and LT4, the absorption was 80% (95% CI: 64%-95%), occurring at 240 minutes. In summary, neither calcium polycarbophil nor psyllium hydrophilic mucilloid are likely to cause malabsorption of LT4 that could be detected by these methods.

  6. 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

  7. Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice.

    Directory of Open Access Journals (Sweden)

    Shakir D Alsharari

    Full Text Available Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c. for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile.

  8. Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice.

    Science.gov (United States)

    Alsharari, Shakir D; King, Justin R; Nordman, Jacob C; Muldoon, Pretal P; Jackson, Asti; Zhu, Andy Z X; Tyndale, Rachel F; Kabbani, Nadine; Damaj, M Imad

    2015-01-01

    Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c.) for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile.

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

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    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...

  10. Research progess on pharmacological action of Terminalia chebula Retz%诃子药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    李斌; 李鑫; 范源

    2015-01-01

    Terminalia chebula Retz. is the dried ripe fruit,which is come from Terminalia chebula Retz. or Terminalia chebula Retz. var. tomentella Kurt,its chemical activation component is mainly in tannins and phenolic acids. Modern phar-macological research had shown that myrobalan had antioxidant,hypoglycemic,hypolipidemic,disease resistance microbial, anti - inflammatory,analgesic,anti tumour,treatment of Alzheimer's disease and antitussive,pharmacological effects. In this article,we reviewed the new pharmacological research advances about Terminalia chebula Retz. ,in order to provide the ref-erence for the clinical science and rational drug use,and laid the foundation for its further research and development.%诃子系使君子科植物诃子或绒毛诃子的干燥成熟果实,其药效组分主要有鞣质酚酸类、三萜类及多糖类等。现代药理学研究表明诃子具有抗氧化、降血糖、调血脂、抗病原微生物、抗炎、镇痛、抗肿瘤、治疗阿尔茨海默病及镇咳等多种药理作用。本文拟对近年来诃子药理作用研究新进展进行综述,以期为其临床科学、合理用药提供一定参考,为其进一步研究与开发奠定基础。

  11. The Chemical Constituents and Pharmacological Effects of Bryophyllum calycinum. A review

    OpenAIRE

    Ali Esmail Al-Snafi

    2014-01-01

    Bryophyllum calycinum belongs to the family crassulaceae was widely used in traditional medicine especially in the tropical areas. The plant contained alkaloids, phenols, flavonoids, tannins, anthocyanins, glycosides, bufadienolides, saponins, coumarins, sitosterols, quinines, carotenoids, tocopherol and lectins . The previous pharmacological studies showed that it exerted many pharmacological effects including anticancer , antioxidant immunomodulating , antibacterial , anthelmentic , antipro...

  12. PHYTOCHEMICAL, PHARMACOLOGICAL AND PHARMACOKINETICS EFFECTS OF ROSMARINIC ACID

    Directory of Open Access Journals (Sweden)

    Rahul Bhatt

    2013-04-01

    Full Text Available Rosmarinic acid is natural polyphenol antioxidant isolated from Rosmarinus officinalis L. and commonly found in species of the Boraginaceae and the subfamily Nepetoideae of the Lamiaceae. RA species of Labiatae named Salvia officinalis, Rosmarinus officinali. RA exhibits important biological activities include its anti-carcinogenic, antiviral, antibacterial antimicrobial, antidepressant qualities. Plants of Labiatae family have been used in traditional medicine for exhaustion, phytotherapy, weakness, depression, and memory enhancement, circulation improvement, strengthening of fragile blood vessels, inflammation, and infection CNS disorder. RA showed the highest concentrations of antioxidant all the polyphenols. It is a red-orange powder that is slightly soluble in water, but well soluble in most organic solvents. RA polyphenolic compounds have been associated with antioxidative action in biological systems, acting as scavengers of singlet oxygen and free radicals. RA protects neurons from oxidative stress significantly attenuated H2O2-induced reactive oxygen species (ROS generation and apoptotic cell death and could contribute at least in part to neuroprotective effects because this natural compound exerts neuroprotective and anti-oxidative effects against neurotoxin insult in dopaminergic cells. This review focused on pharmacokinetics and use different uses of RA as antioxidant agent, anti-inflammatory, antiviral, photo protective, anticancer, antidepressant, and possible neuroprotective agent mechanism of actions.

  13. Cocaine: Pharmacology, Effects, and Treatment of Abuse. National Institute on Drug Abuse Research Monograph 50.

    Science.gov (United States)

    Grabowski, John, Ed.

    This monograph consists of eight papers which refer in one way or another to the pharmacology of cocaine. The papers are: (1) Cocaine 1984: Introduction and Overview" (John Grabowski); (2) "Cocaine: A Growing Public Health Problem" (Edgar H. Adams and Jack Durell); (3) "Neural Mechanisms of the Reinforcing Action of…

  14. Role of PPARγ in the nutritional and pharmacological actions of carotenoids

    Directory of Open Access Journals (Sweden)

    Zhao WE

    2016-04-01

    Full Text Available Wen-en Zhao,1 Guoqing Shi,2 Huihui Gu,1,3 Nguyen Ba Ngoc1,4 1School of Chemical Engineering and Energy, Zhengzhou University, 2School of Food and Bioengineering, Zhengzhou University of Light Industry, 3School of Life Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Faculty of Food Industry, College of Food Industry, Da Nang, Vietnam Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ has been shown to play an important role in the biological effects of carotenoids. The PPARγ-signaling pathway is involved in the anticancer effects of carotenoids. Activation of PPARγ partly contributes to the growth-inhibitory effects of carotenoids (β-carotene, astaxanthin, bixin, capsanthin, lutein, and lycopene on breast cancer MCF7 cells, leukemia K562 cells, prostate cancer (LNCaP, DU145, and PC3 cells, and esophageal squamous cancer EC109 cells. PPARγ is the master regulator of adipocyte differentiation and adipogenesis. Downregulated PPARγ and PPARγ-target genes have been associated with the suppressive effects of β-carotene and lycopene on 3T3L1 and C3H10T1/2 adipocyte differentiation and adipogenesis. ß-Carotene is cleaved centrally into retinaldehyde by BCO1, the encoding gene being a PPARγ-target gene. Retinaldehyde can be oxidized to retinoic acid and also be reduced to retinol. β-Carotene can also be cleaved asymmetrically into β-apocarotenals and β-apocarotenones by BCO2. The inhibitory effects of β-carotene on the development of adiposity and lipid storage are dependent substantially on BCO1-mediated production of retinoids. The effects of β-carotene on body adiposity were absent in BCO1-knockout mice. Retinoid metabolism is connected with the activity of PPARγ in the control of body-fat reserves. Retinoic acid, retinaldehyde, retinol, and β-apocarotenals exert suppressive effects on preadipocyte differentiation and adipogenesis via downregulation of PPARγ expression in cell culture. The

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

    Directory of Open Access Journals (Sweden)

    Huiying Li

    2014-01-01

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

  16. 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...

  17. II. Unbound versus total serum gold concentration: pharmacological actions on cellular function.

    Science.gov (United States)

    Lorber, A; Kunishima, D H; Harralson, A F; Simon, T M

    1983-08-01

    Unbound serum gold (UBSG) has received little attention, possibly because of rapid in vivo decay and in vivo concentration below the range of existing analytical procedures. We have recently developed a methodology enabling quantitation and study of UBSG during chrysotherapy to assess effects on cellular functions. UBSG after gold administration is labile, declining rapidly after attaining peak values at which lymphocyte mitogen response and polymorphonuclear phagocytosis were observed to be suppressed. Oral gold, i.e., auranofin, 3 mg BID as compared to systemic chrysotherapy 50 mg/wk, resulted in a higher percentage of UBSG to total serum gold.

  18. 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.

  19. Action orientation overcomes the ego depletion effect.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

  20. Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action

    Science.gov (United States)

    Ai, Xiao-yu; Liu, Hui-juan; Lu, Cheng; Liang, Cai-li; Sun, Yan; Chen, Shuang; Sun, Bo; Li, Yang; Liu, Yan-rong; Zhang, Qiang; Liu, Xue-qiang; Xiao, Ting; Jing, Xue-shuang; Sun, Tao; Zhou, Hong-gang; Yang, Cheng

    2017-01-01

    Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could accelerate dermal wound healing and strong inflammation control in Sprague-Dawley rats (SD rat) and Bama minipigs. Due to its low solubility, PnAg led to low toxicity and blood enrichment in animals. Furthermore, PnAg could upregulate the promoter activity of Jak, Stat3, and Stat3 downstream proteins. Therefore, PnAg may serve as an effective therapeutic compound for wound healing through regulating the gp130/Jak/Stat3 signaling pathway.

  1. 香豆素类化合物的药理作用研究进展%The Study Progress on Pharmacological Action of Coumarins

    Institute of Scientific and Technical Information of China (English)

    张国铎; 李航

    2011-01-01

    香豆素(coumarins)是一类广泛存在于自然界中的天然化合物,具有广泛的药理作用,如抗肿瘤、抗人类免疫缺陷病毒(HIV)、抗氧化、抗茵、抗凝血、光敏等.同时已有研究证实,其药理作用与化学结构密切相关,因此可进一步研究开发更多的香豆素类化合物,从中寻找有效的先导化舍物和活性基团,通过结构修饰和筛选,开发出高效低毒的临床药物.该文就近年来香豆素类化合物在肿瘤、艾滋病等治疗领域的研究作一综述.%Coumarins are a group of important natural compounds,and have been found to have multi-biological activities such as anti tumor, anti - HIV, antioxidant, anti - microbial, anticoagulation, photoresponse, etc.At the same time, some researches had confirmed that its pharmacological effect is closely related to its chemical structure.Therefore, more coumarin compounds could be developed by further researches, from which we could find effective leading compounds and active groups.High efficiency and low toxin clinical drugs can be developed by structure modification and selection.Progress on pharmacological action of coumarins were overviewed in this paper.

  2. Study on Pharmacological Action of Aqueous Extract from Melaleuca Ahemifolia%互叶白千层水提物药理作用研究*

    Institute of Scientific and Technical Information of China (English)

    李燕婧; 钟正贤; 林霄; 刘布鸣

    2013-01-01

      目的:观察互叶白千层水提物的药理作用。方法:采用巴豆油致小鼠耳廓肿胀法、微量2倍稀释法、小鼠热板法、小鼠被动皮肤过敏试验、豚鼠磷酸组胺致痒试验等试验方法观察互叶白千层水提物的药理作用,并对其进行急性毒性试验。结果:互叶白千层水提物能抑制巴豆油引起小鼠耳廓肿胀;提高小鼠热刺激疼痛的痛阈值;对金黄色葡萄球菌、表皮葡萄球菌、大肠埃希杆菌、白色念珠菌有较强抑菌作用;抑制小鼠被动皮肤通透性;增加豚鼠耐受磷酸组胺的致痒阈;互叶白千层水提物的最大给药量为225.62 g生药/kg。结论:互叶白千层水提物具有抗炎、镇痛、抗菌、抗过敏、止痒等药理作用,且毒性小。%Objective: To observe the pharmacological action of aqueous extract from Melaleuca Ahemifolia. Methods: The experiments concluded mice ear-swollen induced by croton oil, double broth dilution method, hot plate test, passive cutaneous anaphylaxis (PCA)in mouse, cavy itch test by histamine phosphate and acute toxicity test to observe the pharmacological action of aqueous extract from Melaleuca Ahemifolia. Results: Aqueous Extract from Melaleuca Ahemifolia can inhibit the mice ear-swollen induced by croton oil, enhance the threshold of pain in mice due to hot stimulation, provide obvious bacteriostatic ac-tion on staphylococcus aureus, staphylococcus epidermidis, bacillus coli and albicans Saccharomyces, reduce the PCA and im-prove cavy itch-threshold by histamine phosphate. The acute toxicity test showed that maximum tolerance of water extract of melaleuca alternifolia was 225.62 g crude drug/kg. Conclusion: Aqueous Extract from Melaleuca Ahemifolia can provide obvious anti-inflammatory, analgesic, antimicrobial, anti-allergic and antipruritic effects, with low toxicity.

  3. Wilsonian Effective Action of Superstring Theory

    CERN Document Server

    Sen, Ashoke

    2016-01-01

    By integrating out the heavy fields in type II or heterotic string field theory one can construct the effective action for the light fields. This effective theory inherits all the algebraic structures of the parent theory and the effective action automatically satisfies the Batalin-Vilkovisky quantum master equation. This theory is manifestly ultraviolet finite, has only light fields as its explicit degrees of freedom, and the Feynman diagrams of this theory reproduce the exact scattering amplitudes of light states in string theory to any arbitrary order in perturbation theory. Furthermore in this theory the degrees of freedom of light fields above certain energy scale are also implicitly integrated out. This energy scale is determined by a particular parameter labelling a family of equivalent actions, and can be made arbitrarily low, leading to the interpretation of the effective action as the Wilsonian effective action.

  4. Wilsonian effective action of superstring theory

    Science.gov (United States)

    Sen, Ashoke

    2017-01-01

    By integrating out the heavy fields in type II or heterotic string field theory one can construct the effective action for the light fields. This effective theory inherits all the algebraic structures of the parent theory and the effective action automatically satisfies the Batalin-Vilkovisky quantum master equation. This theory is manifestly ultraviolet finite, has only light fields as its explicit degrees of freedom, and the Feynman diagrams of this theory reproduce the exact scattering amplitudes of light states in string theory to any arbitrary order in perturbation theory. Furthermore in this theory the degrees of freedom of light fields above certain energy scale are also implicitly integrated out. This energy scale is determined by a particular parameter labelling a family of equivalent actions, and can be made arbitrarily low, leading to the interpretation of the effective action as the Wilsonian effective action.

  5. Rebound effect of drugs: fatal risk of conventional treatment and pharmacological basis of homeopathic treatment

    Directory of Open Access Journals (Sweden)

    Marcus Zulian Teixeira

    2012-06-01

    Full Text Available The homeopathic model applies the secondary action or vital reaction of the organism as a therapeutic method and thus prescribes treatment by similitude, which consists in administering to ill individuals substances that cause similar symptoms in healthy individuals. The vital, homeostatic or paradoxical reaction of the organism might be explained scientifically by means of the rebound effect of modern drugs, which might cause fatal iatrogenic events after discontinuation of antipathic (a term used in alternative medicine for palliative treatment, also known as enantiopathic treatment. Although the rebound effect is studied by modern pharmacology, it is poorly communicated to and discussed among healthcare professionals, who are thus deprived of information needed for the safe management of modern drugs. This article presents an up-to-date review on the rebound effect of modern drugs that grounds the homeopathic principle of healing and calls the attention of doctors to this type of adverse effect that is usually unnoticed. The rebound effect of modern palliative drugs, which was pointed out by Hahnemann more than two centuries ago, might cause fatal adverse events and is illustrated by the examples of acetylsalicylic acid, anti-inflammatory agents, bronchodilators, antidepressants, statins, proton-pump inhibitors, etc. Although the rebound effect is expressed by a small fraction of (susceptible individuals and might be avoided by gradual tapering of antipathic drugs, it exhibits epidemiologic importance as a function of the massive use of such palliative drugs and the lack of knowledge in its regard.

  6. Vacuum effective action: semiclassical approach

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, I L [Departamento de Fisica, ICE, Universidade Federal de Juiz de Fora, MG (Brazil)

    2007-11-15

    We present a brief review of quantum corrections to the action of gravity. The main attention is concentrated on the quantum theory of matter fields (QFT) on classical metric background. The list of most interesting possible applications of quantum corrections includes inflation and the Dark Energy problem. We show that both problems can be, in principle, resolved within the semiclassical theory, without invoking quantum gravity or string theory.

  7. Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model.

    Science.gov (United States)

    Serrano, Oscar K; Parrow, Nermi L; Violet, Pierre-Christian; Yang, Jacqueline; Zornjak, Jennifer; Basseville, Agnes; Levine, Mark

    2015-10-01

    Because 5-year survival rates for patients with metastatic melanoma remain below 25%, there is continued need for new therapeutic approaches. For some tumors, pharmacologic ascorbate treatment may have a beneficial antitumor effect and may work synergistically with standard chemotherapeutics. To investigate this possibility in melanoma, we examined the effect of pharmacologic ascorbate on B16-F10 cells. Murine models were employed to compare tumor size following treatment with ascorbate, and the chemotherapeutic agents dacarbazine or valproic acid, alone or in combination with ascorbate. Results indicated that nearly all melanoma cell lines were susceptible to ascorbate-mediated cytotoxicity. Compared to saline controls, pharmacologic ascorbate decreased tumor size in both C57BL/6 (P ascorbate was superior or equivalent to dacarbazine as an antitumor agent. Synergy was not apparent when ascorbate was combined with either dacarbazine or valproic acid; the latter combination may have additional toxicities. Pharmacologic ascorbate induced DNA damage in melanoma cells, as evidenced by increased phosphorylation of the histone variant, H2A.X. Differences were not evident in tumor samples from C57BL/6 mice treated with pharmacologic ascorbate compared to tumors from saline-treated controls. Together, these results suggest that pharmacologic ascorbate has a cytotoxic effect against melanoma that is largely independent of lymphocytic immune functions and that continued investigation of pharmacologic ascorbate in cancer treatment is warranted.

  8. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

    Science.gov (United States)

    Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2017-01-01

    The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. PMID:28850074

  9. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Alejandro M. S. Mayer

    2017-08-01

    Full Text Available The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

  10. The Advances in Research on the Pharmacological Effects of Fructus Ligustri Lucidi

    Directory of Open Access Journals (Sweden)

    Zunting Pang

    2015-01-01

    Full Text Available Fructus Ligustri Lucidi is a well-known invigorator in Chinese materia medica with hepatoprotective effect, anticancer activity, antioxidant activity, and so on. And oleanolic acids are the major pharmacologically active components in Fructus Ligustri Lucidi. So it has great value in medical health, and may be developed to a complementary and alternative medicine through further research. In this paper, the advances in research on pharmacological effects of Fructus Ligustri Lucidi were summarized by reviewing the recent related literature.

  11. The effect of taurine on chronic heart failure: actions of taurine against catecholamine and angiotensin II.

    Science.gov (United States)

    Ito, Takashi; Schaffer, Stephen; Azuma, Junichi

    2014-01-01

    Taurine, a ubiquitous endogenous sulfur-containing amino acid, possesses numerous pharmacological and physiological actions, including antioxidant activity, modulation of calcium homeostasis and antiapoptotic effects. There is mounting evidence supporting the utility of taurine as a pharmacological agent against heart disease, including chronic heart failure (CHF). In the past decade, angiotensin II blockade and β-adrenergic inhibition have served as the mainstay in the treatment of CHF. Both groups of pharmaceutical agents decrease mortality and improve the quality of life, a testament to the critical role of the sympathetic nervous system and the renin--angiotensin system in the development of CHF. Taurine has also attracted attention because it has beneficial actions in CHF, in part by its demonstrated inhibition of the harmful actions of the neurohumoral factors. In this review, we summarize the beneficial actions of taurine in CHF, focusing on its antagonism of the catecholamines and angiotensin II.

  12. The effect of learning styles and study behavior on success of preclinical students in pharmacology

    Science.gov (United States)

    Asci, Halil; Kulac, Esin; Sezik, Mekin; Cankara, F. Nihan; Cicek, Ekrem

    2016-01-01

    Objectives: To evaluate the effect of learning styles and study behaviors on preclinical medical students’ pharmacology exam scores in a non-Western setting. Materials and Methods: Grasha–Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success. Results: Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender. Conclusions: Preclinical medical students’ study behaviors are independent predictive factors for short-term pharmacology success. PMID:26997716

  13. The effect of learning styles and study behavior on success of preclinical students in pharmacology.

    Science.gov (United States)

    Asci, Halil; Kulac, Esin; Sezik, Mekin; Cankara, F Nihan; Cicek, Ekrem

    2016-01-01

    To evaluate the effect of learning styles and study behaviors on preclinical medical students' pharmacology exam scores in a non-Western setting. Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success. Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender. Preclinical medical students' study behaviors are independent predictive factors for short-term pharmacology success.

  14. Pharmacological mechanisms underlying the cardiovascular effects of the "bath salt" constituent 3,4-methylenedioxypyrovalerone (MDPV).

    Science.gov (United States)

    Schindler, Charles W; Thorndike, Eric B; Suzuki, Masaki; Rice, Kenner C; Baumann, Michael H

    2016-12-01

    3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here, we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. Male Sprague-Dawley rats had telemetry transmitters surgically implanted for the measurement of BP and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles. Following drug treatment, cardiovascular parameters were monitored for 3 h sessions. Racemic MDPV (0.3-3.0 mg·kg(-1) ) increased BP and HR in a dose-dependent manner. The S(+) enantiomer (0.3-3.0 mg·kg(-1) ) of MDPV produced similar effects, while the R(-) enantiomer (0.3-3.0 mg·kg(-1) ) had no effects. Neither of the hydroxylated phase I metabolites of MDPV altered cardiovascular parameters significantly from baseline. Pretreatment with the ganglionic blocker chlorisondamine (1 and 3 mg·kg(-1) ) antagonized the increases in BP and HR produced by 1 mg·kg(-1) MDPV. The α1 -adrenoceptor antagonist prazosin (0.3 mg·kg(-1) ) attenuated the increase in BP following MDPV, while the β-adrenoceptor antagonists propranolol (1 mg·kg(-1) ) and atenolol (1 and 3 mg·kg(-1) ) attenuated the HR increases. The S(+) enantiomer appeared to mediate the cardiovascular effects of MDPV, while the metabolites of MDPV did not alter BP or HR significantly; MDPV increased BP and HR through activation of central sympathetic outflow. Mixed-action α/β-adrenoceptor antagonists may be useful as treatments in counteracting the adverse cardiovascular effects of MDPV. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  15. [Study on main pharmacodynamic effects for Schisandra lignans based upon network pharmacology].

    Science.gov (United States)

    Qiu, Hong-tao; Zhao, Xiao-ping; Li, Zheng; Wang, Lin-li; Wang, Yi

    2015-02-01

    In this study, we focused on the study of pharmacodynamic effects for 6 major bioactive lignans of Schisandra chinensis, namely deoxyschizandrin, schisandrin B, schisandrin C, schisandrin, schizandrol B and schisantherin A. A compound-gene-pathway network, which contained 124 related genes and 88 pathways, was constructed by collecting drug genes through mining relevant literatures and network pharmacology analysis. Based on the network analysis, 32 pathways and 80 related genes were associated with inflammation, which implied that anti-inflammatory might be the major pharmacodynamic effects of these compounds. All lignans except schizandrol B reduced LPS-induced NO production in RAW264.7 cells, which validated the anti-inflammatory hypothesis generated from network analysis. Furthermore, we investigated the effects of deoxyschizandrin, schisandrin C, schisandrin and schisantherin A on the secretion of inflammatory cytokines TNF-α, IL-1β, IL-6, PGE2 and protein expressions of iNOS, COX-2. As a result, deoxyschizandrin showed the strongest anti-inflammatory activity with inhibitory effect on all 4 inflammatory cytokines secretions and protein expressions of iNOS, COX-2. This study provided evidences for systematic exploration on the pharmacolgical actions and mechanisms of schisandra.

  16. Discovery and pharmacological effects of a novel GPR142 antagonist.

    Science.gov (United States)

    Murakoshi, Michiko; Kuwabara, Harumi; Nagasaki, Miyuki; Xiong, Yu Mei; Reagan, Jeff D; Maeda, Hiroaki; Nara, Futoshi

    2017-06-01

    GPR142 is a G-protein-coupled receptor (GPCR), whose most potent and efficacious ligand has been reported as being the natural amino acid l-tryptophan. GPR142 is highly expressed in pancreatic β-cells and immune cells, suggesting the receptor may play a role in the pathogenesis and development of diabetes or inflammatory diseases. In a previous report, we developed GPR142 agonists as insulin secretagogues. In this report, we show the discovery of a selective, potent small-molecule GPR142 antagonist, CLP-3094, and its pharmacological characteristics. These data support targeting this receptor for the treatment of chronic inflammatory diseases.

  17. Recent advances in pharmacological effect of capsaicin%辣椒碱的药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    党元野; 陈修平; 张庆文; 王一涛

    2009-01-01

    Objective: To review the main pharmacological effects of capsaicin Methods: Literatures related to the pharmacological effects of capsaicin and the plausible mechanisms were collected, classified and summarized. Results: Capsaicin is a multiple functional natural product and exhibits many pharmacological effects, such as analgesic anti-inflammatory, cardiovascular protection, anticancer and digestive system protection. Conclusion: Capsaicin is a promising small chemical entity, which might be a potent drug in future though further studies needed to systematically evaluate its action and mechanisms.%目的:综述辣椒碱的主要药理作用.方法:查阅近年来国内外杂志中发表的关于辣椒碱的文献,对辣椒碱的主要药理作用及其可能的作用机制进行分析、总结.结果:辣椒碱具有消炎镇痛、心血管保护、抗癌以及消化系统保护等药理作用.结论:辣椒碱的药理作用比较广泛,是一个有发展潜力的小分子实体,在新药开发方面具有更加深入研究和探索的价值.

  18. Pharmacologic rationale underlying the therapeutic effects of tiotropium/olodaterol in COPD

    Directory of Open Access Journals (Sweden)

    Pelaia G

    2015-10-01

    Full Text Available Girolamo Pelaia,1 Alessandro Vatrella,2 Maria Teresa Busceti,1 Luca Gallelli,3 Cecilia Calabrese,4 Rosa Terracciano,3 Nicola Lombardo,1 Rosario Maselli11Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, 2Department of Medicine and Surgery, University of Salerno, Salerno, 3Department of Health Science, Magna Græcia University of Catanzaro, Catanzaro, 4Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Naples, ItalyAbstract: Bronchodilators are the most important drugs used for the treatment of chronic obstructive pulmonary disease (COPD. In particular, these therapeutic agents are mostly long-acting compounds utilized via inhalation, and include LAMA (long-acting muscarinic receptor antagonists and LABA (long-acting β2-adrenoceptor agonists. Because LAMA and LABA induce bronchodilation by distinct mechanisms of action, LABA/LAMA combinations provide a reciprocal potentiation of the pharmacological effects caused by each component. Hence, many COPD patients who do not achieve a satisfactory control of their symptoms using a single, either LAMA or LABA bronchodilator, can experience relevant benefits with the use of LAMA/LABA fixed combinations. Many different LAMA/LABA combinations have been recently developed and evaluated in randomized clinical trials. In this context, our review focuses on the pharmacological mechanisms underpinning the bronchodilation elicited by the LAMA tiotropium bromide and the LABA olodaterol. We also discuss the results of the most important clinical studies carried out in COPD patients to assess the efficacy and safety of tiotropium/olodaterol combinations.Keywords: LAMA, LABA, tiotropium, olodaterol, dual bronchodilation, tiotropium/olodaterol combinations

  19. A systems pharmacology perspective to decipher the mechanism of action of Parangichakkai chooranam, a Siddha formulation for the treatment of psoriasis.

    Science.gov (United States)

    Sundarrajan, Sudharsana; Arumugam, Mohanapriya

    2017-04-01

    Psoriasis is a chronic relapsing immune mediated disorder of the skin. The disease presents itself with well featured clinical and histological characteristics however the aetiology of the disease still remains obscure. The current systemic therapies aim to eliminate the symptoms of disease rather than offering a complete cure. Parangichakkai chooranam (PC), a Siddha oral herbal formulation has been widely prescribed for the treatment of psoriasis. Though the medication is highly prescribed by the Siddha healers the mechanism of PC for the treatment of psoriasis remains to be elucidated. The current study utilizes an integrated systems pharmacology approach to decipher the mechanism of action of PC. The comprehensive network pharmacological approach resulted in the construction of a Compound-Target network which encloses 155 compounds and 583 protein targets. A Disease-Target network was constructed by assembling disease proteins and their partners. When the compound targets were mapped to the network their involvement as controllers of the disease and triggers of disease associated comorbidities were identified. A Target-Pathway network raised from the pathway enrichment analysis not only identified disease specific pathways but also the pathways mediating secondary complications such as skin hemostasis, wound healing, desquamation and itch. The present work sheds light on the mechanism of action of PC in treating psoriasis. This work not only highlights the pharmacological action of the formulation but also emphasis on safe herbal remedies offered by the Siddha medicinal system. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Complex Effective Action and Schwinger Effect

    CERN Document Server

    Kim, Sang Pyo

    2016-01-01

    Spontaneous pair production from background fields or spacetimes is one of the most prominent phenomena predicted by quantum field theory. The Schwinger mechanism of production of charged pairs by a strong electric field and the Hawking radiation of all species of particles from a black hole are the consequence of nonperturbative quantum effects. In this review article, the vacuum structure and pair production is reviewed in the in-out formalism, which provides a consistent framework for quantum field theory in the sense that the complex action explains not only the vacuum persistence but also pair production. The current technology of intense lasers is still lower by a few order than the Schwinger limit for electron-positron pair production, while magnetic fields of magnetars on the surface are higher than the Schwinger limit and even higher at the core. On the other hand, the zero effective mass of electron and hole in graphene and Dirac or Weyl semimetals will open a window for experimental test of quantum...

  1. Healthspan Pharmacology.

    Science.gov (United States)

    Jafari, Mahtab

    2015-12-01

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

  2. Universality and ambiguity in fermionic effective actions

    CERN Document Server

    de Berredo-Peixoto, Guilherme; Shapiro, Ilya L

    2012-01-01

    We discuss an ambiguity in the one-loop effective action of massive fields which takes place in massive fermionic theories. The universality of logarithmic UV divergences in different space-time dimensions leads to the non-universality of the finite part of effective action, which can be called the non-local multiplicative anomaly. The general criteria of existence of this phenomena are formulated and applied to fermionic operators with different external fields.

  3. Comparative effectiveness and molecular pharmacological mechanisms of antiallergic agents on experimental conjunctivitis in mice.

    Science.gov (United States)

    Hu, S; Merayo-Lloves, J; Zhao, T; Foster, C S

    1998-02-01

    The purpose of this study was to determine the effectiveness of antiallergic agents in the treatment of experimental murine ragweed conjunctivitis. SWR/J mice were divided into eight groups: 1; normal controls (unmanipulated); 2, untreated; 3, lodoxamide; 4, cromolyn; 5, livocarbastine; 6, nedocromil; 7, buffer solution (BS); and 8, tetrandine (TDR). Groups 2-8 were exposed to ragweed pollen through topical application to conjunctival and nasal mucosa, followed by conjunctival challenge with the allergen. Allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) in conjunctiva was analyzed by reverse transcription polymerase chain reaction techniques. Exposed mice developed allergic conjunctivitis clinically and histologically that was modulated by topical lodoxamide, cromolyn, livocarbastine, or nedocromil eye drops or TDR intraperitoneally injected. Histopathologic analysis demonstrated that the drugs and TDR significantly reduced conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1beta and TNF-alpha mRNA gene expression in conjunctiva of treated mice was inhibited compared with untreated and BS-treated controls. No IL-6 mRNA expression was observed even on the conjunctiva of the untreated mice. The antiallergic drugs and TDR exerted a similar action on the murine model of allergic conjunctivitis and demonstrated pharmacologic effectiveness on the conjunctival mRNA expression of cytokines IL-1beta and TNF-alpha.

  4. Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors.

    Science.gov (United States)

    Antolín, Albert A; Mestres, Jordi

    2014-05-30

    PARP inhibitors hold promise as a novel class of targeted anticancer drugs. However, their true mechanism of action is still not well understood following recent reports that show marked differences in cellular effects. Here, we demonstrate that three PARP drug candidates, namely, rucaparib, veliparib, and olaparib, have a clearly different in vitro affinity profile across a panel of diverse kinases selected using a computational approach that relates proteins by ligand similarity. In this respect, rucaparib inhibits nine kinases with micromolar affinity, including PIM1, PIM2, PRKD2, DYRK1A, CDK1, CDK9, HIPK2, CK2, and ALK. In contrast, olaparib does not inhibit any of the sixteen kinases tested. In between, veliparib inhibits only two, namely, PIM1 and CDK9. The differential kinase pharmacology observed among PARP inhibitors provides a plausible explanation to their different cellular effects and offers unexplored opportunities for this drug class, but alerts also on the risk associated to transferring directly both preclinical and clinical outcomes from one PARP drug candidate to another.

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

    Science.gov (United States)

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

    2006-02-01

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

  6. Auto-modulation of neuroactive steroids on GABA A receptors: a novel pharmacological effect.

    Science.gov (United States)

    Wegner, Florian; Rassler, Cornelia; Allgaier, Clemens; Strecker, Karl; Wohlfarth, Kai

    2007-02-01

    GABA(A) receptor function is modulated by various important drugs including neuroactive steroids that act on allosteric modulatory sites and can directly activate GABA(A) receptor channels at high concentrations. We used whole cell patch-clamp recordings and rapid applications of the neuroactive steroid alphaxalone to investigate repetitive steroid effects. Alphaxalone potentiation of submaximal GABA-evoked currents was enhanced significantly by repetitive coapplications at all investigated recombinant isoforms (alpha1beta3delta, alpha1beta3gamma2L, alpha6beta3delta, alpha6beta3gamma2L) and at GABA(A) receptors of differentiated human NT2 neurons. A similar increase of current amplitudes was induced by repetitive applications of a high steroid concentration without GABA. We refer to these reversible effects as auto-modulation because repeated interactions of steroids enhanced their own pharmacological impact at the receptor sites in a time and concentration dependent manner without affecting GABA controls. Pronounced auto-modulatory actions were also measured using the neurosteroid 5alpha-THDOC in contrast to indiplon, THIP, and pentobarbital indicating a steroid specificity. Protein kinase A inhibition significantly reduced alphaxalone auto-modulation at alpha1beta3gamma2L, alpha6beta3gamma2L, and alpha6beta3delta subtypes while it enhanced potentiation at alpha1beta3delta isoforms suggesting a crucial influence of receptor subunit composition and phosphorylation for steroid actions. Especially at extrasynaptic GABA(A) receptor sites containing the delta subunit steroid auto-modulation may have a critical role in enhancing potentiation of GABA-induced currents.

  7. PhID: an open-access integrated pharmacology interactions database for drugs, targets, diseases, genes, side-effects and pathways.

    Science.gov (United States)

    Deng, Zhe; Tu, Weizhong; Deng, Zixin; Hu, Qian-Nan

    2017-09-14

    The current network pharmacology study encountered a bottleneck with a lot of public data scattered in different databases. There is the lack of open-access and consolidated platform that integrates this information for systemic research. To address this issue, we have developed PhID, an integrated pharmacology database which integrates >400,000 pharmacology elements (drug, target, disease, gene, side-effect, and pathway) and >200,000 element interactions in branches of public databases. The PhID has three major applications: (1) assists scientists searching through the overwhelming amount of pharmacology elements interaction data by names, public IDs, molecule structures, or molecular sub-structures; (2) helps visualizing pharmacology elements and their interactions with a web-based network graph; (3) provides prediction of drug-target interactions through two modules: PreDPI-ki and FIM, by which users can predict drug-target interactions of the PhID entities or some drug-target pairs they interest. To get a systems-level understanding of drug action and disease complexity, PhID as a network pharmacology tool was established from the perspective of data layer, visualization layer and prediction model layer to present information untapped by current databases. Database URL: http://phid.ditad.org/.

  8. Effective supergravity actions for conifold transitions

    Energy Technology Data Exchange (ETDEWEB)

    Mohaupt, Thomas; Saueressig, Frank E-mail: F.S.Saueressig@phys.uu.nl

    2005-03-01

    We construct gauged supergravity actions which describe the dynamics of M-theory on a Calabi-Yau threefold in the vicinity of a conifold transition. The actions explicitly include N charged hypermultiplets descending from wrapped M2-branes which become massless at the conifold point. While the vector multiplet sector can be treated exactly, we approximate the hypermultiplet sector by the non-compact Wolf spaces X(1+N). The effective action is then uniquely determined by the charges of the wrapped M2-branes. (author)

  9. Action-based effects on music perception

    Directory of Open Access Journals (Sweden)

    Pieter-Jan eMaes

    2014-01-01

    Full Text Available The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral phenomena. In contrast, embodied accounts to music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework capturing the ways that the human motor system, and the actions it produces, can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modelling, and vice versa, to predict the sensory outcomes of planned actions (forward modelling. Embodied accounts typically adhere to inverse modelling to explain action effects on music perception (Leman, 2007. We extent this account by pinpointing forward modelling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system, and the action it produces, suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music cognition in the sense that it needs to be considered as a dynamic process, in which aspects of action, perception, introspection, and social interaction are of crucial

  10. Action-based effects on music perception

    Science.gov (United States)

    Maes, Pieter-Jan; Leman, Marc; Palmer, Caroline; Wanderley, Marcelo M.

    2013-01-01

    The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance. PMID:24454299

  11. Action-effect bindings and ideomotor learning in intention- and stimulus-based actions

    Directory of Open Access Journals (Sweden)

    Arvid eHerwig

    2012-10-01

    Full Text Available According to ideomotor theory, action-effect associations are crucial for voluntary action control. Recently, a number of studies started to investigate the conditions that mediate the acquisition and application of action-effect associations by comparing actions carried out in response to exogenous stimuli (stimulus-based with actions selected endogenously (intention-based. There is evidence that the acquisition and/or application of action-effect associations is boosted when acting in an intention-based action mode. For instance, bidirectional action-effect associations were diagnosed in a forced choice test phase if participants previously experienced action-effect couplings in an intention-based but not in a stimulus-based action mode. The present study aims at investigating effects of the action mode on action-effect associations in more detail. In a series of experiments, we compared the strength and durability of short-term action-effect associations (binding immediately following intention- as well as stimulus-based actions. Moreover, long-term action-effect associations (learning were assessed in a subsequent test phase. Our results show short-term action-effect associations of equal strength and durability for both action modes. However, replicating previous results, long-term associations were observed only following intention-based actions. These findings indicate that the effect of the action mode on long-term associations cannot merely be a result of accumulated short-term action-effect bindings. Instead, only those episodic bindings are selectively perpetuated or retrieved that integrate action-relevant aspects of the processing event, i.e., in case of intention-based actions, the link between action and ensuing effect.

  12. PHARMACOLOGICAL EFFECTS OF SNAKE VENOM L- AMINO ACID OXIDASES

    Directory of Open Access Journals (Sweden)

    Joseph Baby

    2011-02-01

    Full Text Available L-Amino acid oxidases are flavoenzymes which catalyze the stereospecific oxidative deamination of an L-amino acid substrate to a corresponding a-ketoacid with hydrogen peroxide and ammonia production. These enzymes, which are widely distributed in many different organisms, exhibit a marked affinity for hydrophobic amino acids, including phenylalanine, tryptophan, tyrosine, and leucine. Snake venom LAAO induces platelet aggregation and cytotoxicity in various cancer cell lines. The enzyme has antibacterial activity inhibiting the growth of Gram-positive (Bacillus subtilis and Gram-negative (Escherichia coli bacteria. Specific substrates for the isolated protein are L-phenylalanine, L-tryptophan, L-methionine and L-leucine. The enzyme is stable at low temperatures (−20 ºC, −70 ºC and loses its activity by heating at 70 ºC. These enzymes are postulated to be toxins that may be involved in the allergic inflammatory response and specifically associated with mammalian endothelial cells damage. However, in the last decade these enzymes have become an interesting subject for pharmacological, structural and molecular characterizations. Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents.

  13. Analysis of influence factors on pharmacological action of Traditional Chinese Medicine%影响中药药理作用的因素分析

    Institute of Scientific and Technical Information of China (English)

    周二付

    2015-01-01

    对中药药理作用产生影响的因素有很多,如环境因素、机体因素以及药物因素.本文详细的对中药药理作用的影响因素进行探讨和分析,为我国现代医疗科学研究中药药理提供科学高效的价值意义,旨在为同行业者提供一个参考依据.%There are many factors that influence the pharmacological effects of Traditional Chinese Medicine, such as environmental factors and organic factors, drug factors. It investigated and analyzed the influential factors on Chinese medicine pharmacological effects with the value significance in order to provide scientific and efficient Chinese medicine for pharmacological research of modern medical science and provide a reference for the industry.

  14. Analytic results for the effective action

    CERN Document Server

    Blau, Steven K; Wipf, Andreas; 10.1142/S0217751X91002549

    2009-01-01

    Motivated by the seminal work of Schwinger, we obtain explicit closed form expressions for the one-loop effective action in a constant electromagnetic field. We discuss both massive and massless charged scalars and spinors in two, three, and four dimensions. Both strong field and weak field limits are calculable. The latter limit results in an asymptotic expansion whose first term reproduces the Euler-Heisenberg effective Lagrangian. We use the zeta function renormalization prescription, and indicate its relationship to Schwinger's renormalized effective action.

  15. Effect of Pharmacologically-Induced Hypovolemia on Aerobic Capacity

    Science.gov (United States)

    Everett, Meghan E.; Lee, S. M. C.; Platts, S. H.

    2009-01-01

    Decreased peak oxygen consumption (VO2pk) and an elevated exercise heart rate (HR) response are associated with a reduction in plasma volume (PV) after space flight and bed rest, a space flight analog. Reduced VO2pk and submaximal exercise tolerance would negatively impact an astronaut s ability to perform near maximal work that would be required in the event of an emergency. We previously have administered IV furosemide followed by a low salt diet to model PV loss and orthostatic intolerance observed after spaceflight. Purpose: To determine whether a pharmacologically-induced reduction in PV results in decreased VO2pk and elevated exercise HR response. Methods: Six subjects (5M, 1F) performed two graded peak cycle tests (work rate increased by 35 or 50 W every 3 min), once while normovolemic and once while hypovolemic. HR and expired respiratory gases were continuously measured. To induce hypovolemia, subjects were administered a single dose of IV furosemide (0.5 mg.kg-1) 30 hr before exercise testing and then consumed a low-salt diet (10 mEq.d(sup -1)). PV was measured using carbon monoxide rebreathing. Exercise HR and VO2 responses were quantified as the area under the curve (AUC) calculated over each quartile of the peak test, based on test time in the hypovolemia condition. Paired t-tests were used to test for differences in PV, VO2pk, and peak HR between conditions. Repeated-measures ANOVAs were used to test for differences in AUC between conditions. Results: PV (3.32+/-0.12 vs. 2.77+/-0.16 L, ppharmacologically-induced PV loss can be used to model microgravity-induced reductions in VO2pk.

  16. Effectiveness of student-led objective tutorials in pharmacology teaching to medical students.

    Science.gov (United States)

    Arora, Kriti; Hashilkar, Nayana Kamalnayan

    2016-10-01

    Current teaching in pharmacology is passive with less emphasis on clinical application. There is a need to incorporate newer instructional designs into pharmacology. Student-led objective tutorial (SLOT) is one of the novel designs to enhance interest among learners, provide opportunities for group learning, and facilitate self-directed learning. This study aims to assess the effectiveness of SLOTs over conventional tutorials (CTs) in pharmacology and to obtain feedback from the students regarding their perceptions about it. The regular batch of MBBS 2(nd) professional in pharmacology was randomly divided into two groups. Five topics from central nervous system (CNS) were selected. One group received SLOT as the instructional strategy, whereas the other group went through CTs. At the end of the module, a written test was conducted to assess the effectiveness of both strategies. The students provided feedback regarding their experience using a prevalidated questionnaire. The mean scores of both the groups were analyzed using Mann-Whitney U-test. There was no significant difference in the mean scores of the end of the module test. However, the overall passing percentage was significantly higher in the intervention group (P = 0.043). A total of 45.71% students favored it as a future tutorial method and expressed that SLOT enhanced their ability to learn independently. SLOT is an effective teaching-learning method to teach pharmacology to medical undergraduates. It enhances interest among learners and increases the ability to learn independently.

  17. A Novel Family of Small Molecules that Enhance the Intracellular Delivery and Pharmacological Effectiveness of Antisense and Splice Switching Oligonucleotides.

    Science.gov (United States)

    Wang, Ling; Ariyarathna, Yamuna; Ming, Xin; Yang, Bing; James, Lindsey I; Kreda, Silvia M; Porter, Melissa; Janzen, William; Juliano, Rudolph L

    2017-08-18

    The pharmacological effectiveness of oligonucleotides has been hampered by their tendency to remain entrapped in endosomes, thus limiting their access to cytosolic or nuclear targets. We have previously reported a group of small molecules that enhance the effects of oligonucleotides by causing their release from endosomes. Here, we describe a second novel family of oligonucleotide enhancing compounds (OECs) that is chemically distinct from the compounds reported previously. We demonstrate that these molecules substantially augment the actions of splice switching oligonucleotides (SSOs) and antisense oligonucleotides (ASOs) in cell culture. We also find enhancement of SSO effects in a murine model. These new compounds act by increasing endosome permeability and causing partial release of entrapped oligonucleotides. While they also affect the permeability of lysosomes, they are clearly different from typical lysosomotropic agents. Current members of this compound family display a relatively narrow window between effective dose and toxic dose. Thus, further improvements are necessary before these agents can become suitable for therapeutic use.

  18. Physiological and pharmacological effects of estrogens in breast cancer.

    Science.gov (United States)

    Leclercq, G; Heuson, J C

    1979-12-19

    Focus here is on the mechanism of action of both estrogens and antiestrogens at the tumor cell levels in breast cancer. The interactions of estrogens and their antagonists are emphasized and analyzed in terms of current and potential clinical applications to breast cancer treatment. This review deals with these interrelationships at the molecular levels, not just with general aspects of endocrine interrelationships. The article is divided into 8 main parts: 1) an introduction, which reviews historical understanding of receptor technology and significances; 2) main properties of estrogens and estrogen receptors; 3) the influence of estrogens and antiestrogens on growth of experimental mammary tumor systems; 4) the suppression of or administration of estrogens for treatment of advanced human breast cancer; 5) estrogen receptivity of mammary tumors; 6) progress in treatment of advanced breast cancer derived from studies on the mode of action of estrogens; 7) the prognostic significance of estrogens and estrogenic receptivity (the estriol theory); and 8) concluding remarks on the future paths of receptor research.

  19. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    Science.gov (United States)

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  20. Effects of hormone treatment on sexual functioning in postmenopausal women : pharmacological intervention and female sexuality

    NARCIS (Netherlands)

    Nijland, Esmé Aurelia

    2008-01-01

    Effects of hormone treatment on sexual functioning in postmenopausal women. Pharmacological intervention and female sexuality: a complex, controversial clinical and social issue. The studies presented in this thesis have been conducted to investigate the effects of hormone therapy (HT) and tibolone

  1. Effects of hormone treatment on sexual functioning in postmenopausal women : pharmacological intervention and female sexuality

    NARCIS (Netherlands)

    Nijland, Esmé Aurelia

    2008-01-01

    Effects of hormone treatment on sexual functioning in postmenopausal women. Pharmacological intervention and female sexuality: a complex, controversial clinical and social issue. The studies presented in this thesis have been conducted to investigate the effects of hormone therapy (HT) and tibolone

  2. Research Progress of Chemical Compositions and Pharmacological Actions of Mentha canadensis%薄荷化学成分与药理作用研究新进展

    Institute of Scientific and Technical Information of China (English)

    沈梅芳; 李小萌; 单琪媛

    2012-01-01

    Through searching literatures about Mentha canadensis at home and abroad in recent years,it is to summarize the chemical compositions,pharmacological actions and modern application in clinic, providing theory foundation for further developing of Mentha canadensis.%通过对薄荷在近几年国内外化学研究、药理作用方面相关文献的查阅,以及现代临床应用等方面的研究情况进行了总结,为进一步合理开发利用薄荷提供理论依据.

  3. Effective action for strongly correlated electron systems

    Energy Technology Data Exchange (ETDEWEB)

    Ferraz, A., E-mail: aferraz.iccmp@gmail.com [International Institute of Physics - UFRN, Department of Experimental and Theoretical Physics - UFRN, Natal (Brazil); Kochetov, E.A. [International Institute of Physics - UFRN, Natal (Brazil); Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation)

    2011-12-21

    The su(2|1) coherent-state path-integral representation of the partition function of the t-J model of strongly correlated electrons is derived at finite doping. The emergent effective action is compared to the one proposed earlier on phenomenological grounds by Shankar to describe holes in an antiferromagnet [R. Shankar, Nucl. Phys. B 330 (1990) 433]. The t-J model effective action is found to have an important 'extra' factor with no analogue in Shankar's action. It represents the local constraint of no double electron occupancy and reflects the rearrangement of the underlying phase-space manifold due to the presence of strong electron correlation. This important ingredient is shown to be essential to describe the physics of strongly correlated electron systems.

  4. Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature

    Directory of Open Access Journals (Sweden)

    Crippa José AS

    2012-01-01

    Full Text Available Abstract Background Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. Objective To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. Methods A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. Results The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. Conclusion Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil.

  5. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

    Full Text Available The sodium-glucose cotransporter (SGLT 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.

  6. 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.

  7. Variational Calculation of the Effective Action

    CERN Document Server

    Sugihara, T

    1998-01-01

    An indication of spontaneous symmetry breaking is found in the two-dimensional $\\lambda\\phi^4$ model, where an attention is payed to a functional form of an effective action. An effective energy, which is an effective action for a static field, is obtained as a functional of the classical field from the ground state of hamiltonian $H[J]$ interacting with a constant external field. The energy and wavefunction of the ground state are calculated in terms of DLCQ (Discretized Light-Cone Quantization) under antiperiodic boundary condition. A field configuration which is physically meaningful is found as a solution of the quantum mechanical Euler-Lagrange equation in the $J\\to 0$ limit. It is shown that there exists a nontrivial field configuration in the broken phase of $Z_2$ symmetry because of a boundary effect.

  8. Illustrating Caffeine's Pharmacological and Expectancy Effects Utilizing a Balanced Placebo Design.

    Science.gov (United States)

    Lotshaw, Sandra C.; And Others

    1996-01-01

    Hypothesizes that pharmacological and expectancy effects may be two principles that govern caffeine consumption in the same way they affect other drug use. Tests this theory through a balanced placebo design on 100 male undergraduate students. Expectancy set and caffeine content appeared equally powerful, and worked additionally, to affect…

  9. Systematic Review of the Effectiveness of Pharmacological Treatments for Adolescents and Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Broadstock, Marita; Doughty, Carolyn; Eggleston, Matt

    2007-01-01

    The variable expression of autism over the lifespan is likely to lead to different symptoms and support requirements, and to distinct responses to pharmacotherapy treatment, in older patients compared to children. This systematic review considers the effectiveness of pharmacological treatment in managing autism spectrum disorder in adolescents and…

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

    Science.gov (United States)

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

    2014-12-01

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

  11. 中药成分蓝雪醌的药理作用研究进展%Research Progress on Pharmacologic Actions of Plumbagin

    Institute of Scientific and Technical Information of China (English)

    冯筱巍

    2015-01-01

    Currently more and more scholars have focused on the research of natural compounds,as research and development of new drugs costs large investment,long period,and high risk.Plumbagin is one of the natural α-naphthoquinones compounds,it mainly exists in plumbago zeylanica and radix ceratostigmatis mini.It has been reported that the pharmacologic actions of plumbagin is widespread,including anti-oxidant, anti-inflammatory,antibacterial and anticancer.Here is to make a review of the pharmacologic actions and mechanism of plumbagin in order to provide new ideas for further development .%由于新药研发耗资大、周期长、风险高,越来越多的学者把目光投向天然产物的研究. 中药成分蓝雪醌是一种天然的α-萘醌类化合物,主要存在于紫金标、白花丹等药用植物中. 蓝雪醌的药理作用十分广泛,具有抗氧化、消炎止痛、抗肿瘤、抗菌等作用. 该文主要对蓝雪醌的药理作用及其作用机制进行总结归纳,为蓝雪醌的进一步开发利用提供思路.

  12. 绿茶多酚提取纯化工艺及药理作用%Extraction and purification technologies of green tea polyphenols and its pharmacological actions

    Institute of Scientific and Technical Information of China (English)

    张思佳; 黄璐; 牟峰

    2013-01-01

    绿茶多酚是绿茶的主要有效成分,多年研究发现绿茶多酚具有抗氧化、抗癌、抗肥胖、抗紫外线、抗龋齿等药理作用,且对神经退行性疾病和心血管系统疾病有一定的防治作用.本文对绿茶多酚近年来的提取纯化工艺及药理作用进行阐述,为绿茶的进一步开发提供参考.%Green tea polyphenols,which are major chemical constituents from green tea,have great pharmacological actions,such as antioxidant,anticancer,anti-obesity,anti-UV,against dental caries,improving cardiovascular function and neurodegenerative diseases.This review focused on the advances on extraction,purification technologies and pharmacological actions of green tea polyphenols in recent years.

  13. Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia

    Directory of Open Access Journals (Sweden)

    Vos Theo

    2011-05-01

    Full Text Available Abstract Background Information on cost-effectiveness of interventions to treat schizophrenia can assist health policy decision making, particularly given the lack of health resources in developing countries like Thailand. This study aims to determine the optimal treatment package, including drug and non-drug interventions, for schizophrenia in Thailand. Methods A Markov model was used to evaluate the cost-effectiveness of typical antipsychotics, generic risperidone, olanzapine, clozapine and family interventions. Health outcomes were measured in disability adjusted life years. We evaluated intervention benefit by estimating a change in disease severity, taking into account potential side effects. Intervention costs included outpatient treatment costs, hospitalization costs as well as time and travel costs of patients and families. Uncertainty was evaluated using Monte Carlo simulation. A sensitivity analysis of the expected range cost of generic risperidone was undertaken. Results Generic risperidone is more cost-effective than typicals if it can be produced for less than 10 baht per 2 mg tablet. Risperidone was the cheapest treatment with higher drug costs offset by lower hospital costs in comparison to typicals. The most cost-effective combination of treatments was a combination of risperidone (dominant intervention. Adding family intervention has an incremental cost-effectiveness ratio of 1,900 baht/DALY with a 100% probability of a result less than a threshold for very cost-effective interventions of one times GDP or 110,000 baht per DALY. Treating the most severe one third of patients with clozapine instead of risperidone had an incremental cost-effectiveness ratio of 320,000 baht/DALY with just over 50% probability of a result below three times GDP per capita. Conclusions There are good economic arguments to recommend generic risperidone as first line treatment in combination with family intervention. As the uncertainty interval indicates

  14. Effectiveness and cost-effectiveness of the pharmacological treatment of Alzheimer's disease and vascular dementia.

    Science.gov (United States)

    Versijpt, Jan

    2014-01-01

    Until an effective and especially disease-modifying treatment for Alzheimer's disease (AD) and vascular dementia (VaD) is available, the currently available pharmacological therapeutic arsenal aims at merely improving symptomatology. Health economic data make an important contribution to the planning of healthcare services and the estimation of the cost of drug reimbursement. As such, both for cholinesterase inhibitors and, to a lesser extent, for memantine it can be claimed that the direct cost of the drug itself is eclipsed by the cost savings associated with delaying institutionalization or delaying the time of progression into a more severe disease state. The present manuscript reviews several factors contributing to the costs of dementia, gives an overview of available studies claiming both the effectiveness and cost-effectiveness of current dementia treatments, and highlights strengths and weaknesses of the aforementioned studies.

  15. New insights into the pharmacological and toxicological effects of thalidomide.

    Science.gov (United States)

    Meierhofer, Christian; Wiedermann, Christian J

    2003-01-01

    The molecular activity of thalidomide comprises a wide range of mechanisms. Alteration of cytokine synthesis and release may be as important as changes in lymphocyte trafficking and leukocyte migration. Since endothelial cells play an important role in leukocyte extravasation and maintenance of inflammatory processes in the affected tissue, thalidomide-induced alterations of cellular adhesion molecules, and consequently changes of interaction of leukocytes with the endothelial cell layer, will result in modulation of the response in inflammation and immunity. Thalidomide mainly reduces tumor necrosis factor (TNF)-alpha production by macrophages, and its TNF alpha antagonist properties explain the beneficial effects in several TNF alpha-associated complications of severe diseases. Pathophysiologically relevant alterations most likely include gene regulatory effects, with interference in growth factor-dependent pathways known to be involved in teratogenesis, and effects on the transcriptional control of the inflammatory response via nuclear factor (NF)-kappa B. The effects of thalidomide, its enantiomers and analogs, on a broad range of diseases, and their differential pharmacokinetic and pharmacodynamic properties, give the scope for ongoing investigations in the search for analogs with better selectivity but without thalidomide-related side effects and teratogenicity.

  16. Review of the Pharmacological and Toxicological Effects of Salvia leriifolia

    Directory of Open Access Journals (Sweden)

    Hossein Hosseinzadeh

    2009-03-01

    Full Text Available Salvia leriifolia Benth. (vernacular names such as Nuruozak and Jobleh is a perennial herbaceous plant that grows exclusively in south and tropical regions of Khorasan and Semnan provinces, I. R. Iran. Unlike other species of Salvia genus, the chemical constituents of S. leriifolia are not well recognized. The stem oil of the plant consisted mainly both monoterpenes and sesquiterpenes, while in leaf and flower oils monoterpenes predominated over sesquiterpenes. In recent years, the different properties of this plant such as the attenuation of morphine dependence, hypoglycemic, antinociceptive and antiinflammatory, antioxidant, anti-ischemia, anticonvulsant, antiulcer effects, antibacterial activities and antimutagenic effects were evaluated. These effects introduce this plant for more toxicological and clinical trials evaluations as a herbal medicine.

  17. Effects of a pain program on nurses' pharmacological pain management.

    NARCIS (Netherlands)

    Francke, A.L.; Dingemans, W.A.; Borg, P.A.J.; Luiken, J.B.; Grypdonck, M.; Huijer-Abu Saad, H.

    1999-01-01

    Surgical nurses from five Dutch general hospitals participated in a continuing education program on pain assessment and management. Effects of the program were measured in a pretest-post-test control group design, in which nursing wards were randomly allocated to the experimental condition (program

  18. A review of the pharmacological effects of Arctium lappa (burdock).

    Science.gov (United States)

    Chan, Yuk-Shing; Cheng, Long-Ni; Wu, Jian-Hong; Chan, Enoch; Kwan, Yiu-Wa; Lee, Simon Ming-Yuen; Leung, George Pak-Heng; Yu, Peter Hoi-Fu; Chan, Shun-Wan

    2011-10-01

    Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock.

  19. Cognitive versus pharmacological effects of alcohol on assertiveness

    OpenAIRE

    2015-01-01

    M.A. (Clinical Psychology) The present study investigated the effect of expectancy and alcohol consumption on the assertive behaviour of female social drinkers, utilising a balanced-placebo design (Marlatt, Demming & Reid, 1973). Using the College Self Expression Scale (CSES) (Galassi et al, 1974) as the self report measure of assertiveness, and the Behavioral Assertiveness Test-Revised (Eisler et al. 1975) as the behavioural measure of assertiveness, analyses of variance were computed on ...

  20. Effects of a pain program on nurses' pharmacological pain management.

    OpenAIRE

    Francke, A.L.; Dingemans, W.A.; Borg, P.A.J.; Luiken, J.B.; Grypdonck, M; Huijer-Abu Saad, H.

    1999-01-01

    Surgical nurses from five Dutch general hospitals participated in a continuing education program on pain assessment and management. Effects of the program were measured in a pretest-post-test control group design, in which nursing wards were randomly allocated to the experimental condition (program,) or to the control condition (no program) It was found that the program led to an improvement of the quality of analgesic administration, and to an increase in the quantity of nonopioids administe...

  1. Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

    Directory of Open Access Journals (Sweden)

    Frederickson Martyn

    2010-01-01

    Full Text Available Abstract Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal

  2. CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

    NARCIS (Netherlands)

    VANDENBROEK, L; WIERDA, JMKH; SMEULERS, NJ; VANSANTEN, GJ; LECLERCQ, MGL; HENNIS, PJ

    1994-01-01

    Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating

  3. Effects of pharmacological ascorbate on hemoglobin-induced cancer cell proliferation.

    Science.gov (United States)

    Lu, Naihao; Ding, Yun; Tian, Rong; Yang, Zhen; Chen, Jianfa; Peng, Yi-Yuan

    2016-11-01

    The high heme content in red meat is associated with an increased risk of developing cancer. Pharmacologic concentrations of ascorbate can specifically kill a wide range of cancer cells. In this study, the impact of ascorbate at pharmacologic concentrations on hemoglobin (Hb)-modulated human hepatoma HepG2 cell survival was investigated. It was found that HepG2 cells were proliferated by Hb (5-25μM), but killed by high pharmacologic concentrations of ascorbate (2-10mM). Although ascorbate at the low pharmacologic concentration (0.5mM) alone exhibited insignificant effect on cell viability, it effectively inhibited Hb (10μM)-induced cancer cell proliferation. The mechanism of this cytotoxicity was based on the production of extracellular H2O2 and involved transition iron. The influence of ascorbate on Hb-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate) was further investigated to illustrate the reaction mechanism of ascorbate toxicity, where H2O2 was generated in the reaction of ascorbate with Hb. Furthermore, circular dichroism demonstrated no significant change in the secondary structure of Hb after ascorbate addition and molecular docking revealed binding modes of ascorbate with Hb. These results demonstrated that ascorbate could possess anti-cancer activity through interfering in Hb-dependent redox reactions.

  4. Chemical compounds and pharmacological effects of Rabdosia excisa

    Institute of Scientific and Technical Information of China (English)

    PANG Jinsong; YU Qian; LIU Bao

    2007-01-01

    Many kinds of diterpenoids have been isolated from Rabdosia spp.Some of them have anti-microbial effects,counteract inflammation,and inhibit tumor progression activities.We conducted the present study in order to look for bioactive compounds in the medicinal plant Rabdosia excisa.In this study,five compounds were isolated from R.excisa;they were oridonin,isokamebakaurin,oleanolie acid,ursolic acid,and β-sitosterol.In order to identify the function of the extracts,the activity of antibiotics,antioxidation,and immunity test were carried out against these functions.Prospective results were observed in all of the tested items.

  5. Pharmacological Effects of Antihypertensive Drugs in Elderly Patients

    Directory of Open Access Journals (Sweden)

    Alsu I. Abdrahmanova

    2016-11-01

    Full Text Available Introduction. The incidence of arterial hypertension (AH increases. Only 23% of Russian patients monitor their blood pressure. This affects the incidence of complications, the quality and duration of life. The largest number of deaths related to the irrational pharmacotherapy of hypertension occurs in the older age group. Methods. We have carried out a review of publications in scientific and medical literature, the analysis of the current state of views on the incidence, pathogenesis, and peculiarities of the treatment of hypertension in elderly patients. Results. An isolated systolic arterial hypertension (ISAH, typical of the elderly people, is associated with a reduction in the elasticity of the arterial walls. The reaction of the elderly to the medicines is largely determined by the severity of age-related changes. We have considered four factors influencing the effect of drugs such as absorption, distribution, metabolism and excretion of drugs. Discussion. Treatment in elderly patients is aimed at reducing the symptoms and compensating the disturbed functions. It is necessary to be able to detect that symptoms in the structure that affect quality of life and require therapeutic intervention. Physiological aging processes lead to changes in the pharmacokinetics and pharmacodynamics of drugs. The therapeutic effect is affected by changes in absorption, distribution volume, metabolism and excretion of drugs. In this connection there is an increased amount of drug in the bloodstream. Final Report. Knowing the geriatric aspects of cardiology is an important element of knowledge of a modern doctor.

  6. Geometrical effective action and Wilsonian flows

    CERN Document Server

    Pawlowski, J M

    2003-01-01

    A gauge invariant flow equation is derived by applying a Wilsonian momentum cut-off to gauge invariant field variables. The construction makes use of the geometrical effective action for gauge theories in the Vilkovisky-DeWitt framework. The approach leads to modified Nielsen identities that pose non-trivial constraints on consistent truncations. We also evaluate the relation of the present approach to gauge fixed formulations as well as discussing possible applications.

  7. Effect of Fuzheng Huayu formula and its actions against liver fibrosis.

    Science.gov (United States)

    Liu, Chenghai; Hu, Yiyang; Xu, Lieming; Liu, Cheng; Liu, Ping

    2009-06-29

    Liver fibrosis is a common histological process to develop into cirrhosis in various chronic liver diseases including chronic hepatitis and fatty liver. Therefore anti-liver fibrosis is very important strategy to treat chronic liver diseases. Fuzheng Huayu (FZHY), a preparation containing herbs such as Radix Salvia Miltiorrhizae, Cordyceps, Semen Persicae, was formulated on the basis of Chinese medicine theory in treating liver fibrosis and was approved. Pharmacological studies and clinical trials demonstrate that FZHY has a significant effect against liver fibrosis and that many of the pharmacological actions are attributable to the effect. This article reviews the effects and actions of FZHY, in particular the effects observed from clinical trials in treating liver fibrosis caused by chronic hepatitis B and the actions on inhibition of hepatic stellate cell activation, protection of hepatocytes and inhibition of hepatic sinusoidal capillarization. This article also reviews the coordinated effects of the constituent herbs of FZHY and the actions of their active compounds such as salvianonic acid B (SA-B) on liver fibrosis.

  8. Effect of Fuzheng Huayu formula and its actions against liver fibrosis

    Directory of Open Access Journals (Sweden)

    Xu Lieming

    2009-06-01

    Full Text Available Abstract Liver fibrosis is a common histological process to develop into cirrhosis in various chronic liver diseases including chronic hepatitis and fatty liver. Therefore anti-liver fibrosis is very important strategy to treat chronic liver diseases. Fuzheng Huayu (FZHY, a preparation containing herbs such as Radix Salvia Miltiorrhizae, Cordyceps, Semen Persicae, was formulated on the basis of Chinese medicine theory in treating liver fibrosis and was approved. Pharmacological studies and clinical trials demonstrate that FZHY has a significant effect against liver fibrosis and that many of the pharmacological actions are attributable to the effect. This article reviews the effects and actions of FZHY, in particular the effects observed from clinical trials in treating liver fibrosis caused by chronic hepatitis B and the actions on inhibition of hepatic stellate cell activation, protection of hepatocytes and inhibition of hepatic sinusoidal capillarization. This article also reviews the coordinated effects of the constituent herbs of FZHY and the actions of their active compounds such as salvianonic acid B (SA-B on liver fibrosis.

  9. Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review.

    Science.gov (United States)

    Wang, Zhi-Yong; Liu, Jian-Gang; Li, Hao; Yang, Hui-Ming

    2016-01-01

    Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.

  10. Review on pharmacological and toxicologyical effects of oleum azadirachti oil

    Directory of Open Access Journals (Sweden)

    Khaled MM Koriem

    2013-10-01

    Full Text Available Oleum azadirachti consists of the oil obtained from dried seeds of Azadirachta indica A. Juss. (family: Meliaceae. Local names of Azadirachta indica A. Juss. are Abodua, aforo-oyinbo, anwe egyane, arista, azad dirakht, azadarakht, azedarach and bead tree. Indigenous to India, and widely distributed in South and South-East Asia and cultivated in Africa, the South Pacific Islands, South and Central America and Australia, and in southern Florida and California, United States of America, it is a straight-boled deciduous tree, which is 6-25 m high. Bark is dark-brown, externally fissured with a buff inner surface and fibrous fracture. Leaves alternately arranged, pinnately compound and up to 40 cm long, and composed of 8-18 short-petiolate narrow-ovate, pointed and curved toothed leaflets, 3-10 cm long and 1-4 cm wide arranged in alternate pairs. The major constituents are oxidized tetranortriterpenes including azadirachtin (azadirachtin A, azadiriadione, epoxyazadiradione, azadirone, nimbidin, nimbin, deacetylnimbin, salannin, gedunin, mahmoodin, 17-hydroxydiradione and related derivatives. It is of various medicinal uses, such as a contraceptive for intravaginal use, a mosquito repellent, and treatment of vaginal infections, treatment of gastric ulcers, cardiovascular disease, malaria, rheumatism and skin disorders, external applications for treatment of septic wounds, ulcers and boils, treatment of allergic skin reactions, asthma, bruises, colic, conjunctivitis, dysmenorrhoea, fever, gout, headache, itching due to varicella, kidney stones, leukorrhoea, psoriasis, scabies, sprains and muscular pain, and wounds. It is also used as an emmenagogue, tonic, stomatic and vermicide. In conclusion, the plant oil had antifertility, antihyperglycaemic, anti-inflammatory, antimicrobial, antiviral, antiulcer, estrogenic, immune, contraceptive, antibacterial, insect repellent, and skin treatment effects.

  11. Review on pharmacological and toxicologyical effects of oleum azadirachti oil

    Institute of Scientific and Technical Information of China (English)

    Khaled MM Koriem

    2013-01-01

    Oleum azadirachti consists of the oil obtained from dried seeds of Azadirachta indica A. Juss. (family: Meliaceae). Local names of Azadirachta indica A. Juss. are Abodua, aforo-oyinbo, anwe egyane, arista, azad dirakht, azadarakht, azedarach and bead tree. Indigenous to India, and widely distributed in South and South-East Asia and cultivated in Africa, the South Pacific Islands, South and Central America and Australia, and in southern Florida and California, United States of America, it is a straight-boled deciduous tree, which is 6-25 m high. Bark is dark-brown, externally fissured with a buff inner surface and fibrous fracture. Leaves alternately arranged, pinnately compound and up to 40 cm long, and composed of 8-18 short-petiolate narrow-ovate, pointed and curved toothed leaflets, 3-10 cm long and 1-4 cm wide arranged in alternate pairs. The major constituents are oxidized tetranortriterpenes including azadirachtin (azadirachtin A), azadiriadione, epoxyazadiradione, azadirone, nimbidin, nimbin, deacetylnimbin, salannin, gedunin, mahmoodin, 17-hydroxydiradione and related derivatives. It is of various medicinal uses, such as a contraceptive for intravaginal use, a mosquito repellent, and treatment of vaginal infections, treatment of gastric ulcers, cardiovascular disease, malaria, rheumatism and skin disorders, external applications for treatment of septic wounds,ulcers and boils, treatment of allergic skin reactions, asthma, bruises, colic, conjunctivitis, dysmenorrhoea, fever, gout, headache, itching due to varicella, kidney stones, leukorrhoea, psoriasis, scabies, sprains and muscular pain, and wounds. It is also used as an emmenagogue, tonic, stomatic and vermicide. In conclusion, the plant oil had antifertility, antihyperglycaemic, anti-inflammatory, antimicrobial, antiviral, antiulcer, estrogenic, immune, contraceptive, antibacterial, insect repellent, and skin treatment effects.

  12. Review on pharmacological and toxicologyical effects of oleum azadirachti oil.

    Science.gov (United States)

    Koriem, Khaled M M

    2013-10-01

    Oleum azadirachti consists of the oil obtained from dried seeds of Azadirachta indica A. Juss. (family: Meliaceae). Local names of Azadirachta indica A. Juss. are Abodua, aforo-oyinbo, anwe egyane, arista, azad dirakht, azadarakht, azedarach and bead tree. Indigenous to India, and widely distributed in South and South-East Asia and cultivated in Africa, the South Pacific Islands, South and Central America and Australia, and in southern Florida and California, United States of America, it is a straight-boled deciduous tree, which is 6-25 m high. Bark is dark-brown, externally fissured with a buff inner surface and fibrous fracture. Leaves alternately arranged, pinnately compound and up to 40 cm long, and composed of 8-18 short-petiolate narrow-ovate, pointed and curved toothed leaflets, 3-10 cm long and 1-4 cm wide arranged in alternate pairs. The major constituents are oxidized tetranortriterpenes including azadirachtin (azadirachtin A), azadiriadione, epoxyazadiradione, azadirone, nimbidin, nimbin, deacetylnimbin, salannin, gedunin, mahmoodin, 17-hydroxydiradione and related derivatives. It is of various medicinal uses, such as a contraceptive for intravaginal use, a mosquito repellent, and treatment of vaginal infections, treatment of gastric ulcers, cardiovascular disease, malaria, rheumatism and skin disorders, external applications for treatment of septic wounds, ulcers and boils, treatment of allergic skin reactions, asthma, bruises, colic, conjunctivitis, dysmenorrhoea, fever, gout, headache, itching due to varicella, kidney stones, leukorrhoea, psoriasis, scabies, sprains and muscular pain, and wounds. It is also used as an emmenagogue, tonic, stomatic and vermicide. In conclusion, the plant oil had antifertility, antihyperglycaemic, anti-inflammatory, antimicrobial, antiviral, antiulcer, estrogenic, immune, contraceptive, antibacterial, insect repellent, and skin treatment effects.

  13. Expectancy and Pharmacology Influence the Subjective Effects of Nicotine using a Balanced-Placebo Design

    OpenAIRE

    Kelemen, William L.; Kaighobadi, Farnaz

    2007-01-01

    The expectancy and pharmacological effects of nicotine (0.60 mg) on memory and the subjective effects of cigarettes were examined using a balanced-placebo design (i.e., expect either nicotine or no nicotine and receive either nicotine or no nicotine). A total of 120 college students who smoke were assigned to 1 of the 4 experimental groups and rated the cigarettes on a number of dimensions and completed questionnaires on smoking urges, tension, and energy. Participants also completed tests of...

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

    Science.gov (United States)

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

    2010-10-01

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

  15. Holographic Heavy-Light Chiral Effective Action

    CERN Document Server

    Liu, Yizhuang

    2016-01-01

    We propose a variant of the $D4$-$D8$ construction to describe the low energy effective theory of heavy-light mesons, interacting with the lowest lying pseudoscalar and vector mesons. The heavy degrees of freedom are identified with the $D8_L$-$D8_H$ string low energy modes, and are approximated near the world volume of $N_f-1$ light $D8_L$ branes, by fundamental vector field valued in $U(N_f-1)$. The effective action follows from the reduction of the bulk D-brane Born-Infeld (DBI) and Chern-Simons (CS) actions, and is shown to exhibit both chiral and heavy-quark symmetry. The action interpolates continuously between the $U(N_f)$ case with massless mesons, and the $U(N_f-1)$ case with heavy-light mesons. The heavy-light meson radial spectrum is Regge-like. The one-pion and two-pion couplings to the heavy-light multiplets are evaluated. The partial widths for the charged decays $G\\rightarrow H+\\pi$ are shown to be comparable to the recently reported full widths for both the charm and bottom mesons.

  16. Effective actions for relativistic fluids from holography

    CERN Document Server

    de Boer, Jan; Pinzani-Fokeeva, Natalia

    2015-01-01

    Motivated by recent progress in developing action formulations of relativistic hydrodynamics, we use holography to derive the low energy dissipationless effective action for strongly coupled conformal fluids. Our analysis is based on the study of novel double Dirichlet problems for the gravitational field, in which the boundary conditions are set on two codimension one timelike hypersurfaces (branes). We provide a geometric interpretation of the Goldstone bosons appearing in such constructions in terms of a family of spatial geodesics extending between the ultraviolet and the infrared brane. Furthermore, we discuss supplementing double Dirichlet problems with information about the near-horizon geometry. We show that upon coupling to a membrane paradigm boundary condition, our approach reproduces correctly the complex dispersion relation for both sound and shear waves. We also demonstrate that upon a Wick rotation, our formulation reproduces the equilibrium partition function formalism, provided the near-horiz...

  17. Mining Molecular Pharmacological Effects from Biomedical Text: a Case Study for Eliciting Anti-Obesity/Diabetes Effects of Chemical Compounds.

    Science.gov (United States)

    Dura, Elzbieta; Muresan, Sorel; Engkvist, Ola; Blomberg, Niklas; Chen, Hongming

    2014-05-01

    In the pharmaceutical industry, efficiently mining pharmacological data from the rapidly increasing scientific literature is very crucial for many aspects of the drug discovery process such as target validation, tool compound selection etc. A quick and reliable way is needed to collect literature assertions of selected compounds' biological and pharmacological effects in order to assist the hypothesis generation and decision-making of drug developers. INFUSIS, the text mining system presented here, extracts data on chemical compounds from PubMed abstracts. It involves an extensive use of customized natural language processing besides a co-occurrence analysis. As a proof-of-concept study, INFUSIS was used to search in abstract texts for several obesity/diabetes related pharmacological effects of the compounds included in a compound dictionary. The system extracts assertions regarding the pharmacological effects of each given compound and scores them by the relevance. For each selected pharmacological effect, the highest scoring assertions in 100 abstracts were manually evaluated, i.e. 800 abstracts in total. The overall accuracy for the inferred assertions was over 90 percent.

  18. Clinical Analysis the Pharmacologic Action of Alprostadil%前列地尔的药理作用临床分析

    Institute of Scientific and Technical Information of China (English)

    赵娟

    2016-01-01

    Alprostadil the common drugs in treatment of chronic disease, there has speciifc function of elderly patient clinical therapy, which is continuously extending the clinial appplication range, has higher value of clinical application. At present, the clinical application study increase gradually about the pharmacologic action of alprostadil. This article analysis the research progress, pharmacologic, application status of alprostadil, aim at provide some reference in alprostadil clinical application.%前列地尔是治疗较多慢性疾病的常用药,其在老年疾病的临床治疗中有特殊的作用,临床应用范围也不断扩大,有较高的临床应用价值。当前,关于前列地尔药理作用及临床应用研究逐渐增多,本文对前列地尔应用现状、药理作用及研究进展进行分析,以期为前列地尔临床应用提供借鉴。

  19. Assessment of the effectiveness of non-pharmacological methods in pain relief during labor

    Directory of Open Access Journals (Sweden)

    Samara Maria Borges Osório

    2014-04-01

    Full Text Available This is a systematic review that aimed to evaluate the effectiveness of non-pharmacological methods for pain relief during labor. The articles’ selection was based on BDENF, PubMed, LILACS and Cochrane Library, published between 2007 and 2012. One analyzed seven studies that assessed the non-pharmacological methods and met the eligibility criteria. It was evident that massage, aromatherapy, immersion bath, acupuncture and acupressure are effective methods to relieve pain during labor, because besides reducing pain perception, they still lower levels of anxiety and stress. Among them, the most efficient one was the massage, mainly when done in the first stage of labor. Furthermore, the interventions don’t interfere in the kind and duration of labor, being safe to clinical practice.

  20. The pharmacological effects of Salvia species on the central nervous system.

    Science.gov (United States)

    Imanshahidi, Mohsen; Hosseinzadeh, Hossein

    2006-06-01

    Salvia is an important genus consisting of about 900 species in the family Lamiaceae. Some species of Salvia have been cultivated world wide for use in folk medicine and for culinary purposes. The dried root of Salvia miltiorrhiza, for example, has been used extensively for the treatment of coronary and cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis, S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with important pharmacological effects. In this review, the pharmacological effects of Salvia species on the central nervous system will be reviewed. These include sedative and hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic, memory enhancing, anticonvulsant, neuroprotective and antiparkinsonian activity, as well as the inhibition of ethanol and morphine withdrawal syndrome.

  1. Effects of Pharmacologic and Genetic Inhibition of Alk on Cognitive Impairments in NF1 Mutant Mice

    Science.gov (United States)

    2016-08-01

    behavioral and cognitive testing than originally anticipated. In addition, as a minimal number of mice was provided to us for breeding of the NF1 and Alk...AWARD NUMBER: W81XWH-13-1-0117 TITLE: Effects of Pharmacologic and Genetic Inhibition of Alk on Cognitive Impairments in NF1 Mutant Mice...including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and

  2. Progress of Chemical Composition and Pharmacological Effects of Meretrix meretrix Linnaeus

    Institute of Scientific and Technical Information of China (English)

    Du; Zhengcai; Hou; Xiaotao; Huang; Qing; Deng; Jiagang; Fanshi; Fangcao

    2014-01-01

    Meretrix meretrix Linnaeus is a traditional marine drug. There are more than two thousand years of history using clamshell as a component of medicine.After a review of relevant literature at home and abroad for nearly 20 years,the author summarized chemical composition and pharmacological effects of M. meretrix,in order to provide a scientific basis for further development and utilization of M. meretrix.

  3. Constraining the D3-brane effective action

    CERN Document Server

    Basu, Anirban

    2008-01-01

    We consider higher derivative corrections of the type D^{2k} R^2 in the effective action of the D3-brane with trivial normal bundle. Based on the perturbative disc and annulus amplitudes, and constraints of supersymmetry and duality, we argue that these interactions are protected, at least for small values of k. Their coefficient functions receive only a finite number of perturbative contributions, and non-perturbative contributions from D-instantons. We propose expressions for these modular forms for low values of k.

  4. The influence of action effects in task switching

    Directory of Open Access Journals (Sweden)

    Sarah eLukas

    2013-01-01

    Full Text Available According to ideomotor theories, intended effects caused by a certain action are anticipated before action execution. In the present study, we examined the question of whether action effects play a role in cued task switching. In our study, the participants practiced task-response-effect mappings in an acquisition phase, in which action effects occur after a response in a certain task context. In the ensuing transfer phase, the previously practiced mappings were changed in a random, unpredictable task-response-effect mapping. When changed into unpredictable action effects, RT as well as switch costs increased, but this occurred mainly in trials with short preparation time and not with long preparation time. Moreover, switch costs were generally smaller with predictable action effects than with unpredictable action effects. This suggests that anticipated task-specific action effects help to activate the relevant task set before task execution when the task is not yet already prepared based on the cue.

  5. Effective action theory of Andreev level spectroscopy

    Science.gov (United States)

    Galaktionov, Artem V.; Zaikin, Andrei D.

    2015-12-01

    With the aid of the Keldysh effective action technique we develop a microscopic theory describing Andreev level spectroscopy experiments in nontunnel superconducting contacts. We derive an effective impedance of such contacts which accounts for the presence of Andreev levels in the system. At subgap bias voltages and low temperatures, inelastic Cooper pair tunneling is accompanied by transitions between these levels resulting in a set of sharp current peaks. We evaluate the intensities of such peaks, establish their dependence on the external magnetic flux piercing the structure and estimate the thermal broadening of these peaks. We also specifically address the effect of capacitance renormalization in a nontunnel superconducting contact and its impact on both the positions and heights of the current peaks. At overgap bias voltages, the I -V curve is determined by quasiparticle tunneling and contains current steps related to the presence of discrete Andreev states in our system.

  6. 双苄基异喹啉类生物碱的心血管药理作用%Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives

    Institute of Scientific and Technical Information of China (English)

    钱家庆

    2002-01-01

    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.

  7. Review of pharmacological effects of Myrtus communis L. and its active constituents.

    Science.gov (United States)

    Alipour, Ghazal; Dashti, Saeedeh; Hosseinzadeh, Hossein

    2014-08-01

    Myrtle (Myrtus communis L., Myrtaceae) is a medicinal herb used worldwide in traditional medicine. A large number of components have been isolated from this herb. Polyphenols, myrtucommulone (MC), semimyrtucommulone (S-MC), 1,8-cineole, α-pinene, myrtenyl acetate, limonene, linalool and α-terpinolene are among the compounds considered to be the main biologically active components. Various parts of this herb such as its berries, leaves and fruits have been used extensively as a folk medicine for several centuries. The herb is used traditionally for the treatment of disorders such as diarrhea, peptic ulcer, hemorrhoid, inflammation, pulmonary and skin diseases, although clinical and experimental studies suggest that it possesses a broader spectrum of pharmacological and therapeutic effects such as antioxidative, anticancer, anti-diabetic, antiviral, antibacterial, antifungal, hepatoprotective and neuroprotective activity. The present review attempts to give an overview on the phytochemical, pharmacological, toxicological and clinical studies of total extracts and the most relevant active ingredients of M. communis.

  8. CNS pharmacological effects of the hydroalcoholic extract of Sida cordifolia L. leaves.

    Science.gov (United States)

    Franco, C I F; Morais, L C S L; Quintans-Júnior, L J; Almeida, R N; Antoniolli, A R

    2005-04-26

    Sida cordifolia L. (Malvaceae), known as "malva branca", is a plant used in the popular medicine for the treatment stomatits, of asthma and nasal congestion. This work researched the acute toxicity of Sida cordifolia and its action on the central nervous system (CNS) because no data in the literature have been found about of pharmacological activity of this plant in the CNS. The hydroalcoholic extract of Sida cordifolia leaves (HESc) was used and the psychopharmacology approach began with the determination of LD(50), where a low toxicity was observed in mice. Depressive activity on CNS was demonstrated by several alterations in mice's behavior in the pharmacological screening. In the motility test, the HESc showed significant reduction of spontaneous activity at a dose of 1000 mg/kg (i.p.) at 30 and 60 min. The same form the HESc also decreased the ambulation and rearing in open-field test at 30, 60 and 120 min at a dose of 1000 mg/kg (i.p.).

  9. Effective action for stochastic partial differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Hochberg, David [Laboratorio de Astrofisica Espacial y Fisica Fundamental, Apartado 50727, 28080 Madrid, (Spain); Centro de Astrobiologia, INTA, Carratera Ajalvir, Km. 4, 28850 Torrejon, Madrid, (Spain); Molina-Paris, Carmen [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Perez-Mercader, Juan [Laboratorio de Astrofisica Espacial y Fisica Fundamental, Apartado 50727, 28080 Madrid, (Spain); Visser, Matt [Physics Department, Washington University, Saint Louis, Missouri 63130-4899 (United States)

    1999-12-01

    Stochastic partial differential equations (SPDEs) are the basic tool for modeling systems where noise is important. SPDEs are used for models of turbulence, pattern formation, and the structural development of the universe itself. It is reasonably well known that certain SPDEs can be manipulated to be equivalent to (nonquantum) field theories that nevertheless exhibit deep and important relationships with quantum field theory. In this paper we systematically extend these ideas: We set up a functional integral formalism and demonstrate how to extract all the one-loop physics for an arbitrary SPDE subject to arbitrary Gaussian noise. It is extremely important to realize that Gaussian noise does not imply that the field variables undergo Gaussian fluctuations, and that these nonquantum field theories are fully interacting. The limitation to one loop is not as serious as might be supposed: Experience with quantum field theories (QFTs) has taught us that one-loop physics is often quite adequate to give a good description of the salient issues. The limitation to one loop does, however, offer marked technical advantages: Because at one loop almost any field theory can be rendered finite using zeta function technology, we can sidestep the complications inherent in the Martin-Siggia-Rose formalism (the SPDE analog of the Becchi-Rouet-Stora-Tyutin formalism used in QFT) and instead focus attention on a minimalist approach that uses only the physical fields (this ''direct approach'' is the SPDE analog of canonical quantization using physical fields). After setting up the general formalism for the characteristic functional (partition function), we show how to define the effective action to all loops, and then focus on the one-loop effective action and its specialization to constant fields: the effective potential. The physical interpretation of the effective action and effective potential for SPDEs is addressed and we show that key features carry over from

  10. Effective action for stochastic partial differential equations.

    Science.gov (United States)

    Hochberg, D; Molina-París, C; Pérez-Mercader, J; Visser, M

    1999-12-01

    Stochastic partial differential equations (SPDEs) are the basic tool for modeling systems where noise is important. SPDEs are used for models of turbulence, pattern formation, and the structural development of the universe itself. It is reasonably well known that certain SPDEs can be manipulated to be equivalent to (nonquantum) field theories that nevertheless exhibit deep and important relationships with quantum field theory. In this paper we systematically extend these ideas: We set up a functional integral formalism and demonstrate how to extract all the one-loop physics for an arbitrary SPDE subject to arbitrary Gaussian noise. It is extremely important to realize that Gaussian noise does not imply that the field variables undergo Gaussian fluctuations, and that these nonquantum field theories are fully interacting. The limitation to one loop is not as serious as might be supposed: Experience with quantum field theories (QFTs) has taught us that one-loop physics is often quite adequate to give a good description of the salient issues. The limitation to one loop does, however, offer marked technical advantages: Because at one loop almost any field theory can be rendered finite using zeta function technology, we can sidestep the complications inherent in the Martin-Siggia-Rose formalism (the SPDE analog of the Becchi-Rouet-Stora-Tyutin formalism used in QFT) and instead focus attention on a minimalist approach that uses only the physical fields (this "direct approach" is the SPDE analog of canonical quantization using physical fields). After setting up the general formalism for the characteristic functional (partition function), we show how to define the effective action to all loops, and then focus on the one-loop effective action and its specialization to constant fields: the effective potential. The physical interpretation of the effective action and effective potential for SPDEs is addressed and we show that key features carry over from QFT to the case of

  11. Total RNA-seq to identify pharmacological effects on specific stages of mRNA synthesis.

    Science.gov (United States)

    Boswell, Sarah A; Snavely, Andrew; Landry, Heather M; Churchman, L Stirling; Gray, Jesse M; Springer, Michael

    2017-03-06

    Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation. Compared to well-characterized elongation inhibitors that target CDK9, isoginkgetin caused RNA polymerase accumulation within a broader promoter-proximal band, indicating that elongation inhibition by isoginkgetin occurs after release from promoter-proximal pause. RNA-seq distinguished isoginkgetin and CDK9 inhibitors from topoisomerase I inhibition, which alters elongation across gene bodies. We were able to detect these and other specific defects in mRNA synthesis at low sequencing depth using simple metagene-based metrics. These metrics now enable total-RNA-seq-based screening for high-throughput identification of pharmacological effects on individual stages of mRNA synthesis.

  12. [Effectiveness of non-pharmacological interventions in the quality of life of caregivers of Alzheimer].

    Science.gov (United States)

    Amador-Marín, Bárbara; Guerra-Martín, María Dolores

    Explore the effectiveness of non-pharmacological interventions to improve the quality of life of family caregivers of Alzheimer's patients. We conducted a systematic review, in pairs, in the following databases: PubMed, Scopus, CINAHL, PsycINFO, WOS, Cochrane Library, IME, Cuiden Plus and Dialnet. Inclusion criteria were: 1. Studies published between 2010-2015. 2. Language: English, Portuguese and Spanish. 3. Randomized controlled clinical trials. 4. Score greater than or equal to 3 on the Jadad scale. 13 studies were included. Four performed a psychosocial intervention with family caregivers, three psychotherapeutic, two psychoeducational, two multicomponent, one educational and another with mutual support groups. The tools to assess quality of life: three studies used the Health Status Questionnaire (HSQ), three EuroQol-5D (two only used the EVA), two health questionnaire SF-36, two WHOQOL-BREF, two Quality of Life SF-12 and one Perceived Quality of Life Scale (PQoL). Regarding the effectiveness of non-pharmacological interventions, five studies obtained favorable results in the quality of life after psychotherapeutic interventions and community-type multicomponent training. The diversity of non-pharmacological interventions used and contents, differences in the number of sessions and hours, and variability of valuation tools used to measure quality of life of family caregivers, leads us to reflect on the appropriateness to standardize criteria, for the sake to improve clinical practice. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Exploring soft constraints on effective actions

    CERN Document Server

    Bianchi, Massimo; Huang, Yu-tin; Lee, Chao-Jung; Wen, Congkao

    2016-01-01

    We study effective actions for simultaneous breaking of space-time and internal symmetries. Novel features arise due to the mixing of Goldstone modes under the broken symmetries which, in contrast to the usual Adler's zero, leads to non-vanishing soft limits. Such scenarios are common for spontaneously broken SCFT's. We explicitly test these soft theorems for $\\mathcal{N}=4$ sYM in the Coulomb branch both perturbatively and non-perturbatively. We explore the soft constraints systematically utilizing recursion relations. In the pure dilaton sector of a general CFT, we show that all amplitudes up to order $s^{n} \\sim \\partial^{2n}$ are completely determined in terms of the $k$-point amplitudes at order $s^k$ with $k \\leq n$. Terms with at most one derivative acting on each dilaton insertion are completely fixed and coincide with those appearing in the conformal DBI, i.e. DBI in AdS. With maximal supersymmetry, the effective actions are further constrained, leading to new non-renormalization theorems. In particu...

  14. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease

    Science.gov (United States)

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

    2015-01-01

    The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo. Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF. PMID:26469778

  15. Effectiveness of Revised Pharmacology Record Books as a Teaching-Learning Method for Second Year Medical Students

    Science.gov (United States)

    Gangadhar, Reneega

    2016-01-01

    Introduction The goal of teaching medical undergraduates Pharmacology is to form a sound foundation of therapeutics. The pharmacology record books are maintained as a part of the curriculum. The purpose of this study was to obtain feedback of the medical students about the new record adopted in the institution after major revision Materials and Methods This was a questionnaire based study done in a Government Medical College of Kerala in February 2013. The data was analysed using SPSS. The feedback on clinical pharmacology exercises was given positive and negative scores. Results Majority (64.5%) opined that the content in pharmacology record was good. A total of 78.1% completed the record during discussions in practical classes. Majority wrote the records for understanding pharmacology. For 79.8% General Pharmacology exercises were most relevant, 33.8% considered Clinical Pharmacology exercises to be the most thought provoking. Drug use in special groups received the maximum positive score. Conclusion The new improved pharmacology record is an effective teaching-learning method. Inclusion of more clinically oriented exercises has increased the interest of the students in the subject. PMID:26894083

  16. The Universal One-Loop Effective Action

    CERN Document Server

    Drozd, Aleksandra; Quevillon, Jérémie; You, Tevong

    2016-01-01

    We present the universal one-loop effective action for all operators of dimension up to six obtained by integrating out massive, non-degenerate multiplets. Our general expression may be applied to loops of heavy fermions or bosons, and has been checked against partial results available in the literature. The broad applicability of this approach simplifies one-loop matching from an ultraviolet model to a lower-energy effective field theory (EFT), a procedure which is now reduced to the evaluation of a combination of matrices in our universal expression, without any loop integrals to evaluate. We illustrate the relationship of our results to the Standard Model (SM) EFT, using as an example the supersymmetric stop and sbottom squark Lagrangian and extracting from our universal expression the Wilson coefficients of dimension-six operators composed of SM fields.

  17. Pharmacological effects of methamphetamine and alpha-PVP vapor and injection.

    Science.gov (United States)

    Marusich, Julie A; Lefever, Timothy W; Blough, Bruce E; Thomas, Brian F; Wiley, Jenny L

    2016-07-01

    Vaporizing drugs in e-cigarettes is becoming a common method of administration for synthetic cathinones and classical stimulants. Heating during vaporization can expose the user to a cocktail of parent compound and thermolytic degradants, which could lead to different toxicological and pharmacological effects compared to ingesting the parent compound alone via injection or nasal inhalation. This study examined the in vivo toxicological and pharmacological effects of vaporized and injected methamphetamine (METH) and α-pyrrolidinopentiophenone (α-PVP). Male and female ICR mice were administered METH or α-PVP through vapor or i.p. injection. Dose-effect curves were determined for locomotor activity and a functional observational battery (FOB). METH and α-PVP vapor were also evaluated for place preference in male mice. Vapor exposure and injection led to more similarities than differences in toxicological and pharmacological effects. In the FOB, both routes of administration produced typical stimulant effects, and injection also increased some bizarre behaviors (e.g. licking, teeth chattering, darting). Both METH and α-PVP vapor exposure produced conditioned place preference. The two routes of administration had comparable efficacy in locomotor activation, with vapor producing longer lasting effects than injection. Females showed greater METH-induced locomotor activity, and greater incidence of a few somatic signs in the FOB than males. These results explore the toxicology of stimulant vapor inhalation in mice using an e-cigarette device. Despite the current technological and methodological difficulties, studying drug vapor promises to allow determination of toxicological effects of thermolytic products and flavor additives.

  18. Effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depression: a systematic review (METACHRON

    Directory of Open Access Journals (Sweden)

    von Wolff Alessa

    2010-11-01

    Full Text Available Abstract Background Chronic depressions represent a substantial part of depressive disorders and are associated with severe consequences. Several studies were performed addressing the effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depressions. Yet, a systematic review comparing the effectiveness of multiple treatment options and considering all subtypes of chronic depressions is still missing. Methods/Design Aim of this project is to summarize empirical evidence on efficacy and effectiveness of treatments for chronic depression by means of a systematic review. The primary objectives of the study are to examine, which interventions are effective; to examine, if any differences in effectiveness between active treatment options exist; and to find possible treatment effect modifiers. Psychotherapeutic, pharmacological, and combined treatments will be considered as experimental interventions and no treatment, wait-list, psychological/pharmacological placebo, treatment as usual, and other active treatments will be seen as comparators. The population of patients will include adults with chronic major depression, dysthymia, double depression, or recurrent depression without complete remission between episodes. Outcomes of the analyses are depressive symptoms, associated consequences, adverse events, and study discontinuation. Only randomized controlled trials will be considered. Discussion Given the high prevalence and serious consequences of chronic depression and a considerable amount of existing primary studies addressing the effectiveness of different treatments the present systematic review may be of high relevance. Special attention will be given to the use of current methodological standards. Findings are likely to provide crucial information that may help clinicians to choose the appropriate treatment for chronically depressed patients.

  19. Large scale integration of drug-target information reveals poly-pharmacological drug action mechanisms in tumor cell line growth inhibition assays

    Science.gov (United States)

    Knight, Richard A.; Gostev, Mikhail; Ilisavskii, Sergei; Willis, Anne E.; Melino, Gerry; Antonov, Alexey V.

    2014-01-01

    Understanding therapeutic mechanisms of drug anticancer cytotoxicity represents a key challenge in preclinical testing. Here we have performed a meta-analysis of publicly available tumor cell line growth inhibition assays (~ 70 assays from 6 independent experimental groups covering ~ 500 000 molecules) with the primary goal of understanding molecular therapeutic mechanisms of cancer cytotoxicity. To implement this we have collected currently available information on protein targets for molecules that were tested in the assays. We used a statistical methodology to identify protein targets overrepresented among molecules exhibiting cancer cytotoxicity with the particular focus of identifying overrepresented patterns consisting of several proteins (i.e. proteins “A” and “B” and “C”). Our analysis demonstrates that targeting individual proteins can result in a significant increase (up to 50-fold) of the observed odds for a molecule to be an efficient inhibitor of tumour cell line growth. However, further insight into potential molecular mechanisms reveals a multi-target mode of action: targeting a pattern of several proteins drastically increases the observed odds (up to 500-fold) for a molecule to be tumour cytotoxic. In contrast, molecules targeting only one protein but not targeting an additional set of proteins tend to be nontoxic. Our findings support a poly-pharmacology drug discovery paradigm, demonstrating that anticancer cytotoxicity is a product, in most cases, of multi-target mode of drug action PMID:24553133

  20. Effects of Reinforcement Method of Dissection Physiology Education on the Achievement in Pharmacology.

    Science.gov (United States)

    Kitayama, Tomoya; Kagota, Satomi; Yoshikawa, Noriko; Kawai, Nobuyuki; Nishimura, Kanae; Miura, Takeshi; Yasui, Naomi; Shinozuka, Kazumasa; Nakabayashi, Toshikatsu

    2016-01-01

     The Pharmaceutical Education Support Center was established in the Department of Pharmacy at the School of Pharmacy and Pharmaceutical Science of Mukogawa Women's University in 2014. We started teaching first and second years students according to proficiency from the 2014 academic year. Students were divided into two classes: the regular class (high proficiency class) and the basic class (low proficiency class), based on achievement in several basic subjects related to the study of pharmacy. The staffs in the Pharmaceutical Education Support Center reinforce what is taught to students in the basic class. In this reinforcement method of education, the class size is small, consisting of about 15 students, a quiz to review the previous lesson is given at the beginning of each lecture, and an additional five lectures are conducted, compared to the high proficiency class, which receives 15 lectures. In this study, we evaluated the effects of the reinforcement method of physiology education on achievement in pharmacology that was not conducted in the proficiency-dependent teaching method. The students in the basic class in physiology education were chosen based on achievement levels in anatomy. Achievement levels of pharmacology students in the basic class of physiology improved compared with those of students who had the same achievement levels in physiology but were not taught according to proficiency-dependent teaching in the 2013 academic year. These results suggest that the reinforcement method for education in basic subjects in pharmacy, such as physiology, can improve achievement in more advanced subjects, such as pharmacology.

  1. [Integrative pharmacology: new paradigm of modernization of Chinese medicine].

    Science.gov (United States)

    Xu, Hai-Yu; Yang, Hong-Jun

    2014-02-01

    Chinese medicinal formulae( CMF) were often used in the clinics of traditional Chinese medicine (TCM) which were critical for modernization of Chinese medicine to shed light on the interaction between CMF and biological organisms. In current studies, correlation between system and part, macroscopic actions and microcosmic mechanism, ADME process and pharmacologic actions were often neglected. Thus, we put forward integrative pharmacology, which could integrate the correlation between CMF and biological organisms from multi-levels and multi-dimensional views. Integrative pharmacology would reveal the molecular mechanism of CMF for ailments treatment and screen out effective material systematically, which would be the new paradigm of TCM research.

  2. From action intentions to action effects: how does the sense of agency come about?

    Directory of Open Access Journals (Sweden)

    Valérian eChambon

    2014-05-01

    Full Text Available Sense of agency refers to the feeling of controlling an external event through one’s own action. On one influential view, agency depends on how predictable the consequences of one’s action are, getting stronger as the match between predicted and actual effect of an action gets closer. Thus, sense of agency arises when external events that follow our action are consistent with predictions of action effects made by the motor system while we perform or simply intend to perform an action. According to this view, agency is inferred retrospectively, after an action has been performed and its consequences are known. In contrast, little is known about whether and how internal processes involved in the selection of actions may influence subjective sense of control, in advance of the action itself, and irrespective of effect predictability. In this article, we review several classes of behavioural and neuroimaging data suggesting that earlier processes, linked to fluency of action selection, prospectively contribute to sense of agency. These findings have important implications for better understanding human volition and abnormalities of action experience.

  3. Pharmacological Effects of Active Compounds on Neurodegenerative Disease with Gastrodia and Uncaria Decoction, a Commonly Used Poststroke Decoction

    Directory of Open Access Journals (Sweden)

    Stanley C. C. Chik

    2013-01-01

    Full Text Available Neurodegenerative diseases refer to the selective loss of neuronal systems in patients. The diseases cause high morbidity and mortality to approximately 22 million people worldwide and the number is expected to be tripled by 2050. Up to now, there is no effective prevention and treatment for the neurodegenerative diseases. Although some of the clinical therapies target at slowing down the progression of symptoms of the diseases, the general effectiveness of the drugs has been far from satisfactory. Traditional Chinese medicine becomes popular alternative remedies as it has been practiced clinically for more than thousands of years in China. As neurodegenerative diseases are mediated through different pathways, herbal decoction with multiple herbs is used as an effective therapeutic approach to work on multiple targets. Gastrodia and Uncaria Decoction, a popular TCM decoction, has been used to treat stroke in China. The decoction contains compounds including alkaloids, flavonoids, iridoids, carotenoids, and natural phenols, which have been found to possess anti-inflammatory, antioxidative, and antiapoptotic effects. In this review, we will summarize the recent publications of the pharmacological effects of these five groups of compounds. Understanding the mechanisms of action of these compounds may provide new treatment opportunities for the patients with neurodegenerative diseases.

  4. Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala

    Directory of Open Access Journals (Sweden)

    Iandra Holzmann

    2011-01-01

    Full Text Available There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP, known as “Valeriana del monte”, and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM, forced swimming (FST, strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5% and time spent (44.7% in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.

  5. Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update.

    Science.gov (United States)

    Nassiri-Asl, Marjan; Hosseinzadeh, Hossein

    2016-09-01

    Vitis vinifera fruit (grape) contains various phenolic compounds, flavonoids and stilbenes. In recent years, active constituents found in the fruits, seeds, stems, skin and pomaces of grapes have been identified and some have been studied. In this review, we summarize the active constituents of different parts of V. vinifera and their pharmacological effects including skin protection, antioxidant, antibacterial, anticancer, antiinflammatory and antidiabetic activities, as well as hepatoprotective, cardioprotective and neuroprotective effects in experimental studies published after our 2009 review. Clinical and toxicity studies have also been examined. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Causal binding of actions to their effects.

    Science.gov (United States)

    Buehner, Marc J; Humphreys, Gruffydd R

    2009-10-01

    According to widely held views in cognitive science harking back to David Hume, causality cannot be perceived directly, but instead is inferred from patterns of sensory experience, and the quality of these inferences is determined by perceivable quantities such as contingency and contiguity. We report results that suggest a reversal of Hume's conjecture: People's sense of time is warped by the experience of causality. In a stimulus-anticipation task, participants' response behavior reflected a shortened experience of time in the case of target stimuli participants themselves had generated, relative to equidistant, equally predictable stimuli they had not caused. These findings suggest that causality in the mind leads to temporal binding of cause and effect, and extend and generalize beyond earlier claims of intentional binding between action and outcome.

  7. Motor imagery during action observation modulates automatic imitation effects in rhythmical actions

    Directory of Open Access Journals (Sweden)

    Daniel Lloyd Eaves

    2014-02-01

    Full Text Available We have previously shown that passively observing a task-irrelevant rhythmical action can bias the cycle time of a subsequently executed rhythmical action. Here we use the same paradigm to investigate the impact of different forms of motor imagery (MI during action observation (AO on this automatic imitation (AI effect. Participants saw a picture of the instructed action followed by a rhythmical distractor movie, wherein cycle time was subtly manipulated across trials. They then executed the instructed rhythmical action. When participants imagined performing the instructed action in synchrony with the distractor action (AO + MI, a strong imitation bias was found that was significantly greater than in our previous study. The bias was pronounced equally for compatible and incompatible trials, wherein observed and imagined actions were different in type (e.g., face washing vs. painting or plane of movement, or both. In contrast, no imitation bias was observed when MI conflicted with AO. In Experiment 2, motor execution synchronised with AO produced a stronger imitation bias compared to AO + MI, showing an advantage in synchronisation for overt execution over MI. Furthermore, the bias was stronger when participants synchronised the instructed action with the distractor movie, compared to when they synchronised the distractor action with the distractor movie. Although we still observed a significant bias in the latter condition, this finding indicates a degree of specificity in AI effects for the identity of the synchronised action. Overall, our data show that MI can substantially modulate the effects of AO on subsequent execution, wherein: (1 combined AO + MI can enhance AI effects relative to passive AO; (2 observed and imagined actions can be flexibly coordinated across different action types and planes; and (3 conflicting AO + MI can abolish AI effects. Therefore, combined AO + MI instructions should be considered in motor training and

  8. Botanical characteristics, pharmacological effects and medicinal compo-nents of Korean Panax ginseng C A Meyer

    Institute of Scientific and Technical Information of China (English)

    Kwang-tae CHOI

    2008-01-01

    Korean Panax ginseng C A Meyer is mainly used to maintain the homeostasis of the body, and the pharmacological efficacy of Korean ginseng identified by modern science includes improved brain function, pain-relieving effects, pre-ventive effects against tumors as well as anti-tumor activity, enhanced immune system function, anti-diabetic effects, enhanced liver function, adjusted blood pressure, anti-fatigue and anti-stress effects, improved climacteric disorder and sexual functions, as well as anti-oxidative and anti-aging effects. Further clini-cal studies of these pharmacological efficacies will continue to be carried out. Korean ginseng is found to have such main properties as ginsenoside, ployacety-lene, acid polysaccharide, anti-oxidative aromatic compound, and insulin-like acid peptides. The number of ginsenoside types contained in Korean ginseng (38 ginsenosides) is substantially more than that of ginsenoside types contained in American ginseng (19 ginsenosides). Furthermore, Korean ginseng has been identified to contain more main non-saponin compounds, phenol compounds, acid polysaccharides and polyethylene compounds than American ginseng and Sanchi ginseng.

  9. Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies.

    Science.gov (United States)

    Aurora, Sheena K; Brin, Mitchell F

    2017-01-01

    treatment options for chronic migraine. Of the currently available treatment options, only onabotulinumtoxinA and topiramate have received regulatory approval and have demonstrated efficacy in patients with chronic migraine, although the exact mechanisms of action are not fully elucidated.

  10. String effective actions, dualities, and generating solutions

    NARCIS (Netherlands)

    Chemissany, Wissam Ali

    2008-01-01

    This thesis covers in general two separate topics: the string e®ective actions and the geodesic motion of brane solutions. The main theme of the ¯rst topic, i.e., the string e®ective actions, is the construction of the abelian D-brane e®ective action. In the limit of constant ¯eld strengths this act

  11. Shocking action: Facilitative effects of punishing electric shocks on action control.

    Science.gov (United States)

    Eder, Andreas B; Dignath, David; Erle, Thorsten M; Wiemer, Julian

    2017-08-01

    Four experiments examined motivational effects of response-contingent electric shocks on action initiation. Although the shock was unambiguously aversive for the individual in line with subjective and functional criteria, results showed that the shock-producing action was initiated faster relative to a response producing no shock. However, no facilitation effect was found when strong shocks were delivered, ruling out increased emotional arousal as an explanation. The action was initiated faster even when the response discontinued to generate a shock. Furthermore, a control experiment with affectively neutral vibrotactile stimulations at homologous sites showed an analogous response facilitation effect. Overall, the results contradict the widespread belief that a contingency with a punishing response effect is sufficient for a response suppression. Instead, the results suggest that punishing action effects can facilitate action initiation via anticipatory feedback processes. Implications for theories and applications of punishment are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. 化瘀通闭丸的药理作用及临床应用%Pharmacological Action and Clinical Application of Huayu Tongbi Pill

    Institute of Scientific and Technical Information of China (English)

    郭国富

    2012-01-01

    目的:探讨化疼通闭丸的药理作用和临床应用.方法:结合科研及实际,对化瘀通用丸的药理作用及临床应用进行归纳和总结.结果:化瘀通闭丸具有抗炎消炎、抑菌杀菌、镇痛、提高免疫力等作用,临床用于治疗泌尿系统及生殖系统炎症.结论:化瘀通闭丸治疗泌尿系统及生殖系统炎症疗效确切、安全可靠.%Objective;To investigate the pharmacological effects of huayu tongbi pill in clinical application. Methods:Pharmacological function and clinical application of huayu tongbi pill are summarized combined with scientific research and practice. Results; Huayu tongbi pill has anti - inflammatory, antibacterial sterilization .analgesia and immunity function improvement, the clinic for the treatment of urinary system and reproductive system inflammation. Conclusion;The curative effect of huayu tongbi pill in the treatment of urinary system and reproductive system inflammation is accurate,safe and reliable.

  13. Chemical compsition and pharmacological action of jojoba:research advances%好好芭化学组成及药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    杨雪鸥; 吴然; 张林; 耿红卫

    2014-01-01

    Jojoba(the plant belonging to Simmondsiaceae)seeds are not only a kind of global special oil resources but also a type of good folk medicines because they are riched in jojoba oil and simmondsin and have many pharmacological effects such as anti-inflammatory effect,food inhibitor and promoting-antibiosis. The paper reviews the studies on jojoba chemical compositim, extraction and purification,detection and analysis methods,pharmacological activity and dosage development,in order to provide reference for further research and application.%加州西蒙得木(好好芭)属西蒙得木科植物,其种子不仅是世界特种油料的宝库,也是良好的药用资源,富含好好芭油和西蒙得木素,具有抗炎、减肥以及促抗菌等功效。本文综述了好好芭的药学研究进展,包括化学成分及提取方法、检测方法、药理作用及制剂研究等方面的内容,为好好芭的进一步研究开发提供参考。

  14. Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

    OpenAIRE

    2013-01-01

    We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used ...

  15. The effectiveness of non-pharmacological interventions in older adults with depressive disorders: A systematic review.

    Science.gov (United States)

    Apóstolo, João; Bobrowicz-Campos, Elzbieta; Rodrigues, Manuel; Castro, Inês; Cardoso, Daniela

    2016-06-01

    It is widely acknowledged that mental health disorders are common in older adults and that depression is one of the most serious threats to the mental health of older adults. Although best practice guidelines point out that moderate to severe depression should be approached with pharmacotherapy together with complementary therapies, the use of antidepressant drugs in older adults has various disadvantages, such as long response time, side effects, potential risk of dependency and tolerance, poor compliance rates and high probability of drug interactions. In addition, qualitative studies of depressed people with a chronic illness have indicated that both patients and healthcare professionals prefer a psychosocial treatment for depression over a pharmacological one. This review aimed to identify and synthesize the best available evidence related to the effectiveness of non-pharmacological interventions for older adults with depressive disorders. Systematic review of studies with any experimental design considering non-pharmacological interventions for older adults with depressive disorders. An initial search of MEDLINE and CINAHL was undertaken, followed by a second search for published and unpublished studies, from January 2000 to March 2012, of major healthcare-related electronic databases. Studies in English, Spanish and Portuguese were included in the review. This review considered studies that included adult patients, aged over 65 years with any type of depressive disorder, regardless of comorbidities and any previous treatments, but excluded those with manic or psychotic episodes/symptoms. All studies that met the inclusion criteria were assessed for methodological quality by two independent reviewers using a standardized critical appraisal checklist for randomized and quasi-randomized controlled studies from the Joanna Briggs Institute. Data extraction was also conducted by two independent reviewers based on the Joanna Briggs Institute data extraction form for

  16. The effective action in four-dimensional CDT

    CERN Document Server

    Gizbert-Studnicki, Jakub

    2015-01-01

    We present recent results concerning the measurement and analysis of the effective action in four-dimensional Causal Dynamical Triangulations. The action describes quantum fluctuations of the spatial volume of the CDT universe (or alternatively the scale factor) after integrating out other degrees of freedom. We use the covariance of volume fluctuations to measure and parametrize the effective action inside the de Sitter phase, also called the C phase. We show that the action is consistent with a simple discretization of the minisuperspace action (with a reversed overall sign). We discuss possible subleading corrections and show how to construct a more complicated effective action comprising both integer and half-integer discrete proper time layers. We introduce a new method of the effective action measurement based on the transfer matrix. We show that the results of the new method are fully consistent with the covariance matrix method inside the de Sitter phase. We use the new method to measure the effective...

  17. Acute Stressor Effects on Goal-Directed Action in Rats

    Science.gov (United States)

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  18. Acute Stressor Effects on Goal-Directed Action in Rats

    Science.gov (United States)

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  19. [Pharmacological effects of the combination of a spasmolytic (otilonium) with a benzodiazepine (diazepam)].

    Science.gov (United States)

    Coruzzi, G; Adami, M; Poli, E; Signorini, G; Bertaccini, G

    1982-01-01

    The pharmacological effects of an association represented by a myolitic agent (otilonium bromide) and a benzodiazepine (diazepam) were investigated on different in vitro preparations and on one in vivo test. In the isolated preparations both drugs administered alone showed a remarkable inhibitory effect on the motility of different areas of the digestive system both spontaneous and evoked by different stimulatory agents. Association of the two compounds gave rise to additive effects or actually to a potentiating effect according to the different tissues and animal species. Negative interference was never observed. The same was true also in the in vivo preparation ("in situ" rat pylorus). The significance and the importance of these observations are discussed also in the light of the relevant clinical implications.

  20. Modulation of the Pharmacological and Biochemical Actions of Leiurusquinquestriatus (L.q) Scorpion Venom by Exposure to Gamma Radiation

    OpenAIRE

    Heba A. Mohamed*, Esmat A. Shaaban* , Aber M Amin** and Sanaa A. Kenawy

    2011-01-01

    This study was undertaken to evaluate the effect of gamma radiation (1.5 KGy & 3 KGy) on L.q scorpion venom. This was carried out by studying the toxicological, biochemical & immunological properties of the venom before and after exposure to gamma radiation. Material and methods Animals, venom, antivenin, gamma radiation, 125I. Results Data revealed that the toxicity of irradiated venom (1.5 KGy & 3 KGy) decreased as compared to that of the native one. LD50 of irradiated venom were 3.5 mg/kg ...

  1. Pharmacological treatment of mechanical edema: a randomized controlled trial about the effects of mesoglycan.

    Science.gov (United States)

    Viliani, T; Scarselli, M; Pieri, A; Gatti, M; Santini, M; Pasquetti, P

    2009-03-01

    Mechanical edema (MO) is frequently found in a lot of the lower extremities' orthopedic diseases. In absence of deep vein thrombosis, MO is caused by the change in the dynamics of calf muscle pump with venous hypertension and by the change in capillary permeability which offsets the extra-vascular fluid balance resulting in edema formation. The correct treatment includes specific training for musculo-skeletal and gait recovery, together with medical treatment focused on venous endothelium. Little information is available about pharmacological treatment of this condition. Some studies suggest the efficacy of mesoglycan in venous pathology. Aim of this study was to evaluate the clinical efficacy of the pharmacological treatment (mesoglycan 50 mg p.o., twice a day) in patients affected by MO. Forty-four patients with MO, aged 20-89 years, were randomized in two treatment groups: specific physiotherapy (Fkt) alone or physiotherapy plus mesoglycan 50 mg twice a day, per os. The patients were evaluated before treatment (t0), and after 1 month of treatment (t1), measuring ankle joint range of motion (degrees), calf circumference and malleolar circumference (cm), pain Borg CR10 Scale and adapted lymphedema Weiss Scale. Statistical analysis was performed by the Pearson's c2 test and the Mann-Whitney-Wilcoxon test. At the final evaluation of the objective and subjective parameters, the mesoglycan effect combined to the Fkt provided statistical differences on nearly all the parameters in comparison with the patients randomised to Fkt alone. The present study suggest that mesoglycan treatment (50 mg p.o., twice a day) can improve the recovery of MO, and it is well tolerated by the patients. Specific physiotherapy remains the first treatment for the recovery of both muscular pump and correct walking, but the optimal treatment of MO seems to be a synergic approach, including both pharmacological and mobilization programs.

  2. Pharmacological and genetic manipulation of kappa opioid receptors: effects on cocaine- and pentylenetetrazol-induced convulsions and seizure kindling.

    Science.gov (United States)

    Kaminski, Rafal M; Witkin, Jeffrey M; Shippenberg, Toni S

    2007-03-01

    The present study used pharmacological and gene ablation techniques to examine the involvement of kappa opioid receptors (KOPr) in modulating the convulsant effects of two mechanistically different drugs: cocaine and pentylenetetrazol (PTZ; GABA-A receptor antagonist) in mice. Systemic administration of the selective KOPr-1 agonist, U69593 (0.16-0.6mg/kg; s.c.), failed to modify cocaine-evoked convulsions or cocaine kindling. Similarly, no alteration in responsiveness to cocaine was observed in wild-type mice that received the selective KOPr-1 antagonist, nor-binaltorphimine (nor-BNI; 5mg/kg) or in mice lacking the gene encoding KOPr-1. In contrast to cocaine, U69593 attenuated the seizures induced by acute or repeated PTZ administration. Nor-BNI decreased the threshold for PTZ-evoked seizures and increased seizure incidence during the initial induction of kindling relative to controls. Decreased thresholds for PTZ-induced seizures were also observed in KOPr-1 knock out mice. Together, these data demonstrate an involvement of endogenous KOPr systems in modulating vulnerability to the convulsant effects of PTZ but not cocaine. Furthermore, they demonstrate that KOPr-1 activation protects against acute and kindled seizures induced by this convulsant. Finally, the results of our study suggest that KOPr-1 antagonists will not have therapeutic utility against cocaine-induced seizures, while they may prove beneficial in attenuating several actions of cocaine that have been linked to its abuse.

  3. Action-effect congruence during observational learning leads to faster action sequence learning.

    Science.gov (United States)

    Horvath, Jared C; Gray, Zachary; Schilberg, Lukas; Vidrin, Ilya; Pascual-Leone, Alvaro

    2015-01-01

    Common coding theory suggests that any action (pressing a piano key) is intimately linked with its resultant sensory effect (an auditory musical tone). We conducted two experiments to explore the effect of varying auditory action-effect patterns during complex action learning. In Experiment 1, participants were assigned to 1 of 4 groups, watched a silent video of a hand playing a sequence on a piano keyboard with no auditory action effect (observation) and were asked to practise and perform the sequence on an identical keyboard with varying action effects (reproduction). During reproduction, Group 1 heard no auditory tones (identical to observed video), Group 2 heard typical scale-ascending piano tones with each key press, Group 3 heard fixed but out-of-sequence piano tones with each key press, and Group 4 heard random piano tones with each key press. In Experiment two, new participants were assigned to 1 of 2 groups and watched an identical video; however, the video in this experiment contained typical, scale-ascending piano sounds. During reproduction, Group 1 heard no auditory tones while Group 2 heard typical, scale-ascending piano tones with each key press (identical to observed video). Our results showed that participants whose action-effect patterns during reproduction matched those in the observed video learned the action sequence faster than participants whose action-effect patterns during reproduction differed from those in the observed video. Additionally, our results suggest that adding an effect during reproduction (when one is absent during observation) is somewhat more detrimental to action sequence learning than removing an effect during reproduction (when one is present during observation).

  4. Pharmacological mechanisms underlying the antinociceptive and tolerance effects of the 6,14-bridged oripavine compound 030418

    Institute of Scientific and Technical Information of China (English)

    Quan WEN; Gang YU; Yu-lei LI; Ling-di YAN; Ze-hui GONG

    2011-01-01

    Aim:To investigate possible pharmacological mechanisms underlying the antinociceptive effect of and tolerance to N-methyl-7α-[(R)-1-hydroxy-1-methyl-3-(thien-3-yi)-propyl]-6,14-endo-ethanotetrahydronororipavine (030418),a derivative of thienorphine.Methods:The binding affinity and efficacy of 030418 were determined using receptor binding and guanosine 5'-0-(3-[35S]thio)triphosphate ([35S]GTPyS) assays in CHO-μ,CHO-κ,CHO-δ,and CHO-ORL1 cell membranes.The analgesic activity of and tolerance to 030418 were evaluated in thermal nociceptive tests in mice.The effects of 030418 on opioid receptors were further investigated using in vivo pharmacological antagonist blockade and in vitro tissue preparations.Results:The compound 030418 displayed high binding affinity to all subtypes of opioid receptors with Ki values in the nanomolar range.In [35S]GTPyS binding assay,the maximal stimulation of 030418 to μ-,κ-,δ-receptors and the ORL1 receptor was 89%,86%,67% and 91%,respectively.In hot-plate test,the antinociceptive effect of 030418 was more potent and longer than morphine.The nonselective opioid receptor antagonist naloxone could completely block 030418-induced antinociception,while both the μ-opioid receptor antagonist β-FNA and the κ-opioid receptor antagonist nor-BNI attenuated 030418-induced antinociception.In contrast,the ORL1 receptor antagonist J-113397 enhanced the antinociceptive effect of 030418.Additionally,chronic treatment with 030418resulted in a dramatic development of tolerance that could not be effectively prevented by J-113397.In guinea pig ileum preparation,the existing action of 030418 could be removed with difficulty after prolonged washing.Conclusion:The compound 030418 is a novel agonist of opioid receptors with high efficiency,long-lasting effect and liability to tolerance,which may be closely correlated with the methyl group at the N17 position and the high hydrophobicity of the C7-thiophene group in its chemical structure.

  5. [The role of the substantia nigra in the anticonvulsive and antiaggressive effects of diazepam during pharmacological kindling].

    Science.gov (United States)

    Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Makul'kin, R F

    1990-01-01

    The seizure activity was investigated on the model of pharmacological kindling which was induced by repeated picrotoxin injections in the subthreshold dose, after the tryptic fragment of T5 protein-human diazepam binding inhibitor (DBI) (10 micrograms) injection into a reticular part of substantia nigra. An increase in the seizure reaction and suppression of the antiseizure diazepam action were observed. Intranigral DBI injection induced no change in a threshold of "attacks" in rats which were induced through electric shocks delivered to animals with an electrode floor and no changes in antiaggressive diazepam action were observed under such conditions.

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

    Science.gov (United States)

    Kenakin, Terry; Christopoulos, Arthur

    2011-04-01

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

  7. Effects of social intention on movement kinematics in cooperative actions

    Directory of Open Access Journals (Sweden)

    Francois eQuesque

    2013-10-01

    Full Text Available Optimal control models of biological movements are used to account for those internal variables that constrain voluntary goal-directed actions. They however do not take into account external environmental constraints as those associated to social intention. We investigated here the effects of the social context on kinematic characteristics of sequential actions consisting in placing an object on an initial pad (preparatory action before reaching and grasping as fast as possible the object to move it to another location (main action. Reach-to-grasp actions were performed either in an isolated condition or in the presence of a partner (audience effect, located in the near or far space (effect of shared reachable space, and who could intervene on the object in a systematic fashion (effect of social intention effect or not (effect of social uncertainty. Results showed an absence of audience effect but nevertheless an influence of the social context both on the main and the preparatory actions. In particular, a localized effect of shared reachable space was observed on the main action, which was smoother when performed within the reachable space of the partner. Furthermore, a global effect of social uncertainty was observed on both actions with faster and jerkier movements. Finally, social intention affected the preparatory action with higher wrist displacements and slower movements when the object was placed for the partner rather than placed for self-use. Overall, these results demonstrate specific effects of action space, social uncertainty and social intention on the planning of reach-to-grasp actions, in particular on the preparatory action, which was performed with no specific execution constraint. These findings underline the importance of considering the social context in optimal models of action control for human-robot interactions, in particular when focusing on the implementation of motor parameters required to afford intuitive

  8. Tetrahydrobiopterin, its mode of action on phenylalanine hydroxylase, and importance of genotypes for pharmacological therapy of phenylketonuria.

    Science.gov (United States)

    Heintz, Caroline; Cotton, Richard G H; Blau, Nenad

    2013-07-01

    In about 20%-30% of phenylketonuria (PKU) patients (all phenotypes of PAH deficiency), Phe levels may be controlled through phenylalanine hydroxylase cofactor tetrahydrobiopterin therapy. These patients can be diagnosed by an oral tetrahydrobiopterin challenge and are characterized by mutations coding for proteins with substantial residual PAH activity. They can be treated with a commercially available synthetic form of tetrahydrobiopterin, either as a monotherapy or as adjunct to the diet. This review article summarizes molecular and metabolic bases of PKU and the importance of the tetrahydrobiopterin loading test used for PKU patients. On the basis of in vitro residual PAH activity, more than 1,200 genotypes from patients challenged with tetrahydrobiopterin were categorized as predictive for tetrahydrobiopterin responsiveness or non-responsiveness and correlated with the loading test, phenotype, and residual in vitro PAH activity. The coexpression of two distinct PAH mutant alleles revealed possible dominance effects (positive or negative) by one of the mutations on residual activity as result of interallelic complementation. The treatment of the transfected cells with tetrahydrobiopterin showed an increase in residual PAH activity with several mutations coexpressed.

  9. Possible Pharmacological Basis for Antithrombotic Effect of Glycyrrhiza Glabra in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jain M.

    2009-07-01

    Full Text Available It has been previously identified that 3-aryl comarin derivative, GU-7 isolated from Liquorice posses Antiplatelet activity. It inhibits platelet aggregation by increasing intraplatelet cyclic AMP concentration. Here we report the in-vivo effects of extract of Glycyrrhiza glabra and also the combined effect with Vitamin K and Heparin. Extract of Glycyrrhiza glabra increased the bleeding time when given in the doses of 180 mg/kg and 360 mg/kg. Blood loss was evaluated 60 minute later as a function of absorbance at 540 nm due to hemoglobin content in water solution. Altogether data indicates that Glycyrrhiza glabra is an effective anti thrombotic agent in vivo, which may account for its known pharmacological properties.

  10. Systematic review of the effectiveness of pharmacological treatments for adolescents and adults with autism spectrum disorder.

    Science.gov (United States)

    Broadstock, Marita; Doughty, Carolyn; Eggleston, Matt

    2007-07-01

    The variable expression of autism over the lifespan is likely to lead to different symptoms and support requirements, and to distinct responses to pharmacotherapy treatment, in older patients compared to children. This systematic review considers the effectiveness of pharmacological treatment in managing autism spectrum disorder in adolescents and adults. Following a comprehensive search of literature published in English from 1980, methodological criteria were applied to identify studies designed to reliably assess treatment effectiveness. Only five double-blind, randomized controlled trials were eligible for appraisal. All had small sample sizes (mean = 30) and brief treatment duration of no more than 12 weeks. The paucity of trials and their methodological limitations means that there is only preliminary evidence about the short-term effectiveness of a few drug treatments for this age group. There was also a lack of reliable data reported on drug safety profiles. Methodological challenges and directions for future research are discussed.

  11. Principles of safety pharmacology.

    Science.gov (United States)

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

    2008-08-01

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

  12. On the calculation of effective actions by string methods

    CERN Document Server

    Schmidt, M G

    1993-01-01

    Strassler's formulation of the string-derived Bern-Kosower formalism is reconsidered with particular emphasis on effective actions and form factors. Two- and three point form factors in the nonabelian effective action are calculated and compared with those obtained in the heat kernel approach of Barvinsky, Vilkovisky et al. We discuss the Fock-Schwinger gauge and propose a manifestly covariant calculational scheme for one-loop effective actions in gauge theory.

  13. A convergent series for the QED effective action.

    Science.gov (United States)

    Cho, Y M; Pak, D G

    2001-03-05

    The one-loop effective action of QED obtained by Heisenberg and Euler and by Schwinger has been expressed by an asymptotic perturbative series which is divergent. In this Letter we present a nonperturbative but convergent series of the effective action. With the convergent series we establish the existence of the manifest electric-magnetic duality in the one-loop effective action of QED.

  14. Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology.

    Science.gov (United States)

    Csoka, Antonei B; Szyf, Moshe

    2009-11-01

    The term "Epigenetics" refers to DNA and chromatin modifications that persist from one cell division to the next, despite a lack of change in the underlying DNA sequence. The "epigenome" refers to the overall epigenetic state of a cell, and serves as an interface between the environment and the genome. The epigenome is dynamic and responsive to environmental signals not only during development, but also throughout life; and it is becoming increasingly apparent that chemicals can cause changes in gene expression that persist long after exposure has ceased. Here we present the hypothesis that commonly-used pharmaceutical drugs can cause such persistent epigenetic changes. Drugs may alter epigenetic homeostasis by direct or indirect mechanisms. Direct effects may be caused by drugs which affect chromatin architecture or DNA methylation. For example the antihypertensive hydralazine inhibits DNA methylation. An example of an indirectly acting drug is isotretinoin, which has transcription factor activity. A two-tier mechanism is postulated for indirect effects in which acute exposure to a drug influences signaling pathways that may lead to an alteration of transcription factor activity at gene promoters. This stimulation results in the altered expression of receptors, signaling molecules, and other proteins necessary to alter genetic regulatory circuits. With more chronic exposure, cells adapt by an unknown hypothetical process that results in more permanent modifications to DNA methylation and chromatin structure, leading to enduring alteration of a given epigenetic network. Therefore, any epigenetic side-effect caused by a drug may persist after the drug is discontinued. It is further proposed that some iatrogenic diseases such as tardive dyskinesia and drug-induced SLE are epigenetic in nature. If this hypothesis is correct the consequences for modern medicine are profound, since it would imply that our current understanding of pharmacology is an oversimplification

  15. Effectiveness of an audience response system in teaching pharmacology to baccalaureate nursing students.

    Science.gov (United States)

    Vana, Kimberly D; Silva, Graciela E; Muzyka, Diann; Hirani, Lorraine M

    2011-06-01

    It has been proposed that students' use of an audience response system, commonly called clickers, may promote comprehension and retention of didactic material. Whether this method actually improves students' grades, however, is still not determined. The purpose of this study was to evaluate whether a lecture format utilizing multiple-choice PowerPoint slides and an audience response system was more effective than a lecture format using only multiple-choice PowerPoint slides in the comprehension and retention of pharmacological knowledge in baccalaureate nursing students. The study also assessed whether the additional use of clickers positively affected students' satisfaction with their learning. Results from 78 students who attended lecture classes with multiple-choice PowerPoint slides plus clickers were compared with those of 55 students who utilized multiple-choice PowerPoint slides only. Test scores between these two groups were not significantly different. A satisfaction questionnaire showed that 72.2% of the control students did not desire the opportunity to use clickers. Of the group utilizing the clickers, 92.3% recommend the use of this system in future courses. The use of multiple-choice PowerPoint slides and an audience response system did not seem to improve the students' comprehension or retention of pharmacological knowledge as compared with those who used solely multiple-choice PowerPoint slides.

  16. 迷迭香活性提取物的药理作用研究进展%Research progress on pharmacological action of rosemary active extract

    Institute of Scientific and Technical Information of China (English)

    周慧灵; 梁婉娴; 徐道立; 陈雨; 王莹; 赵丕文

    2015-01-01

    Rosemary is a widely used traditional Chinese herb, which has the effects of tranquillization, regulating stomach and so on. At present, researches in vivo and vitro show that rosemary active extract has many significant pharmacological effects such as anti-oxidation, inhibiting the proliferation of hepatoma carcinoma cells and mammary carcinoma cells, inhibiting the growth of escherichia coli, staphylococcus aureus and plant pathogenic fungi, anti-virus, anti-inflammation, inducing T cell activation, anti-angiogenesis and so on. Meanwhile, rosemary active extract can be used in the treatment of Parkinson' s disease, Alzheimer disease and vascular dementia. By referring to the literatures and information both at home and abroad, this article summarizes the pharmacological function and mechanism of rosemary active extract.%迷迭香是一种广泛使用的中草药,具有安神、健胃等功效. 目前,体内外的研究表明,迷迭香活性提取物具有抗氧化,抑制肝癌细胞、乳腺癌细胞增殖,抑制大肠杆菌、金黄色葡萄球菌、植物病原真菌生长等作用,还具有抗病毒、抗炎、诱导T细胞活化,抗血管形成等作用,对帕金森病、阿尔茨海默病、血管性痴呆也有一定的治疗作用. 文章通过查阅国内外资料,对迷迭香活性提取物的药理作用及其机制的研究进展进行综述.

  17. [Effect of pharmacologic treatment of the nutritional status of neurologic patients].

    Science.gov (United States)

    Piñeiro Corrales, Guadalupe; Vázquez López, Cristina; Álvarez Payero, Miriam

    2014-01-01

    Clinical manifestations accompanying neurological diseases are diverse and affect multiple organs. Nutritional status of patients with certain neurological diseases such as stroke, Alzheimer's disease, Parkinson's disease, Epilepsy and Multiple Sclerosis can be altered because of symptoms associated with disease course, including certain micronutrient deficiency (folic acid, zinc, vitamin B6 and B12, vitamin D, vitamin E and vitamin C), changes in energy expenditure, intake decreased, gastrointestinal disorders and dysfunction of the bone mass. Also, we have to take in account other factors as: advanced age, multiple co morbidities, polypharmacy, the use of herbal products, social habits, diet and pharmacological treatments effect. An assessment of the factors related to neurological treatment that cause alterations in metabolic and nutritional status was performed: side effects of anti-Parkinson drugs, antiepileptic drugs, and multiple sclerosis drugs; drug-nutrient interactions; and nutrient-drug interactions.

  18. Metabolomics of Methylphenidate and Ethylphenidate: Implications in Pharmacological and Toxicological Effects.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2017-02-01

    Methylphenidate (MPH) is primarily indicated for attention-deficit hyperactivity disorder and narcolepsy therapy. A marked individual variability in the dose-response has been observed, and therefore dosage must be titrated for optimal therapeutic effect with minimal toxicity. This variability has been claimed to be predominantly pharmacokinetic. Moreover, due to its similar pharmacodynamics to amphetamine, MPH has been abused and fatalities have been reported. This review aims to discuss metabolomics of MPH, namely by presenting all major and minor metabolites. Ritalinic acid is the main metabolite. In addition, minor pathways involving aromatic hydroxylation, microsomal oxidation and conjugation have also been reported to form the p-hydroxy-, oxo- and conjugated metabolites, respectively. MPH may undergo transesterification with ethanol producing ethylphenidate, which is also pharmacologically active. It is expected that knowing the metabolomics of MPH may provide further insights regarding individual contribution for MPH pharmacodynamics and toxicological effects, namely if ethanol is co-consumed.

  19. [Effectiveness of occupational therapy and other non-pharmacological therapies in cognitive impairment and Alzheimer's disease].

    Science.gov (United States)

    Matilla-Mora, Rosa; Martínez-Piédrola, Rosa María; Fernández Huete, Javier

    A review is presented on the existing knowledge about the usefulness of the occupational therapy in the non-pharmacological treatment of Alzheimer's disease. After conducting a literature search of the period 2010-2015, 25 articles that met the inclusion criteria were selected. The evidence obtained showed the efficiency and effectiveness of OT in delaying the progression of various disorders, especially when structured home OT programs are used. These programs should include aerobic and strengthening, sensory stimulation, and cognitive and memory training exercises based on learning without mistakes. These have shown benefits in the performance of activities of daily living, cognitive and emotional functioning. The importance is stressed of the combined and individual household level intervention and caregiver education. Finally, the need for more studies on the effectiveness of long-term sensory stimulation is highlighted. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. The effectiveness of non-pharmacological pain management in relieving chronic pain for children and adolescents.

    Science.gov (United States)

    Mu, Pei-Fan; Chen, Yu-Chih; Cheng, Shu-Chen

    2009-01-01

    There is accumulating evidence that recurring pain symptoms in children are becoming a serious health concern. Children and adolescents who suffer from ongoing pain have negative outcomes not only to their physical health, but also to their emotional and spiritual health. Furthermore, recurrent pain in children may also cause a number of other negative consequences to the child, the family and society. Thus, a non-pharmacological approach to reduce the pain is vital to help children having better quality of life. The objective of this review is to determine the best available evidence on the effectiveness of non-pharmacological pain management in relieving chronic pain for children and adolescents. The search strategy aimed to find published studies, between 1956 and 2008 and limited to the English or Chinese languages. Reference lists of studies that met the inclusion criteria were searched for additional studies. This review included any systematic reviews, randomized controlled trials and quasi-experimental design that explored the effectiveness of non-pharmacological intervention for chronic pain in children and adolescents. Children and adolescents with cancer pain, Juvenile chronic arthritis, sickle cell disease, burn pain, chronic or recurrent abdominal pain, headache and aged 18 years old or less and suffering with pain for at least one month. The review considered studies that examined non-pharmacological interventions in relieving chronic pain for children and adolescents that included heat wrap therapy, massage, chiropractic spinal manipulative therapy, cognitive-behavioral therapy (distraction & guided imagery), meditation, progressive muscle relaxation, self-hypnosis, biofeedback, music therapy, and dance training. The primary outcome measures included: (1) Behavioral variables, such as pain behavior, cognitive coping and appraisal, psychiatric reaction (anxiety and depression), and social activities, (2) Quality of life scores and (3) Pain scores. The

  1. Pharmacological Action of Adenophora Polysaccharides

    Institute of Scientific and Technical Information of China (English)

    李泱; 李春红; 唐富天; 李新芳

    2004-01-01

    Adenophora polysaccharides (AP), is an active principle extracted from the root of Adenophorae Potaninii Korsh originated in Gansu Province and isolated with boiling water. AP is isolated and purified from the crude drug by DEAE-cellulose and Sephadex G-200 column, with a white powder and mean molecular weight of 8.3×104 , and [α]D20 of AP is + 68. AP is only composed of glucose judging from the analysis of it with patina chromatography (PC) and gas chromatography-mass spectrometer (GC-MS) methods.

  2. Pharmacological Action of Adenophora Polysaccharides

    Institute of Scientific and Technical Information of China (English)

    李泱; 李春红; 唐富天; 李新芳

    2004-01-01

    @@ Adenophora polysaccharides (AP), is an active principle extracted from the root of Adenophorae Potaninii Korsh originated in Gansu Province and isolated with boiling water(1). AP is isolated and purified from the crude drug by DEAE-cellulose and Sephadex G-200 column, with a white powder and mean molecular weight of 8.3 × 104 , and [α]D20of AP is + 68(1). AP is only composed of glucose judging from the analysis of it with patina chromatography (PC) and gas chromatography-mass spectrometer (GC-MS) methods.The methylation analysis showed that AP is composed of (1→6) linked glucose residues. The measure of nuclear magnetic resonance imaging (NMR) 1H NMR and 14C NMR techniques further proved that AP is α(l→6) linked by Dglucose. The structure of AP is as follows: -[→6]α-D-Glu(1-)n→ (2).

  3. Endocannabinoids and Their Pharmacological Actions.

    Science.gov (United States)

    Pertwee, Roger G

    2015-01-01

    The endocannabinoid system consists of G protein-coupled cannabinoid CB(1) and CB(2) receptors, of endogenous compounds known as endocannabinoids that can target these receptors, of enzymes that catalyse endocannabinoid biosynthesis and metabolism, and of processes responsible for the cellular uptake of some endocannabinoids. This review presents in vitro evidence that most or all of the following 13 compounds are probably orthosteric endocannabinoids since they have all been detected in mammalian tissues in one or more investigation, and all been found to bind to cannabinoid receptors, probably to an orthosteric site: anandamide, 2-arachidonoylglycerol, noladin ether, dihomo-γ-linolenoylethanolamide, virodhamine, oleamide, docosahexaenoylethanolamide, eicosapentaenoylethanolamide, sphingosine, docosatetraenoylethanolamide, N-arachidonoyldopamine, N-oleoyldopamine and haemopressin. In addition, this review describes in vitro findings that suggest that the first eight of these compounds can activate CB(1) and sometimes also CB(2) receptors and that another two of these compounds are CB(1) receptor antagonists (sphingosine) or antagonists/inverse agonists (haemopressin). Evidence for the existence of at least three allosteric endocannabinoids is also presented. These endogenous compounds appear to target allosteric sites on cannabinoid receptors in vitro, either as negative allosteric modulators of the CB1 receptor (pepcan-12 and pregnenolone) or as positive allosteric modulators of this receptor (lipoxin A(4)) or of the CB(2) receptor (pepcan-12). Also discussed are current in vitro data that indicate the extent to which some established or putative orthosteric endocannabinoids seem to target non-cannabinoid receptors and ion channels, particularly at concentrations at which they have been found to interact with CB(1) or CB(2) receptors.

  4. Foundation ActionScript 30 Image Effects

    CERN Document Server

    Yard, Todd

    2009-01-01

    Flash has always been a tool for delivering compelling and unique experiences through dynamic visual presentation. The Flash platform has grown to include application development in Flex, video streaming with the Flash Media Server, and desktop delivery through AIR, but all of that content still comes down to pixels on the screen, and all of those pixels can be manipulated through the power of the ActionScript language. In this book, you will find in-depth coverage of the graphics capabilities of ActionScript 3.0: the enhanced drawing API in Flash Player 10 that allows you to draw vector shape

  5. Comparative study on pharmacological effects of DM-phencynonate hydrochloride and its optical isomers

    Institute of Scientific and Technical Information of China (English)

    Li-yun WANG; Jian-quan ZHENG; Yun WANG; Bo-hua ZHONG; Jin-xiu RUAN; Ke-liang LIU

    2005-01-01

    Aim: The 3 -azabicyclo(3,3, 1)nonanyl-9-α-yl-α-cyclopentyl-α-phenyl-α-glycolate (DM-phencynonate hydrochloride, DMCPG) is a demethylated metabolite of 3-methyl-3-azabicyclo(3,3,1)nonanyl-9-α-yl-α-cyclopentyl-α-phenyl-α-glycolate (phencynonate hydrochloride, CPG). (±)DMCPG had one chiral center and two enantiomers [R(-) and S(+)DMCPG]. Here we carried out a comparative study of the pharmacological profiles of these optical isomers. Methods: Affinity and relative efficacy were tested using a radioligand-binding assay with muscarinic acetylcholine receptors from the rat cerebral cortex. Pharmacological activity was assessed in three individual experiments: (1) potentiating the effect of a subthreshold hypnotic dose of sodium pentobarbital; (2) inhibiting oxotremorineinduced salivation; and (3) inhibiting the contractile response to carbachol.Results: In the competitive binding assay, R(-)DMCPG (Ki=763.75 nmol/L) was 4-and 2-fold more potent than (±)DMCPG (Ki=3186 nmol/L) and S(+)DMCPG (Ki= 1699 nmol/L) in inhibiting the binding of [3H]QNB. The R(-) and S (+) configurations showed positive cooperation (nH>1) with the muscarinic receptor, whereas (±)DMCPG had a negative cooperation (nH<1) relationship with the muscarinic receptor in a radio-binding assay. Both the R(-) and S(+) configurations could potentiate the effect of sub-threshold hypnotic dose of sodium pentobarbital in a dose-dependent manner (the ED50 values were 2.53 and 18.65 mg/kg, respectively),but (±)DMCPG did not display significant central depressant effects at doses from 10 to 29.15 mg/kg (P>0.05). (±)DMCPG and its optical isomers suppressed the guinea pig ileum contractile response to carbachol. The IC50 values were 7.78×10-9,1.88×10-7, and 1.03× 10-7 nmol/L, respectively. In the anti-salivation study,(±)DMCPG and its enantiomers depressed oxotremorine- induced salivation in a dose-dependent manner, and the order of potency was R(-)DMCPG (ED50=0.44 mg/kg)>(±)DMCPG (ED50

  6. Research advances intriterpenoids constituents and pharmacological action of Boswellia carterii%乳香中三萜类化合物和药理活性的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙妍; 商庆辉

    2016-01-01

    In this study, the recent progress in the research of triterpenoids and pharmacological activities of frankincense, the gum resin of Boswellia carterii or the other plants to the same species mainly consisting of chemical constituents, such as pentacyclic triterpenoid and tetracyclic triterpenoid, was reviewed. Investigations demonstrated that resin had the following pharmacological effects: anti-inflammatory, antitumor, inducing differentiation and apoptosis, anti-ulcer, hypoglycemic action, improvement on learning and memory, etc. The results also indicated that fewer adverse reactions and potential medicinal value of this material. The research will provide reference for further research of Boswellia carterii.%乳香为橄榄科植物乳香树或同属植物的胶状树脂,主要活性成分为五环三萜、四环三萜等三萜类化合物。现代药理研究表明乳香有抗炎、抗肿瘤、诱导分化凋亡、抗溃疡、降糖、改善学习记忆等药理活性,在抗炎、抗肿瘤方面药理研究较为深入,不良反应少,有潜在的药用价值。通过查阅文献,对近五年来乳香三萜类成分及其药理作用研究进展进行综述,为乳香的进一步研究提供参考。

  7. Action-specific effects in perception and their potential applications

    OpenAIRE

    Witt, Jessica K.; Linkenauger, Sally; Wickens, Chris

    2016-01-01

    Spatial perception is biased by action. Hills appear steeper and distances appear farther to individuals who would have to exert more effort to transverse the space. Objects appear closer, smaller, and faster when they are easier to obtain. Athletes who are playing better than others see their targets as bigger. These phenomena are collectively known as action-specific effects on perception. In this target article, we review evidence for action-specific effects, including evidence that they r...

  8. Effective Action and Schwinger Pair Production in Strong QED

    CERN Document Server

    Kim, Sang Pyo

    2009-01-01

    Some field theoretical aspects, such as the effective action and Schwinger pair production, are critically reviewed in strong QED. The difference of the boundary conditions on the solutions of the field equation is discussed to result in the effective action both in the Coulomb and time-dependent gauge. Finally, the apparent spin-statistics inversion is also discussed, where the WKB action for bosons (fermions) works well for fermion (boson) pair-production rate.

  9. Effective action for supersymmetric chiral anomaly

    Energy Technology Data Exchange (ETDEWEB)

    Krivoshchekov, V.K.; Chekhov, L.O.

    1987-05-01

    It is shown that consistency conditions of the type of the Wess-Zumino conditions are necessary and sufficient conditions for local integrability of the supersymmetric chiral anomaly. It follows from the requirement of global integrability that the coefficient of the anomalous action is discrete. Explicit expressions are obtained for consistent anomalies and the corresponding functionals, which depend on superfields of various types.

  10. Research progress on pharmacologic actions of salvianolic acid B%丹酚酸B药理作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    赵先; 王婧雯; 陆杨; 廖悠悠; 徐焕春; 白娟; 封小娜; 贾艳艳; 爱东

    2015-01-01

    目的:为丹酚酸B的进一步研究提供参考,为其临床合理利用和开发提供科学依据。方法检索中国知网、万方医学网、PubM ed至2012年收载的公开发表的有关丹酚酸B的研究文献,进行综述,对丹酚酸B的药理作用进行整理、归纳、分析。结果与结论丹酚酸B是丹参的主要有效水溶性成分,它具有清除氧自由基、抗氧化、抗炎、抗纤维化等药理作用,对心脑血管系统、肝脏、肾脏、肺都有保护作用,同时还有一定抗肿瘤活性。%Objective To provide reference for salvianolic acid B′s further study and to provide evidence for its clinical usage and fur‐ther developing .Methods The original articles ,which were retrieved from Chinese Hownet ,Wanfang Medical Network ,as well as PubMed ,were reviewed .The pharmacological actions of salvianolic acid B were sorted ,generalized and analyzed .Results and Conclusion Salvianolic acid B as one of the main water‐soluble components of Radix salviae can be used to protect the cardio‐ce‐rebrovascular system ,liver ,kidney ,lung by eliminating oxygen radicals and other mechanism .

  11. Effective action and semiclassical limit of spin foam models

    CERN Document Server

    Mikovic, A

    2011-01-01

    We define an effective action for spin foam models of quantum gravity by adapting the background field method from quantum field theory. We show that the Regge action is the leading term in the semi-classical expansion of the spin foam effective action if the vertex amplitude has the large-spin asymptotics which is proportional to an exponential function of the vertex Regge action. In the case of the known three-dimensional and four-dimensional spin foam models this amounts to modifying the vertex amplitude such that the exponential asymptotics is obtained. In particular, we show that the ELPR/FK model vertex amplitude can be modified such that the new model is finite and has the Einstein-Hilbert action as its classical limit. We also calculate the first-order and some of the second-order quantum corrections in the semi-classical expansion of the effective action.

  12. Assessing the Effectiveness of an Evidence-based Practice Pharmacology Course Using the Fresno Test.

    Science.gov (United States)

    Gardner, Alice; Lahoz, Monina R; Bond, Irena; Levin, Len

    2016-09-25

    Objective. To assess the effectiveness of an evidence-based practice (EBP) pharmacology elective course to teach EBP skills using the Fresno Test (FT). Methods. Pharmacy faculty members and medical librarians developed the elective course and offered it to two cohorts of doctor of pharmacy (PharmD) students. A pre/post intervention study design was used. Seven of 12 FT items were chosen to measure specific EBP skills: Ask, Access, Appraise and Apply. Pre/postcomposite and FT item mean scores were compared using Student's t test with p<0.05 set as significant a priori. Results. Composite FT mean scores increased significantly for both cohorts. Mean scores for both cohorts increased significantly in four of the seven FT items but on different FT items. Conclusion. As a profession that commonly uses evidence-based guidelines, developing and integrating an EBP course in the PharmD curriculum is worth considering.

  13. Action-effect learning in early childhood: does language matter?

    Science.gov (United States)

    Karbach, Julia; Kray, Jutta; Hommel, Bernhard

    2011-07-01

    Previous work showed that language has an important function for the development of action control. This study examined the role of verbal processes for action-effect learning in 4-year-old children. Participants performed an acquisition phase including a two-choice key-pressing task in which each key press (action) was followed by a particular sound (effect). Children were instructed to either (1) label their actions along with the corresponding effects, (2) verbalize task-irrelevant words, (3) or perform without verbalization. In a subsequent test phase, they responded to the same sound effects either under consistent or under inconsistent sound-key mappings. Evidence for action-effect learning was obtained only if action and effects were labeled or if no verbalization was performed, but not if children verbalized task-irrelevant labels. Importantly, action-effect learning was most pronounced when children verbalized the actions and the corresponding effects, suggesting that task-relevant verbal labeling supports the integration of event representations.

  14. Singularity-free cosmological solutions of the superstring effective action

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, I. (Ecole Polytechnique, 91 - Palaiseau (France). Centre de Physique Theorique); Rizos, J. (Ecole Polytechnique, 91 - Palaiseau (France). Centre de Physique Theorique); Tamvakis, K. (Ioannina Univ. (Greece). Dept. of Physics)

    1994-03-07

    We study the cosmological solutions of the one-loop corrected superstring effective action, in a Friedmann-Robertson-Walker background, and in the presence of the dilaton and modulus fields. A particularly interesting class of solutions is found which avoid the initial singularity and are consistent with the perturbative treatment of the effective action. (orig.)

  15. Kaluza-Klein monopole and 5-brane effective actions

    NARCIS (Netherlands)

    Eyras, E; Lozano, Y

    2000-01-01

    We review the construction of the Kaluza-Klein monopole of the Type IIA theory in the most general case of a massive background, as well as its relation via T-duality with the Type IIB NS-5-brane. This last effective action is shown to be related by S-duality to the D5-brane effective action. [GRAPH

  16. Gauge dependence of the effective action in Einstein gravity

    Energy Technology Data Exchange (ETDEWEB)

    Lavrov, P.M.; Reshetnyak, A.A. [Tomsk State Pedagogical Institute (Russian Federation)

    1995-10-01

    Einstein gravity is considered in a special one-parameter background gauge. The one-loop effective action of the theory is calculated to the first order in the gauge parameter. It is shown that, on the mass shell, the effective action is independent of the gauge parameter. 57 refs.

  17. Pharmacological and clinical properties of curcumin

    Directory of Open Access Journals (Sweden)

    Huang S

    2011-06-01

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

  18. Phosphodiesterase inhibitors: history of pharmacology.

    Science.gov (United States)

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

    2011-01-01

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

  19. RECENT DEVELOPMENT OF SYNTHESIS,MECHANISM OF PHARMACOLOGICAL ACTIONS AND METAL COMPLEXES OF SULFASALAZINE%柳氮磺胺吡啶的合成、药理及配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康澍; 陈振锋; 梁宏

    2002-01-01

    柳氮磺胺吡啶具有消炎和抗菌的性质,主要用于治疗溃疡性结肠炎和类风湿关节炎.对柳氮磺胺吡啶的合成、药理和金属配合物研究进展进行了评述.%Sulfasalazine possesses both anti-inflammatory and antibacterial properties and was mainly used to treat inflammatory bowel disease and rheumatoid arthritis. This paper summarizes recent development of synthesis,pharmacological actions,mechanisms of actions and metal complexes of sulfasalazine.

  20. Pharmacological effects of ethanol extract of Egyptian Artemisia herba-alba in rats and mice

    Institute of Scientific and Technical Information of China (English)

    Heba Mohammed Ibrahim Abdallah; Nawal E.L. Sayed Gomaa

    2016-01-01

    Objective: To investigate some pharmacological effects including gastroprotective, anti-inflammatory, analgesic, antipyretic and in vitro antioxidant effects of Artemisia herba-alba extract in different experimental models. Methods: Inflammation was induced in rat paw by subcutaneous injection of 1% (v/v) carrageenan solution. Writhes was induced in mice by intraperitoneal injection of 0.6%(v/v) acetic acid solution. Pyrexia was induced using Brewer's yeast suspension. Gastric lesion was induced in rats by oral administration of 99% ethanol. The anti-inflammatory, analgesic, antipyretic and gastroprotective activities of Artemisia herba-alba extract were investigated respectively. In vitro antioxidant effect was investigated using DPPH free radical. Results: The plant extract showed anti-inflammatory effect in carrageenan-induced paw edema in rats, analgesic effect against acetic acid-induced writhing, and antipyretic ac-tivity in Brewer's yeast model of pyrexia. Besides, it was shown to be a gastroprotective agent against ethanol-induced gastric ulcers. The plant also exhibited a free radical scavenging potential in an in vitro antioxidant study using DPPH. Conclusions: The results validate the use of the investigated plant in traditional medicine for different ailments.

  1. Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists

    Energy Technology Data Exchange (ETDEWEB)

    Menon, M.K.; Dinovo, E.C.; Haddox, V.G.

    1987-09-28

    The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. 19 references, 8 figures, 2 tables.

  2. Advances in Experimental Pharmacological Studies of Effects of Astragalus on Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    han; ling

    2001-01-01

    Astragalus (AS), a traditional Chinese tonic medicine, refers to the dry root of perenial herbaceous plants Astragalus membranaceus (Fisch) and Astragalus mongolicus Bge of leguminosae family, which was first recorded in "Shen Nong's Herbal Classic" (神农本草经). The herb is sweet in flavor, slightly warm in nature and acts on the Spleen and Lung channels. It was described that AS possesses the effects of "invigorating Qi to elevate Yang,consolidating superficies to stop sweating, inducing diuresis to remove edema and promoting healing of sore to regenerate tissue". Its chemical components have been discovered to be AS-saponins (ASS), AS-general flavone (AGF), AS-polysaccharides (APS), amino acid and microelements. During the past two decades, the effects of AS, the prescriptions containing AS and its active components on cardiovascular system have been widely studied(1,2). Its effects of positive inotropic action,reducing blood pressure, and in protecting myocardia against injuries caused by ischemia and ischemia/reperfusion or virus infection have been well documented. The underlying mechanisms of the effects have also been deeply studied. This paper summarizes the pharmacological studies on the effects of AS on cardiovascular system conducted in recent years.……

  3. Advances in Experimental Pharmacological Studies of Effects of Astragalus on Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    韩玲; 陈可冀

    2001-01-01

    @@Astragalus (AS), a traditional Chinese tonic medicine, refers to the dry root of perenial herbaceous plants Astragalus membranaceus (Fisch) and Astragalus mongolicus Bge of leguminosae family, which was first recorded in "Shen Nong's Herbal Classic" (神农本草经). The herb is sweet in flavor, slightly warm in nature and acts on the Spleen and Lung channels. It was described that AS possesses the effects of "invigorating Qi to elevate Yang,consolidating superficies to stop sweating, inducing diuresis to remove edema and promoting healing of sore to regenerate tissue". Its chemical components have been discovered to be AS-saponins (ASS), AS-general flavone (AGF), AS-polysaccharides (APS), amino acid and microelements. During the past two decades, the effects of AS, the prescriptions containing AS and its active components on cardiovascular system have been widely studied(1,2). Its effects of positive inotropic action,reducing blood pressure, and in protecting myocardia against injuries caused by ischemia and ischemia/reperfusion or virus infection have been well documented. The underlying mechanisms of the effects have also been deeply studied. This paper summarizes the pharmacological studies on the effects of AS on cardiovascular system conducted in recent years.

  4. High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides

    Science.gov (United States)

    Yang, B.; Ming, X.; Cao, C.; Laing, B.; Yuan, A.; Porter, M. A.; Hull-Ryde, E. A.; Maddry, J.; Suto, M.; Janzen, W. P.; Juliano, R. L.

    2015-01-01

    The therapeutic use of antisense and siRNA oligonucleotides has been constrained by the limited ability of these membrane-impermeable molecules to reach their intracellular sites of action. We sought to address this problem using small organic molecules to enhance the effects of oligonucleotides by modulating their intracellular trafficking and release from endosomes. A high-throughput screen of multiple small molecule libraries yielded several hits that markedly potentiated the actions of splice switching oligonucleotides in cell culture. These compounds also enhanced the effects of antisense and siRNA oligonucleotides. The hit compounds preferentially caused release of fluorescent oligonucleotides from late endosomes rather than other intracellular compartments. Studies in a transgenic mouse model indicated that these compounds could enhance the in vivo effects of a splice-switching oligonucleotide without causing significant toxicity. These observations suggest that selected small molecule enhancers may eventually be of value in oligonucleotide-based therapeutics. PMID:25662226

  5. Effectiveness of Non-Pharmacological Interventions to Prevent Falls in Older People: A Systematic Overview. The SENATOR Project ONTOP Series

    Science.gov (United States)

    Rimland, Joseph M.; Abraha, Iosief; Dell’Aquila, Giuseppina; Cruz-Jentoft, Alfonso; Soiza, Roy; Gudmusson, Adalsteinn; Petrovic, Mirko; O’Mahony, Denis; Todd, Chris; Cherubini, Antonio

    2016-01-01

    Background Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. Objectives To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. Methods We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. Results Fifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. Conclusions The aim of this overview of

  6. Genetic or pharmacological blockade of noradrenaline synthesis enhances the neurochemical, behavioural, and neurotoxic effects of methamphetamine

    Science.gov (United States)

    Weinshenker, David; Ferrucci, Michela; Busceti, Carla L.; Biagioni, Francesca; Lazzeri, Gloria; Liles, L. Cameron; Lenzi, Paola; Murri, Luigi; Paparelli, Antonio; Fornai, Francesco

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus coeruleus (LC), the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH). However, because noradrenergic terminals contain other neuromodulators and the noradrenaline (NA) transporter, which may act as a neuroprotective buffer, it was unclear whether this enhancement of METH neurotoxicity was caused by the loss of noradrenergic innervation or the loss of NA itself. We addressed the specific role of NA by comparing the effects of METH in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic terminals but specifically lacking NA (genetic or acute pharmacological blockade of the NA biosynthetic enzyme dopamine β-hydroxylase; DBH). We found that genetic deletion of DBH (DBH −/− mice) and acute treatment of wild-type mice with a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH responses. All three methods of NA depletion enhanced striatal DA release, extracellular oxidative stress (as measured by in vivo microdialysis of DA and 2,3-dihydroxybenzoic acid), and behavioural stereotypies following repeated METH administration. These effects accompanied a worsening of the striatal DA neuron terminal damage and ultrastructural changes to medium spiny neurons. We conclude that NA itself is neuroprotective and plays a fundamental role in the sensitivity of striatal DA terminals to the neurochemical, behavioural, and neurotoxic effects of METH. PMID:18042179

  7. Neuroimaging studies towards understanding the central effects of pharmacological cannabis products on patients with epilepsy.

    Science.gov (United States)

    Allendorfer, Jane B; Szaflarski, Jerzy P

    2017-05-01

    Recent interest for the use of cannabis-derived products as therapeutic agents in the treatment of epilepsies has necessitated a reevaluation of their effects on brain and behavior. Overall, prolonged cannabis use is thought to result in functional and structural brain alterations. These effects may be dependent on a number of factors: e.g., which phytocannabinoid is used (e.g., cannabidiol (CBD) vs. tetrahyrocannabinol (THC)), the frequency of use (occasional vs. heavy), and at what age (prenatal, childhood, adulthood) the use began. However, due to the fact that there are over seven hundred constituents that make up the Cannabis sativa plant, it is difficult to determine which compound or combination of compounds is responsible for specific effects when studying recreational users. Therefore, this review focuses only on the functional MRI studies investigating the effects of specific pharmacological preparations of cannabis compounds, specifically THC, tetrahydrocannabivarin (THCV), and CBD, on brain function in healthy individuals and persons with epilepsy with references to non-epilepsy studies only to underline the gaps in research that need to be filled before cannabis-derived products are considered for a wide use in the treatment of epilepsy. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

  8. [Pharmacologic and enzymatic effects of snake venoms from Antioquia and Choco (Colombia)].

    Science.gov (United States)

    Otero, R; Guillermo Osorio, R; Valderrama, R; Augusto Giraldo, C

    1992-01-01

    We compared several pharmacological and enzymatic effects induced by 11 snake venoms from seven species, six of them from different geographic areas of Antioquia and Choco, north-west of Colombia, South America (Bothrops atrox, B. nasutus, B. schlegelii, B. punctatus, Lachesis muta, Micrurus mipartitus), and Crotalus durissus terrificus venom, from specimens captured in other provinces of the country (Tolima, Huila, Meta and Atlantico). Differences were observed in edema-forming, hemorrhage, defibrination, indirect hemolysis, myonecrosis, proteolysis and lethal activity between venoms from different genera or species, as well as according to the geographic area of origin in B. atrox and B. nasutus snake venoms. Bothrops venoms, in particular B. atrox and L. muta, produced major local effects. All of the venoms, including M. mipartitus, had myotoxic effects. The most defibrinating venoms were B. atrox, L. muta, B. punctatus and C. d. terrificus. All of the venoms had indirect hemolytic activity; the venom of M. mipartitus being greatest. The most lethal venoms were those of C. d. terrificus and M. mipartitus. Within Bothrops species, the venom of B. schlegelii was the least active in terms of local and systemic pathologic effects.

  9. Adverse effects of pharmacological therapy for nicotine addiction in smokers following a smoking cessation program.

    Science.gov (United States)

    Barrueco, Miguel; Otero, María José; Palomo, Luis; Jiménez-Ruiz, Carlos; Torrecilla, Miguel; Romero, Pedro; Riesco, Juan Antonio

    2005-06-01

    This multicenter, community-based, prospective, longitudinal study evaluated the safety of nicotine replacement therapy (NRT), bupropion, and combined therapy of NRT and bupropion for smokers seeking to quit, when these therapies were used under real-world conditions following a smoking cessation program. Participants were smokers aged 18 years or older who attended five smoking cessation clinics. Evaluations were made at 15, 30, 60, and 90 days. We investigated the possible existence of adverse effects as well as the severity of each adverse effect and its influence on the treatment course. The study included 904 smokers: 370 received NRT, 413 received bupropion, and 121 received combined therapy. At 15, 30, 60, and 90 days, adverse effects were reported by 43.8%, 33.1%, 22.3%, and 5.7% of subjects, respectively. Adverse effects were significantly more frequent in subjects receiving combined therapy or bupropion alone than in NRT-treated subjects at the 15-, 30-, and 60-day follow-ups. A total of 83 smokers (9.3%) withdrew from treatment and 116 (12.8%) stopped temporarily because of adverse effects. No differences were found in the percentages of discontinuation among the different treatment options. Adverse effects rarely were severe (n=10). Nevertheless, 41 subjects (4.5%) discontinued drug therapy indefinitely and 55 (6.1%) discontinued it temporarily because of mild adverse effects. Pharmacological therapies for smoking cessation are safe as long as they are appropriately prescribed and supervised by clinicians according to clinical practice guidelines. Adverse effects are primarily mild. Nonetheless, mild adverse effects may be perceived by patients as a serious enough problem to cause them to discontinue treatment.

  10. The pharmacology of salmeterol.

    Science.gov (United States)

    Johnson, M

    1990-01-01

    The pharmacology of salmeterol hydroxynaphthoate (SALM) has been investigated in respiratory tissues in vitro and in animal models in vivo. In guinea pig trachea and human bronchial smooth muscle, SALM was more potent than isoprenaline (ISO), salbutamol (SALB), and clenbuterol (CLEN). The duration of action was greater than 7 h, whereas that for ISO, SALB, and CLEN was 2, 11, and 45 min, respectively. The sustained activity of SALM was reversed by sotalol, but was reestablished when the beta-blocker was removed. SALM was greater than 3000-fold weaker than ISO in cardiac tissues, indicating high beta 2-adrenoceptor selectivity. In the conscious guinea pig, aerosolized SALM, SALB, and CLEN caused dose-related bronchodilatation. The activity of SALM persisted for at least 6 h, compared with less than 2 h for SALB and CLEN. SALM is also a potent inhibitor of mediator release from human lung, this effect being sustained for up to 20 hours. In guinea pig airways in vivo, SALM inhibited histamine-induced plasma protein extravasation for approximately 8 h. Salmeterol is a potent and selective beta 2-adrenoceptor agonist with a unique profile of action. It induces persistent bronchodilatation, sustained suppression of mediator release, and long-lasting inhibition of edema formation. This combination of properties may represent an important new advance in the treatment of bronchial asthma.

  11. Duality symmetries and the type II string effective action

    NARCIS (Netherlands)

    Bergshoeff, E.

    1996-01-01

    We discuss the duality symmetries of Type II string effective actions in nine, ten and eleven dimensions. As a by-product we give a covariant action underlying the ten-dimensional Type IIB supergravity theory. We apply duality symmetries to construct dyonic Type II string solutions in six dimensions

  12. Effective action for EPRL/FK spin foam models

    CERN Document Server

    Mikovic, Aleksandar

    2011-01-01

    We show that a natural modification of the EPRL/FK vertex amplitude gives a finite spin foam model whose effective action gives the Einstein-Hilbert action in the limit of large spins and arbitrarily fine spacetime triangulations. The first-order quantum corrections can be easily computed and we show how to calculate the higher-order corrections.

  13. Effective action for hard thermal loops in gravitational fields

    Directory of Open Access Journals (Sweden)

    R.R. Francisco

    2016-05-01

    Full Text Available We examine, through a Boltzmann equation approach, the generating action of hard thermal loops in the background of gravitational fields. Using the gauge and Weyl invariance of the theory at high temperature, we derive an explicit closed-form expression for the effective action.

  14. System biology analysis of long-term effect and mechanism of Bufei Yishen on COPD revealed by system pharmacology and 3-omics profiling

    Science.gov (United States)

    Li, Jiansheng; Zhao, Peng; Yang, Liping; Li, Ya; Tian, Yange; Li, Suyun

    2016-01-01

    System pharmacology identified 195 potential targets of Bufei Yishen formula (BYF), and BYF was proven to have a short-term therapeutic effect on chronic obstructive pulmonary disease (COPD) rats previously. However, the long-term effect and mechanism of BYF on COPD is still unclear. Herein, we explored its long-term effect and underlying mechanism at system level. We administered BYF to COPD rats from week 9 to 20, and found that BYF could prevent COPD by inhibiting the inflammatory cytokines expression, protease-antiprotease imbalance and collagen deposition on week 32. Then, using transcriptomics, proteomics and metabolomics analysis, we identified significant regulated genes, proteins and metabolites in lung tissues of COPD and BYF-treated rats, which could be mainly attributed to oxidoreductase-antioxidant activity, focal adhesion, tight junction or lipid metabolism. Finally, based on the comprehensive analysis of system pharmacology target, transcript, protein and metabolite data sets, we found a number of genes, proteins, metabolites regulated in BYF-treated rats and the target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhension. In conclusion, BYF exerts long-term therapeutic action on COPD probably through modulating the lipid metabolism, oxidative stress, cell junction and inflammatory response pathways at system level. PMID:27146975

  15. Effect of metal complexation to anti-inflammatory over the action against oxidative and free radicals: ketoprofen action; Efeito da complexacao de metais aos antiinflamatorios na acao contra agentes oxidativos e radicais livres: acao do cetoprofeno

    Energy Technology Data Exchange (ETDEWEB)

    Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio [UEPG, Universidade Estadual de Ponta Grossa, Departamento de Analises Clinicas eToxicologicas, Ponta Grossa, PR (Brazil); Khalil, Omar Arafat Kdudsi [IFG, Instituto Federal de Goias, Campus de Formosa, Formosa - GO (Brazil); Carvalho, Claudio Teodoro de [UFGD, Universidade Federal da Grande Dourados, Faculdade de Ciencias Exatas e Tecnologias, Dourados-MS (Brazil); Bannach, Gilbert [UNESP, Universidade Estadual Paulista Julio de Mesquita Filho, Faculdade de Ciencias de Bauru, Bauru, SP (Brazil)

    2011-07-01

    Free radicals are highly reactive species generated in living organisms for the purpose of protection. However, in some circumstances, they are responsible for the occurrence or aggravation of tissue damage. Many anti-inflammatory drugs have a direct effect on free radicals and not radical reactive species, which contributes to its actions against inflammation. Ketoprofen is a nonsteroidal anti-inflammatory agent that generates free radicals by photo irradiation and has an important hemolytic effect with that. The complexation of metals to different drugs has been used as a strategy to improve the pharmacological action of different molecules and reduce their side effects. This paper presents the results of ketoprofen and their metallic complexes action on erythrocytes and free radicals. It was observed that the cerium enhances the scavenger properties of ketoprofen on free radicals, while copper enhances its action over non-radical oxidants. Copper also reduced the hemolytic effect presented by ketoprofen meanwhile its cerium derivative maintained it. (author)

  16. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects.

    Science.gov (United States)

    Prozialeck, Walter C; Jivan, Jateen K; Andurkar, Shridhar V

    2012-12-01

    Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.

  17. Effects of a novel pharmacologic inhibitor of myeloperoxidase in a mouse atherosclerosis model.

    Science.gov (United States)

    Liu, Cuiqing; Desikan, Rajagopal; Ying, Zhekang; Gushchina, Liubov; Kampfrath, Thomas; Deiuliis, Jeffrey; Wang, Aixia; Xu, Xiaohua; Zhong, Jixin; Rao, Xiaoquan; Sun, Qinghua; Maiseyeu, Andrei; Parthasarathy, Sampath; Rajagopalan, Sanjay

    2012-01-01

    Inflammation and oxidative stress play fundamental roles in the pathogenesis of atherosclerosis. Myeloperoxidase has been extensively implicated as a key mediator of inflammatory and redox-dependent processes in atherosclerosis. However, the effect of synthetic myeloperoxidase inhibitors on atherosclerosis has been insufficiently studied. In this study, ApoE(-/-) mice were randomized to low- and high-dose INV-315 groups for 16 weeks on high-fat diet. INV-315 resulted in reduced plaque burden and improved endothelial function in response to acetylcholine. These effects occurred without adverse events or changes in body weight or blood pressure. INV-315 treatment resulted in a decrease in iNOS gene expression, superoxide production and nitrotyrosine content in the aorta. Circulating IL-6 and inflammatory CD11b(+)/Ly6G(low)/7/4(hi) monocytes were significantly decreased in response to INV-315 treatment. Acute pretreatment with INV-315 blocked TNFα-mediated leukocyte adhesion in cremasteric venules and inhibited myeloperoxidase activity. Cholesterol efflux was significantly increased by high-dose INV-315 via ex-vivo reverse cholesterol transport assays. Our results suggest that myeloperoxidase inhibition may exert anti-atherosclerotic effects via inhibition of oxidative stress and enhancement of cholesterol efflux. These findings demonstrate a role for pharmacologic modulation of myeloperoxidase in atherosclerosis.

  18. Effectiveness and student perspective of a pilot effort in team based learning in pharmacology for medical undergraduate

    Directory of Open Access Journals (Sweden)

    Nayana K. Hashilkar

    2016-08-01

    Conclusions: Team-Based Learning is an effective teaching-learning method to teach pharmacology to medical undergraduates. It encourages pre-class preparation, student's participation in small teams and improves their basic knowledge as well as skills of critical thinking. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1413-1416

  19. 粉防己碱在炎症性肺部疾病中的药理作用%Pharmacological actions of tetrandrine in inflammatory pulmonary diseases

    Institute of Scientific and Technical Information of China (English)

    谢强敏; 汤慧芳; 陈季强; 卞如濂

    2002-01-01

    Tetrandrine is a principle from a traditional Chinese medicine of the root of Stephania tetrandra S Moore approved by State Drugs Adminstration of China as a new drug for the treatment of silicosis. Except for its antiinflammatory, antifibrogenetic, immunomodulating effects and antioxidant effects, tetrandrine presents antiallergic effects, inhibitory effects on pulmonary vessels and airway smooth muscle contraction, and platelet aggregation via its nonspecific calcium channel antagonism that suggested its potential in the treatment of asthma,pulmonary hypertension and chronic obstructive pulmonary disease (COPD). In general, the clinical results to date with tetrandrine in asthma and pulmonary hypertension have been exciting. The last 10 years have witnessed great leaps forward in our understanding of the molecular biology and biochemistry of chronic inflammatory diseases as well as the treatment drugs, which may create opportunities for future therapeutic innovation, development of tetrandrine derivatives or new extracts from other Chinese medicine. The current article briefly reviews the basic and clinical pharmacology of tetrandrine as well as the in vitro and in vivo data supporting the view that tetrandrine is as a novel drug for the treatment of silicosis, asthma and pulmonary hypertension.%粉防己碱具有抗炎、抗变态反应、抗氧化、抗纤维化、抗血小板聚集和免疫调节等多方面的药理作用,已用于治疗矽肺,对哮喘和COPD继发的肺动脉高压也有明显的改善作用.

  20. Effective Action of Scalar QED in Electric Field Backgrounds

    CERN Document Server

    Kim, Sang Pyo; Yoon, Yongsung

    2008-01-01

    We use the evolution operator method to find the one-loop effective action of scalar QED in electric field backgrounds in terms of the Bogoliubov coefficient between the ingoing and the outgoing vacuum. The effective action shows the general relation between the vacuum persistence and the mean number of created pairs for any electric field. We obtain the exact effective action for a constant electric field and a pulsed electric field, E_0 sech^2 (t/tau), and show that the imaginary part correctly yields the vacuum persistence.

  1. Techniques for calculations with nPI effective actions

    Directory of Open Access Journals (Sweden)

    Carrington M.E.

    2015-01-01

    Full Text Available We consider a symmetric scalar theory with quartic coupling in 2- and 3- dimensions and compare the self-consistent 4-point vertex obtained from the 4PI effective action with the Bethe-Salpeter 4-vertex from 2PI effective action. We show that when the coupling is large the contributions from the higher order effective action are large. We also show that one can solve the 2PI equations of motion in 4-dimensions, without introducing counter-terms, using a renormalization group method. This method provides a promising starting point to study the renormalization of higher order nPI theories.

  2. Effective supergravity actions for flop transitions

    Energy Technology Data Exchange (ETDEWEB)

    Jarv, Laur; Mohaupt, Thomas; Saueressig, Frank E-mail: F.Saueressig@tpi.uni-jena.de

    2003-12-01

    We construct a family of five-dimensional gauged supergravity actions which describe flop transitions of M-theory compactified on Calabi-Yau three folds. While the vector multiplet sector can be treated exactly, we use the Wolf spaces X(1+N) = U(1+N,2)/(U(1+N) x U(2)) to model the universal hyper multiplet together with N charged hyper multiplets corresponding to winding states of the M2-brane. The metric, the Killing vectors and the moment maps of these spaces are obtained explicitly by using the superconformal quotient construction of quaternion-Kaehler manifolds. The inclusion of the extra hyper multiplets gives rise to a non-trivial scalar potential which is uniquely fixed by M-theory physics. (author)

  3. On the influence of reward on action-effect binding

    Directory of Open Access Journals (Sweden)

    Paul Simon Muhle-Karbe

    2012-11-01

    Full Text Available Ideomotor theory states that the formation of anticipatory representations about the perceptual consequences of an action (i.e. action-effect (A-E binding provides the functional basis of voluntary action control. A host of studies has demonstrated that A-E binding occurs fast and effortlessly, yet only little is known about cognitive and affective factors that influence this learning process. In the present study, we sought to test whether the motivational value of an action modulates the acquisition of A-E associations. To this end, we associated specific actions with monetary incentives during the acquisition of novel A-E mappings. In a subsequent test phase, the degree of binding was assessed by presenting the former effect stimuli as task-irrelevant response primes in a forced-choice response task in the absence of any reward. Binding, as indexed by response priming through the former action effects, was only found for reward-related A-E mappings. Moreover, the degree to which reward associations modulated the binding strength was predicted by individuals’ trait sensitivity to reward. These observations indicate that the association of actions and their immediate outcomes depends on the motivational value of the action during learning, as well as on the motivational disposition of the individual. On a larger scale, these findings also highlight the link between ideomotor theories and reinforcement-learning theories, providing an interesting perspective for future research on anticipatory regulation of behavior.

  4. 植物雌激素类化合物的药理作用及机制研究%Study on pharmacological actions and mechanisms of phytoestrogen compounds

    Institute of Scientific and Technical Information of China (English)

    邢冷; 宋辉; 高佳雪; 陈晨; 李文兰

    2016-01-01

    At present epidemiological studies found that phytoestrogen plays an important role in the prevention and the occurrence of cancer , and inhibit the growth and proliferation of tumor cells, including mammary cancer, prostate cancer, endometrial carcinoma, ovarian cancer , colon carcinoma , leukemia , and hepatic carcinoma and gastric cancer .In vivo es-trogen secretion disorder or estrogen receptor metabolism disorders often can induce a variety of related diseases or accelerate the process of disease , long-term intake of phytoestrogens may have on endometrial , breast , and negative effects on the male reproductive system .The pharmacological effects of phytoestrogens will still need to examine , on the adverse reaction mechanisms need to be further explored .This paper described the pharmacological effects and mechanism of action of phytoestrogen studies .%目前流行病学研究发现,植物雌激素在疾病的预防和治疗方面发挥重要作用,对心血管疾病、围绝经期综合症、乳腺癌、子宫内膜癌、结肠癌等肿瘤具有预防和抑制作用。体内雌激素分泌紊乱或雌激素受体代谢失常可诱发多种相关疾病或加速疾病进程,长期摄入植物雌激素可能对子宫内膜、乳腺以及男性生殖系统产生不良影响。所以植物雌激素的药理学作用仍需要进行研究,对其不良反应作用机制等需要进一步探讨。介绍了有关植物雌激素的药理学作用及其作用机制的研究。

  5. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer

    National Research Council Canada - National Science Library

    Kwang-tae CHOI

    2008-01-01

    Korean Panax ginseng C A Meyer is mainly used to maintain the homeostasis of the body, and the pharmacological efficacy of Korean ginseng identified by modem science includes improved brain function...

  6. Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.

    Science.gov (United States)

    Angotti, C; Venier-Julienne, M C; Penna, C; Femminò, S; Sindji, L; Paniagua, C; Montero-Menei, C N; Pagliaro, P

    2016-11-22

    Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.

  7. Small group effectiveness during pharmacology learning sessions in a Nepalese medical school

    Directory of Open Access Journals (Sweden)

    Shankar PR

    2011-06-01

    Full Text Available BackgroundSmall group learning sessions are used in pharmacology atthe KIST Medical College, Lalitpur, Nepal. Feedback aboutstudent behaviours that enhance and hinder small groupeffectiveness was obtained. This will help us improve thesmall group sessions and will also be useful to educatorsusing small groups in other medical schools.MethodThe small groups were self-managing with a group leader,time-keeper, recorder and presenter. Small groupeffectiveness was measured using the Tutorial GroupEffectiveness Instrument (TGEI developed by Singaram andco-authors. The instrument was administered in June 2010and key findings obtained were shared with students andfacilitators. The instrument was administered again inAugust. The mean cognitive, motivational, demotivationaland overall scores were compared among differentcategories of respondents in June and August. Scores werealso compared between June and August 2010.ResultsA total of 89 students participated in the study in June and88 in August 2010. In June, females rated overall groupproductivity higher compared to males. The cognitive andmotivational scores were higher in August 2010 while thedemotivational score was lower.ConclusionThe small group effectiveness was higher in August after theeducational intervention which utilised feedback aboutproblems observed, theoretical considerations of effectivesmall groups and how this information can be applied inpractice.

  8. Tics and other stereotyped movements as side effects of pharmacological treatment.

    Science.gov (United States)

    Madruga-Garrido, Marcos; Mir, Pablo

    2013-01-01

    Tics and other stereotyped abnormal movements can be seen as adverse effects of some pharmacologic drugs. Among these drugs, antipsychotics may provoke tardive syndromes after a chronic exposure, primarily in the case of typical antipsychotics. These syndromes include tardive tics, tardive dyskinesia, or tardive akathisia, which present with tics or stereotyped movements as a clinical phenomenon. Psychostimulants (mainly methylphenidate) have traditionally been associated with the appearance of tics due to the increased dopamine activity caused by stimulants. Nevertheless, in recent years, several studies have concluded not only that methylphenidate does not exacerbate or reactivate tics but also that tics can improve with its use in patients with associated attention deficit and hyperactivity disorder and tic disorder. Antiepileptic drugs, although infrequently, can also induce tics, with carbamazepine and lamotrigine described as tic inducers. Other antiepileptics, including levetiracetam and topiramate, have been proposed as a potential treatment for tic disorders due to a positive effect on tics, especially in those with associated epileptic disorder. Clinical and therapeutic approaches to tics and stereotyped movements after exposure to antipsychotics, stimulants, and antiepileptic drugs will be reviewed in this chapter.

  9. The internal anticipation of sensory action effects: when action induces FFA and PPA activity

    Directory of Open Access Journals (Sweden)

    Simone Kühn

    2010-06-01

    Full Text Available Voluntary action – in particular the ability to produce desired effects in the environment – is fundamental to human existence. According to ideomotor theory we can achieve goals in the environment by means of anticipating their outcomes. We aimed at providing neurophysiological evidence for the assumption that performing actions calls for the activation of brain areas associated with the sensory effects usually evoked by the actions. We conducted an fMRI study in which right and left button presses lead to the presentation of face and house pictures. We compared a baseline phase with the same phase after participants experienced the association between button presses and pictures. We found an increase in the parahippocampal place area (PPA for the response that has been associated with house pictures and fusiform face area (FFA for the response that has been coupled with face pictures. This observation constitutes support for ideomotor theory.

  10. Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga

    Directory of Open Access Journals (Sweden)

    Nagano Celso S

    2008-06-01

    Full Text Available Abstract Background An interaction between lectins from marine algae and PLA2 from rattlesnake was suggested some years ago. We, herein, studied the effects elicited by a small isolectin (BTL-2, isolated from Bryothamnion triquetrum, on the pharmacological and biological activities of a PLA2 isolated from rattlesnake venom (Crotalus durissus cascavella, to better understand the enzymatic and pharmacological mechanisms of the PLA2 and its complex. Results This PLA2 consisted of 122 amino acids (approximate molecular mass of 14 kDa, its pI was estimated to be 8.3, and its amino acid sequence shared a high degree of similarity with that of other neurotoxic and enzymatically-active PLA2s. BTL-2 had a molecular mass estimated in approximately 9 kDa and was characterized as a basic protein. In addition, BTL-2 did not exhibit any enzymatic activity. The PLA2 and BTL-2 formed a stable heterodimer with a molecular mass of approximately 24–26 kDa, estimated by molecular exclusion HPLC. In the presence of BTL-2, we observed a significant increase in PLA2 activity, 23% higher than that of PLA2 alone. BTL-2 demonstrated an inhibition of 98% in the growth of the Gram-positive bacterial strain, Clavibacter michiganensis michiganensis (Cmm, but only 9.8% inhibition of the Gram-negative bacterial strain, Xanthomonas axonopodis pv passiflorae (Xap. PLA2 decreased bacterial growth by 27.3% and 98.5% for Xap and Cmm, respectively, while incubating these two proteins with PLA2-BTL-2 inhibited their growths by 36.2% for Xap and 98.5% for Cmm. PLA2 significantly induced platelet aggregation in washed platelets, whereas BTL-2 did not induce significant platelet aggregation in any assay. However, BTL-2 significantly inhibited platelet aggregation induced by PLA2. In addition, PLA2 exhibited strong oedematogenic activity, which was decreased in the presence of BTL-2. BTL-2 alone did not induce oedema and did not decrease or abolish the oedema induced by the 48

  11. Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga

    Science.gov (United States)

    Oliveira, Simone CB; Fonseca, Fabiana V; Antunes, Edson; Camargo, Enilton A; Morganti, Rafael P; Aparício, Ricardo; Toyama, Daniela O; Beriam, Luís OS; Nunes, Eudismar V; Cavada, Benildo S; Nagano, Celso S; Sampaio, Alexandre H; Nascimento, Kyria S; Toyama, Marcos H

    2008-01-01

    Background An interaction between lectins from marine algae and PLA2 from rattlesnake was suggested some years ago. We, herein, studied the effects elicited by a small isolectin (BTL-2), isolated from Bryothamnion triquetrum, on the pharmacological and biological activities of a PLA2 isolated from rattlesnake venom (Crotalus durissus cascavella), to better understand the enzymatic and pharmacological mechanisms of the PLA2 and its complex. Results This PLA2 consisted of 122 amino acids (approximate molecular mass of 14 kDa), its pI was estimated to be 8.3, and its amino acid sequence shared a high degree of similarity with that of other neurotoxic and enzymatically-active PLA2s. BTL-2 had a molecular mass estimated in approximately 9 kDa and was characterized as a basic protein. In addition, BTL-2 did not exhibit any enzymatic activity. The PLA2 and BTL-2 formed a stable heterodimer with a molecular mass of approximately 24–26 kDa, estimated by molecular exclusion HPLC. In the presence of BTL-2, we observed a significant increase in PLA2 activity, 23% higher than that of PLA2 alone. BTL-2 demonstrated an inhibition of 98% in the growth of the Gram-positive bacterial strain, Clavibacter michiganensis michiganensis (Cmm), but only 9.8% inhibition of the Gram-negative bacterial strain, Xanthomonas axonopodis pv passiflorae (Xap). PLA2 decreased bacterial growth by 27.3% and 98.5% for Xap and Cmm, respectively, while incubating these two proteins with PLA2-BTL-2 inhibited their growths by 36.2% for Xap and 98.5% for Cmm. PLA2 significantly induced platelet aggregation in washed platelets, whereas BTL-2 did not induce significant platelet aggregation in any assay. However, BTL-2 significantly inhibited platelet aggregation induced by PLA2. In addition, PLA2 exhibited strong oedematogenic activity, which was decreased in the presence of BTL-2. BTL-2 alone did not induce oedema and did not decrease or abolish the oedema induced by the 48/80 compound. Conclusion The

  12. 辣椒碱药理作用的分子机制研究进展%Recent advances in molecular mechanisms of capsaicin′s pharmacological effect

    Institute of Scientific and Technical Information of China (English)

    王荣雁; 陈朝军; 武世奎; 高丽娜; 周南

    2016-01-01

    目的:对近年来辣椒碱的药理活性及其分子的作用机制进行综述,提高对辣椒碱的研究水平。方法查阅大量国内外文献,总结、提炼并阐明辣椒碱的应用前景。结果辣椒碱具有镇痛、抗癌、心血管保护以及碱脂活性作用。研究发现 T RPV1受体对辣椒碱药效的发挥起到了关键作用。结论预见辣椒碱在抗癌、心血管保护方面有巨大的新药开发前景。%Objective To review the recent pharmacological action and phamacokinetics researches of capsaicin both domestic and abroad . Methods Recent literatures were summarized and analyzed .Result Capsaicin has the analgesic ,anti-cancer ,cardiovascular protective and reducing fat effect .Recent studies found that capsaicin receptor TRPV1 plays a key role in its pharmacological effects .Conclusion It is anticipated that capsaicin has great prospects for new drugs development in anticancer and cardiovascular protection .

  13. Pharmacological Properties of Nanometals (Silver, Copper, Iron

    Directory of Open Access Journals (Sweden)

    Chekman, I.S.

    2015-01-01

    Full Text Available The article summarizes the results of studies on the pharmacological, toxicological and specific properties of nanometals (silver, iron, copper. It is established that nanoparticles of silver, copper, iron exhibit antimicrobial action. Acute toxicity of nanometals depends on their nature, administration route and animal sex. Effects on heart activity and hemodynamic status as well as erythrocyte osmotic fragility have dose-dependent nature.

  14. Conjugation with receptor-targeted histidine-rich peptides enhances the pharmacological effectiveness of antisense oligonucleotides.

    Science.gov (United States)

    Nakagawa, Osamu; Ming, Xin; Carver, Kyle; Juliano, Rudy

    2014-01-15

    Ineffective delivery to intracellular sites of action is one of the key limitations to the use of antisense and siRNA oligonucleotides as therapeutic agents. Here, we describe molecular scale antisense oligonucleotide conjugates that bind selectively to a cell surface receptor, are internalized, and then partially escape from nonproductive endosomal locations to reach their sites of action in the nucleus. Peptides that include bombesin sequences for receptor targeting and a run of histidine residues for endosomal disruption were covalently linked to a splice switching antisense oligonucleotide. The conjugates were tested for their ability to correct splicing and up-regulate expression of a luciferase reporter in prostate cancer cells that express the bombesin receptor. We found that trivalent conjugates that included both the targeting sequence and several histidine residues were substantially more effective than conjugates containing only the bombesin or histidine moieties. This demonstrates the potential of creating molecular scale oligonucleotide conjugates with both targeting and endosome escape capabilities.

  15. World-volume Effective Actions of Exotic Five-branes

    CERN Document Server

    Kimura, Tetsuji; Yata, Masaya

    2014-01-01

    We construct world-volume effective actions of exotic $5^2_2$-branes in type IIA and IIB string theories. The effective actions are given in fully space-time covariant forms with two Killing vectors associated with background isometries. The effective theories are governed by the six-dimensional $\\mathcal{N}=(2,0)$ tensor multiplet and $\\mathcal{N}=(1,1)$ vector multiplet, respectively. Performing the S-duality transformation to the $5^2_2$-brane effective action in type IIB string theory, we also work out the world-volume action of the $5^2_3$-brane. We discuss some additional issues relevant to the exotic five-branes in type I and heterotic string theories.

  16. Let's 'play' with molecular pharmacology.

    Science.gov (United States)

    Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna

    2015-01-01

    Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P pharmacology in undergraduate medical curricula.

  17. Thermodynamics of pharmacological action for electron-accepting compounds on activated or damaged cell in the context of Ling's model of the living cell

    CERN Document Server

    Matveev, V V; Puzyrnikova, N V

    2011-01-01

    The theory describing action of medicines explored in this paper is based on assumption that vital activity of the cell may be described in terms of the model of two states: resting state and excitation. According to available physiological data excitation state is dangerous for cell and may cause different pathological changes, including "conformational" diseases, due to protein aggregation. Normally, the excitation is completely reversible and the key role is played here by ATP (adenosine-5'-triphosphate) which disaggregates proteins of cytomatrix. The same effect ATP exerts during cell injury by eliciting a "healing" effect. Damage of cell structures we consider as "illness", whereas removal of pathological consequences caused by protein aggregation of any origin we will call "a cure". The latter is considered as physical process of cell recovering from excitation/injury to resting state, which is analyzed in terms of our generalized thermodynamics. "Cure" results in reduction of effective temperature of c...

  18. QCD Effective action at high temperature and small chemical potential

    CERN Document Server

    Villavicencio, C

    2007-01-01

    We present a construction of an effective Yang-Mills action for QCD, from the expansion of the fermionic determinant in terms of powers of the chemical potential at high temperature, for the case of massless quarks. We analyze this expansion in the perturbative region and find that it gives extra spurious information. We propose for the non-perturbative sector a simplified effective action which, in principle, contains only the relevant information.

  19. Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2013-08-01

    Full Text Available Jan M Keppel Hesselink Department of Pharmacology, University of Witten/Herdecke, Witten, Germany Abstract: The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957–1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. Keywords: palmitoylethanolamide, sociology, science, paradigm, peroxisome proliferator-activated receptor-alpha, nutraceutical

  20. Effectiveness of the psychological and pharmacological treatment of catastrophization in patients with fibromyalgia: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Magallón Rosa

    2009-04-01

    Full Text Available Abstract Background Fibromyalgia is a prevalent and disabling disorder characterized by widespread pain and other symptoms such as insomnia, fatigue or depression. Catastrophization is considered a key clinical symptom in fibromyalgia; however, there are no studies on the pharmacological or psychological treatment of catastrophizing. The general aim of this study is to assess the effectiveness of cognitive-behaviour therapy and recommended pharmacological treatment for fibromyalgia (pregabalin, with duloxetine added where there is a comorbid depression, compared with usual treatment at primary care level. Method/design Design: A multi-centre, randomized controlled trial involving three groups: the control group, consisting of usual treatment at primary care level, and two intervention groups, one consisting of cognitive-behaviour therapy, and the other consisting of the recommended pharmacological treatment for fibromyalgia. Setting: 29 primary care health centres in the city of Zaragoza, Spain. Sample: 180 patients, aged 18–65 years, able to understand and read Spanish, who fulfil criteria for primary fibromyalgia, with no previous psychological treatment, and no pharmacological treatment or their acceptance to discontinue it two weeks before the onset of the study. Intervention: Psychological treatment is based on the manualized protocol developed by Prof. Escobar et al, from the University of New Jersey, for the treatment of somatoform disorders, which has been adapted by our group for the treatment of fibromyalgia. It includes 10 weekly sessions of cognitive-behaviour therapy. Pharmacological therapy consists of the recommended pharmacological treatment for fibromyalgia: pregabalin (300–600 mg/day, with duloxetine (60–120 mg/day added where there is a comorbid depression. Measurements: The following socio-demographic data will be collected: sex, age, marital status, education, occupation and social class. The diagnosis of psychiatric

  1. Effects of perceived control and cognitive coping on endocrine stress responses to pharmacological activation

    Science.gov (United States)

    Abelson, James L.; Khan, Samir; Liberzon, Israel; Erickson, Thane M.; Young, Elizabeth A.

    2008-01-01

    Background The hypothalamic-pituitary adrenal (HPA) axis may mediate negative health effects of stress. It is sensitive to cognitive/emotional factors like novelty, perceived control and coping. Psychological intervention that reduces novelty, and enhances cognitive coping and sense of control can reduce cortisol responses to pentagastrin, a pharmacological HPA activator. This study attempted to identify the core factors that modulate HPA axis activity in this model. Methods Varying instructions were administered prior to drug exposure in a two-visit (placebo first) pentagastrin infusion paradigm. Healthy subjects (n=40) were randomly assigned to 1 of 4 instruction groups: (1) Standard instruction (SI); (2) Full cognitive intervention (CI); (3) The CI control component alone; or (4) The CI novelty reduction/coping components alone. Blood samples were obtained via intravenous catheter before and after pentagastrin. Results Subjects receiving an intervention had smaller cortisol responses than subjects receiving standard instructions. “Coping” alone had as strong an impact as the more complex intervention that combined “coping” and “control.” “Control alone” also reduced cortisol but its HPA impact appeared less robust. Conclusions Brief psychological manipulation can significantly reduce HPA activation in challenge paradigms. Cognitive preparation that focused on side effects, reduced potential surprise and enhanced cognitive coping modulated HPA axis activity as effectively as a previously tested intervention that combined coping and control manipulations. A sense of control alone also reduced cortisol release. The results support development of “control” or “coping” techniques to combat negative health effects of stress that are mediated by HPA axis activation. PMID:18571624

  2. Effect of pharmacological lowering of plasma urate on exercise-induced oxidative stress.

    Science.gov (United States)

    McAnulty, S R; Hosick, P A; McAnulty, L S; Quindry, J C; Still, L; Hudson, M B; Dibarnardi, A N; Milne, G L; Morrow, J D; Austin, M D

    2007-12-01

    Urate is a metabolic end product of purine metabolism that contributes about 66% of the antioxidant capacity of plasma. The objective of this study was to evaluate the importance of plasma urate as an antioxidant using pharmacological lowering and examining the impact on plasma antioxidant capacity and oxidative stress after intense exercise. Fifteen subjects ran for 45 min at approximately 80% VO2 max under the influence of probenecid (1 g/d) (PRO) or placebo (PLA) in a double-blind, crossover design. Blood samples obtained at baseline, pre-exercise, and immediately post-exercise were analyzed for F2-isoprostanes, lipid hydroperoxides (LHs), ferric-reducing ability of plasma (FRAP), urate, ascorbate (AA), and nitrite. A 2 (group)x2 (time) repeated-measures analysis of variance (ANOVA), one-way ANOVA, Tukey-Kramer multiple comparison tests, and Student's t tests were used for statistical analysis. PRO exhibited lowered urate and FRAP compared with baseline (peffects existed for the exercise trials (p=0.023 and p

  3. Drugs, non-drugs, and disease category specificity: organ effects by ligand pharmacology.

    Science.gov (United States)

    García-Sosa, A T; Maran, U

    2013-01-01

    Important understanding can be gained from using molecular biology-based and chemistry-based techniques together. Bayesian classifiers have thus been developed in the present work using several statistically significant molecular properties of compiled datasets of drugs and non-drugs, including their disease category or organ. The results show they provide a useful classification and simplicity of several different ligand efficiencies and molecular properties. Early recall of drugs among non-drugs using the classifiers as a ranking tool is also provided. As the chemical space of compounds is addressed together with their anatomical characterization, chemical libraries can be improved to select for specific organ or disease. Eventually, by including even finer detail, the method may help in designing libraries with specific pharmacological or toxicological target chemical space. Alternatively, a lack of statistically significant differences in property density distributions may help in further describing compounds with possibility of activity on several organs or disease groups, and given their very similar or considerably overlapping chemical space, therefore wanted or unwanted side-effects. The overlaps between densities for several properties of organs or disease categories were calculated by integrating the area under the curves where they intersect. The naïve Bayesian classifiers are readily built, fast to score, and easily interpretable.

  4. Pharmacological effects of methanolic extract of Swietenia mahagoni Jacq (meliaceae seeds

    Directory of Open Access Journals (Sweden)

    Ghosh Sruti

    2009-01-01

    Full Text Available Seeds of medicinal plants are common ingredients of many folk and herbal medicines, and seed extracts have been reported to possess pharmacological activity including anti-inflammatory activity. In the present investigation, the methanolic extract of the dried ground seeds of Swietenia mahagoni (SMSE has been evaluated for anti-inflammatory, analgesic, and antipyretic activities. The anti-inflammatory activity was evaluated using acute, sub-chronic, and chronic models of inflammation in rodents. The antipyretic and analgesic activities were evaluated in mice models. Acute toxicity studies revealed that the extract up to a dose of 1.2 g/kg intraperitoneally was nontoxic. SMSE at doses of 50 and 100 mg/kg, i.p. was found to possess anti-inflammatory, analgesic, and antipyretic activities and the effect was comparable with that produced by the standard drug, ibuprofen. The results of the experiment on arachidonic acid-induced paw edema in rat revealed that the extract produces anti-inflammatory activity through dual inhibition of the cyclo-oxygenase and lipo-oxygenase pathways of arachidonic acid metabolism. SMSE also enhanced peritoneal cell exudates along with macrophage significantly. The triterpenoids present in SMSE may be responsible for these activities. SMSE possesses anti-inflammatory, analgesic, and antipyretic activities.

  5. Effects of pharmacologic reductions in salivary flow on taste thresholds in man.

    Science.gov (United States)

    Christensen, C M; Navazesh, M; Brightman, V J

    1984-01-01

    The effects of short-term salivary flow reductions on human taste thresholds were measured. Recognition and detection thresholds were obtained from 65 subjects during periods of both normal and reduced salivary flow. Decreased salivary flow was achieved by oral administration of either Elavil, Benadryl or atropine. Thresholds were measured for NaCl, citric acid, quinine sulphate and sucrose with a traditional series of aqueous solutions as well as with a series of dry taste stimuli using a filter-paper base. Whole mouth resting flow and stimulated salivary flow were measured before and after taste testing. The pharmacologic agents produced depressions in salivary flow ranging between 30 and 75 per cent of normal levels. The large decreases in flow produced no measurable changes in taste thresholds with the exception that an increased sensitivity to aqueous and dry citric acid stimuli consistently was observed following atropine administration. Changes in salivary bicarbonate levels, produced by atropine, may have mediated the observed shifts in oral sensitivity to citric acid.

  6. General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). II. Actions on the cardiovascular system, intestinal transit and central nervous system.

    Science.gov (United States)

    Cosnier, D; Hache, J; Labrid, C; Rispat, G

    1976-01-01

    The effects of 1-(2-methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-piperazine-dihydrochloride (zipeprol, 3024 CERM, Respilene), a new nonopiate antitussive agent, have been studied on the cardiovascular system, intestinal function and the central nervous system. Most of these studies were performed comparatively with reference antitussives, particularly codeine, whose activites in these fields are the basis of its undesirable side effects. In the dog, zipeprol showed no hypotensive or cardiac-depressant activity. It did not alter pulmonary arterial pressure. An important antiarrhythmic action was apparent in studies on rhythm disturbances induced by ouabain and coronary ligation. Intestinal function, measured by the recording of peristaltic movements in the dog and the speed of intestinal transit in the rat, was not modified by the product. Zipeprol showed no characteristic action on the central nervous system. Analgesic activity was seen only at doses just below toxic levels. Finally in the rat and the mouse, no evidence of physical dependence was seen after prolonged treatment. This together with the absence of chemical similarity to the morphinics, leads to exclude the possibility of zipeprol treatment leading to addiction. The results of these studies allow zipeprol to be clearly distinguished from the opiate antitussives.

  7. Urban Heat Island Effect Actions - Neighborhood Data

    Data.gov (United States)

    Louisville Metro Government — The urban heat island effect — defined as the difference in temperature between the core of Louisville and its suburbs — contributes to heat-related illnesses and...

  8. Courses of action for effects based operations using evolutionary algorithms

    Science.gov (United States)

    Haider, Sajjad; Levis, Alexander H.

    2006-05-01

    This paper presents an Evolutionary Algorithms (EAs) based approach to identify effective courses of action (COAs) in Effects Based Operations. The approach uses Timed Influence Nets (TINs) as the underlying mathematical model to capture a dynamic uncertain situation. TINs provide a concise graph-theoretic probabilistic approach to specify the cause and effect relationships that exist among the variables of interest (actions, desired effects, and other uncertain events) in a problem domain. The purpose of building these TIN models is to identify and analyze several alternative courses of action. The current practice is to use trial and error based techniques which are not only labor intensive but also produce sub-optimal results and are not capable of modeling constraints among actionable events. The EA based approach presented in this paper is aimed to overcome these limitations. The approach generates multiple COAs that are close enough in terms of achieving the desired effect. The purpose of generating multiple COAs is to give several alternatives to a decision maker. Moreover, the alternate COAs could be generalized based on the relationships that exist among the actions and their execution timings. The approach also allows a system analyst to capture certain types of constraints among actionable events.

  9. General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.

    Science.gov (United States)

    Rispat, G; Burgi, H; Cosnier, D; Duchêne-Marullaz, P; Streichenberger, G

    1976-04-01

    1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.

  10. Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee.

    Science.gov (United States)

    Woods, Beth; Manca, Andrea; Weatherly, Helen; Saramago, Pedro; Sideris, Eleftherios; Giannopoulou, Christina; Rice, Stephen; Corbett, Mark; Vickers, Andrew; Bowes, Matthew; MacPherson, Hugh; Sculpher, Mark

    2017-01-01

    There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture

  11. Effectiveness of team based learning to teach pharmacology for phase-II MBBS students

    Directory of Open Access Journals (Sweden)

    N.K. Hashilkar

    2014-07-01

    Full Text Available Background: TBL (Team based Learning instructional methods foster applying knowledge in a highly interactive setting. Furthermore, in contrast to PBL (Problem Based Learning, it is a teacher directed method that encourages student- student interaction. Objective: The present study is aimed to assess the effectiveness of TBL over the current conventional tutorial type of teaching-learning strategy. Materials and Methods: The present study was conducted in the department of pharmacology of KLE University’s J N Medical College, Belgaum for phase II MBBS students. Students were randomly assigned to either team based learning (TBL or conventional tutorial (CT groups. Teaching learning sessions were conducted on similar topics of cardiovascular system following mechanics of TBL or tutorials respectfully. Effectiveness of each session was assessed by common pre-test and post test while, the overall performance was assessed at the end by a common test for both groups. The scores of the two groups were analysed using students t-test. A feedback was obtained from the students regarding their experience with TBL. Results: There was a significant difference between the pre-CT and pre-TBL scores for Anti-hypertensives (p ≤ 0.0001 and congestive cardiac failure (p ≤0.0002 sessions while these scores were not significantly different for Anti-anginals and Renin angiotensin system. However, the comparison of post-CT and post-TBL scores were significantly different (p< 0.05 for each of the four sessions. The scores of the end of the module test showed significant difference (p <0.0001 between the two group. Most of the students appreciated the mechanics of TBL and were satisfied with it. Conclusions: The performance of the students of the TBL group improved in individual sessions as well as the entire module as opposed to the CT group.

  12. A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects

    Directory of Open Access Journals (Sweden)

    Sidney J. Stohs

    2011-01-01

    Full Text Available Bitter orange (Citrus aurantium extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine, and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.

  13. Renormalization and effective actions for general relativity

    Energy Technology Data Exchange (ETDEWEB)

    Neugebohrn, F.

    2007-05-15

    Quantum gravity is analyzed from the viewpoint of the renormalization group. The analysis is based on methods introduced by J. Polchinski concerning the perturbative renormalization with flow equations. In the first part of this work, the program of renormalization with flow equations is reviewed and then extended to effective field theories that have a finite UV cutoff. This is done for a scalar field theory by imposing additional renormalization conditions for some of the nonrenormalizable couplings. It turns out that one so obtains a statement on the predictivity of the effective theory at scales far below the UV cutoff. In particular, nonrenormalizable theories can be treated without problems in the proposed framework. In the second part, the standard covariant BRS quantization program for Euclidean Einstein gravity is applied. A momentum cutoff regularization is imposed and the resulting violation of the Slavnov-Taylor identities is discussed. Deriving Polchinski's renormalization group equation for Euclidean quantum gravity, the predictivity of effective quantum gravity at scales far below the Planck scale is investigated with flow equations. A fine-tuning procedure for restoring the violated Slavnov-Taylor identities is proposed and it is argued that in the effective quantum gravity context, the restoration will only be accomplished with finite accuracy. Finally, the no-cutoff limit of Euclidean quantum gravity is analyzed from the viewpoint of the Polchinski method. It is speculated whether a limit with nonvanishing gravitational constant might exist where the latter would ultimatively be determined by the cosmological constant and the masses of the elementary particles. (orig.)

  14. Integrating pharmacology and clinical pharmacology in universities.

    Science.gov (United States)

    Buckingham, Julia C

    2012-06-01

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

  15. The influence of women's attachment style on the chronobiology of labour pain, analgesic consumption and pharmacological effect.

    Science.gov (United States)

    Costa-Martins, José Manuel; Pereira, Marco; Martins, Henriqueta; Moura-Ramos, Mariana; Coelho, Rui; Tavares, Jorge

    2014-07-01

    Circadian variation in biological rhythms has been identified as affecting both labour pain and the pharmacological properties of analgesics. In the context of pain, there is also a growing body of evidence suggesting the importance of adult attachment. The purpose of this study was to examine whether labour pain, analgesic consumption and pharmacological effect are significantly affected by the time of day and to analyse whether this circadian variation is influenced by women's attachment style. This prospective observational study included a sample of 81 pregnant women receiving patient-controlled epidural analgesia (PCEA). Attachment was assessed with the Adult Attachment Scale - Revised. The perceived intensity of labour pain in the early stage of labour (3 cm of cervical dilatation and before the administration of PCEA) was measured using a visual analogue scale (VAS). Pain was also indirectly assessed by measuring the consumption of anaesthetics. The latency period and the duration of effect were recorded for a chronopharmacology characterisation. Pain, as assessed with the VAS, was significantly higher in the night-time group than in the daytime group. An insecure attachment style was significantly associated with greater labour pain at 3 cm of cervical dilatation (p < 0.001) and before the beginning of analgesia (p < 0.001) as well as with higher analgesic consumption and lower pharmacological efficacy (p < 0.05). The time of day was significantly associated with the pharmacological effect: the latency period was longer at night, and the duration of the pharmacological effect was longer during the daytime. The interaction between time of day and attachment style was not significant for any of the study variables. Our results provide evidence of the importance of circadian variation in studying labour pain and the pharmacological effect of labour analgesia involving epidural blockage with a PCEA regimen. Moreover, although there was no

  16. In Silico Systems Pharmacology to Assess Drug's Therapeutic and Toxic Effects

    DEFF Research Database (Denmark)

    Orozco, Alejandro Aguayo; Audouze, Karine; Brunak, Soren

    2016-01-01

    For many years, the "one target, one drug" paradigm has been the driving force behind developments in pharmaceutical research. With the recent advances in molecular biology and genomics technologies, the focus is shifting toward "drug-holistic" systems based approaches (i.e. systems pharmacology......). The integration of large and diverse amount of data from chemistry and biology coupled with the development and the application of network-based approaches to cope with these data is the next paradigm of drug discovery. Systems pharmacology offers a novel way of approaching drug discovery by developing models...

  17. Perception, action, and Roelofs effect: a mere illusion of dissociation.

    Directory of Open Access Journals (Sweden)

    Paul Dassonville

    2004-11-01

    Full Text Available A prominent and influential hypothesis of vision suggests the existence of two separate visual systems within the brain, one creating our perception of the world and another guiding our actions within it. The induced Roelofs effect has been described as providing strong evidence for this perception/action dissociation: When a small visual target is surrounded by a large frame positioned so that the frame's center is offset from the observer's midline, the perceived location of the target is shifted in the direction opposite the frame's offset. In spite of this perceptual mislocalization, however, the observer can accurately guide movements to the target location. Thus, perception is prone to the illusion while actions seem immune. Here we demonstrate that the Roelofs illusion is caused by a frame-induced transient distortion of the observer's apparent midline. We further demonstrate that actions guided to targets within this same distorted egocentric reference frame are fully expected to be accurate, since the errors of target localization will exactly cancel the errors of motor guidance. These findings provide a mechanistic explanation for the various perceptual and motor effects of the induced Roelofs illusion without requiring the existence of separate neural systems for perception and action. Given this, the behavioral dissociation that accompanies the Roelofs effect cannot be considered evidence of a dissociation of perception and action. This indicates a general need to re-evaluate the broad class of evidence purported to support this hypothesized dissociation.

  18. Boldine action against the stannous chloride effect.

    Science.gov (United States)

    Reiniger, I W; Ribeiro da Silva, C; Felzenszwalb, I; de Mattos, J C; de Oliveira, J F; da Silva Dantas, F J; Bezerra, R J; Caldeira-de-Araújo, A; Bernardo-Filho, M

    1999-12-15

    Peumus boldus extract has been used in popular medicine in the treatment of biliar litiase, hepatic insufficiency and liver congestion. Its effects are associated to the substance boldine that is present in its extract. In the present work, we evaluated the influence of boldine both in: (i) the structural conformation of a plasmid pUC 9.1 through gel electrophoresis analysis; and in (ii) the survival of the strain of Escherichia coli AB1157 submitted to reactive oxygen species (ROS), generated by a Fenton like reaction, induced by stannous chloride. Our results show a reduction of the lethal effect induced by stannous chloride on the survival of the E. coli culture in the presence of boldine. The supercoiled form of the plasmid is not modified by stannous chloride in the presence of boldine. We suggest that the protection induced by boldine could be explained by its anti-oxidant mechanism. In this way, the boldine could be reacting with stannous ions, protecting them against the oxidation and, consequently, avoiding the generation of ROS.

  19. Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).

    Science.gov (United States)

    Kampa, Marilena; Notas, George; Pelekanou, Vassiliki; Troullinaki, Maria; Andrianaki, Maria; Azariadis, Kalliopi; Kampouri, Errika; Lavrentaki, Katerina; Castanas, Elias

    2012-08-01

    The complexity of estrogen actions mainly relies to the presence of different identified receptors (ERα, ERβ, their isoforms, and GPR30/GPER) and their discrete cellular distribution. Depending on the localization of the receptor that mediates estrogen effects, nuclear and extra-nuclear actions have been described. The latter can trigger a number of signaling events leading also to transcriptional modifications. In an attempt to clarify the nature of the receptor(s) involved in the membrane initiated effect of estrogens on gene expression, we performed a whole transcriptome analysis of breast cancer cell lines with different receptor profiles (T47D, MCF7, MDA-MB-231, SK-BR-3). A pharmacological approach was conducted with the use of estradiol (E(2)) or membrane-impermeable E(2)-BSA in the absence or presence of a specific ERα-β or GPR30/GPER antagonist. Our results clearly show that in addition to the ERα isoforms and/or GPR30/GPER that mainly mediate the transcriptional effect of E(2)-BSA, there is a specific transcriptional signature (found in T47D and MCF-7 cells) suggesting the presence of an unidentified membrane ER element (ERx). Analysis of its signature and phenotypic verification revealed that important cell function such as apoptosis, transcriptional regulation, and growth factor signaling are associated with ERx. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Effective Action of Softly Broken Supersymmetric Theories

    CERN Document Server

    Nibbelink, S G; Nibbelink, Stefan Groot; Nyawelo, Tino S.

    2007-01-01

    We study the renormalization of (softly) broken supersymmetric theories at the one loop level in detail. We perform this analysis in a superspace approach in which the supersymmetry breaking interactions are parameterized using spurion insertions. We comment on the uniqueness of this parameterization. We compute the one loop renormalization of such theories by calculating superspace vacuum graphs with multiple spurion insertions. To preform this computation efficiently we develop algebraic properties of spurion operators, that naturally arise because the spurions are often surrounded by superspace projection operators. Our results are general apart from the restrictions that higher super covariant derivative terms and some finite effects due to non-commutativity of superfield dependent mass matrices are ignored. One of the soft potentials induces renormalization of the Kaehler potential.

  1. Research Progress about Pharmacological Effect and Mechanism of Flavonoids in Traditional Chinese Medicine%中药黄酮类化合物药理作用及作用机制研究进展

    Institute of Scientific and Technical Information of China (English)

    马锐; 吴胜本

    2013-01-01

    目的 对黄酮类化合物的药理作用及其作用机制进行综述和分析.方法 对近年来有关黄酮类化合物的药理作用及其作用机制的文献进行总结与分析.结果 黄酮类化合物具有抗氧化、抗炎、镇痛、调节免疫、抗衰老、降血脂、抗肿瘤等药理作用,其作用机制可能与其抗自由基或抗氧化有关.结论 黄酮类化合物是许多中草药的有效成分,具有广泛的生物活性,其产生生物活性的作用机制有待于进一步深入的研究.%Objective To review and analyze the pharmacological effect and mechanism of flavonoids in traditional Chinese medicine. Methods The related references in recent years home and abroad about the pharmacological effect and mechanism of flavonoids in traditional Chinese medicine were summarized and analyzed. Results Flavonoids had a wide range of pharmacological effects such as antioxidant, anti-inflammatory and analgesic, regulating immunity, anti-aging, fall hematic fat, antitumor and pharmacological action and so on, and the mechanism of pharmacological effects may be related with the resistance to free radicals or antioxidant. Conclusion The flavonoid compounds were the effective composition of many Chinese herbal medicine, and had a wide range of biological activity, and its biological activity mechanism needed further in-depth research.

  2. Non-dissipative hydrodynamics: effective actions versus entropy current

    Science.gov (United States)

    Bhattacharya, Jyotirmoy; Bhattacharyya, Sayantani; Rangamani, Mukund

    2013-02-01

    While conventional hydrodynamics incorporating dissipative effects is hard to derive from an action principle, it is nevertheless possible to construct classical actions when the dissipative terms are switched off. In this note we undertake a systematic exploration of such constructions from an effective field theory approach and argue for the existence of non-trivial second order non-dissipative hydrodynamics involving pure energy-momentum transport. We find these fluids to be characterized by five second-order transport coefficients based on the effective action (a three parameter family is Weyl invariant). On the other hand since all flows of such fluids are non-dissipative, they entail zero entropy production; one can therefore understand them using the entropy current formalism which has provided much insight into hydrodynamic transport. An analysis of the most general stress tensor with zero entropy production however turns out to give a seven parameter family of non-dissipative hydrodynamics (a four parameter sub-family being Weyl invariant). The non-dissipative fluids derived from the effective action approach are a special case of the fluid dynamics constrained by conservation of the entropy current. We speculate on the reasons for the mismatch and potential limitations of the effective action approach.

  3. Effective Actions of Matrix Models on Homogeneous Spaces

    CERN Document Server

    Imai, T; Takayama, Y; Tomino, D

    2002-01-01

    We evaluate the effective actions of supersymmetric matrix models on fuzzy S^2times S^2 up to the two loop level. Remarkably it turns out to be a consistent solution of IIB matrix model. Based on the power counting and SUSY cancellation arguments, we can identify the 't Hooft coupling and large N scaling behavior of the effective actions to all orders. In the large N limit, the quantum corrections survive except in 2 dimensional limits. They are O(N) and O(N^{4over 3}) for 4 and 6 dimensional spaces respectively. We argue that quantum effects single out 4 dimensionality of space-time.

  4. Truncation Effects in Monte Carlo Renormalization Group Improved Lattice Actions

    CERN Document Server

    Takaishi, T; Forcrand, Ph. de

    1998-01-01

    We study truncation effects in the SU(3) gauge actions obtained by the Monte Carlo renormalization group method. By measuring the heavy quark potential we find that the truncation effects in the actions coarsen the lattice by 40-50 % from the original blocked lattice. On the other hand, we find that rotational symmetry of the heavy quark potentials is well recovered on such coarse lattices, which may indicate that rotational symmetry breaking terms are easily cancelled out by adding a short distance operator. We also discuss the possibility of reducing truncation effects.

  5. One-loop effective action in quantum gravitation

    DEFF Research Database (Denmark)

    Rachwal, Leslaw; Codello, Alessandro; Percacci, Roberto

    2016-01-01

    We present the formalism of computing one-loop effective action for Quantum Gravitation using non-local heat kernel methods. We found agreement with previous old results. In main part of my presentation I considered the system of E-H gravitation and scalar fields. We were able to derive non......-local quantum effective action up to the second order in heat kernel generalized curvatures. By going to flat spacetime expressions for gravitational form factors are possible to construct and compare with the results from effective field theory for gravity....

  6. Early markers of ongoing action-effect learning.

    Science.gov (United States)

    Ruge, Hannes; Krebs, Ruth M; Wolfensteller, Uta

    2012-01-01

    Acquiring knowledge about the relationship between stimulus conditions, one's own actions, and the resulting consequences or effects, is one prerequisite for intentional action. Previous studies have shown that such contextualized associations between actions and their effects (S-R-E associations) can be picked up very quickly. The present study examined how such weakly practiced associations might affect overt behavior during the process of initial learning and during subsequent retrieval, and how these two measures are inter-related. We examined incidental (S-)R-E learning in the context of trial-and-error S-R learning and in the context of instruction-based S-R learning. Furthermore, as a control condition, common outcome (CO) learning blocks were included in which all responses produced one common sound effect, hence precluding differential (S-)R-E learning. Post-learning retrieval of R-E associations was tested by re-using previously produced sound effects as novel imperative stimuli combined with actions that were either compatible or incompatible with the previously encountered R-E mapping. The central result was that the size of the compatibility effect could be predicted by the size of relative response slowing during ongoing learning in the preceding acquisition phase, both in trial-and-error learning and in instruction-based learning. Importantly, this correlation was absent for the CO control condition, precluding accounts based on unspecific factors. Instead, the results suggest that differential outcomes are "actively" integrated into action planning and that this takes additional planning time. We speculate that this might be especially true for weakly practiced (S-)R-E associations before an initial goal-directed action mode transitions into a more stimulus-based action mode.

  7. Early markers of ongoing action-effect learning

    Directory of Open Access Journals (Sweden)

    Hannes eRuge

    2012-11-01

    Full Text Available Acquiring knowledge about the relationship between stimulus conditions, one’s own actions, and the resulting consequences or effects, is one prerequisite for intentional action. Previous studies have shown that such contextualized associations between actions and their effects (S-R-E associations can be picked up very quickly. The present study examined how such weakly practiced associations might affect overt behavior during the process of initial learning and during subsequent retrieval, and how these two measures are inter-related. We examined incidental (S-R-E learning in the context of trial-and-error S-R learning and in the context of instruction-based S-R learning. Furthermore, as a control condition, common outcome (CO learning blocks were included in which all responses produced one common sound effect, hence precluding differential (S-R-E learning. Post-learning retrieval of R-E associations was tested by re-using previously produced sound effects as novel imperative stimuli combined with actions that were either compatible or incompatible with the previously encountered R-E mapping. The central result was that the size of the compatibility effect could be predicted by the size of relative response slowing during ongoing learning in the preceding acquisition phase, both in trial-and-error learning and in instruction-based learning. Importantly, this correlation was absent for the common outcome control condition, precluding accounts based on unspecific factors. Instead, the results suggest that differential outcomes are ‘actively’ integrated into action planning and that this takes additional planning time. We speculate that this might be especially true for weakly practiced (S-R-E associations before an initial goal-directed action mode transitions into a more stimulus-based action mode.

  8. The Geometric Construction of WZW Effective Action in Noncommutative Manifold

    Institute of Scientific and Technical Information of China (English)

    HOU BoYu; WANG YongQiang; YANG ZhanYing; YUE RuiHong

    2002-01-01

    By constructing close-one-cochain density in the gauge group space we get the Wess Zumino Witten(WZW) effective Lagrangian on high-dimensional noncommutative space. Especially consistent anomalies derived fromthis WZW effective action in noncommutative four-dimensional space coincide with those obtained by L. Bonora etc.(hep-th /0002210).

  9. The Geometric Construction of WZW Effective Action in Noncommutative Manifold

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    By constructing close-one-cochain density Ω12n in the gauge group space we get the Wess-Zumino-Witten (WZW) effective Lagrangian on high-dimensional noncommutative space.Especially consistent anomalies derived from this WZW effective action in noncommutative four-dimensional space coincide with those obtained by L.Bonora etc.(het-th/0002210).

  10. N,N-diethyl-4-aminoazobenzene (DEAB): acute actions with respect to possible carcinogenicity as well as the role of solvents. Morphological and pharmacological investigations.

    Science.gov (United States)

    Danz, M; Klinger, W; Müller, D; Kleeberg, U; Glöckner, R; Ziebarth, D; Urban, H

    1978-01-01

    The acute action of the azo dye DEAB was investigated in Sprague-Dawley (SD) and Wistar (Wi) rats. The substance was dissolved both in DMSO and sunflower oil and was administered once by stomach tube. Cytochrome P-450-DEPENDENT N-demethylation of ethylmorphine and dimethylnitrosamine are differentially altered depending on the solvent used. The excretion of DEAB as well as of N,N-dimethyl-4-amino-azobenzene (DAB) is delayed and diminished if the substances are dissolved in DMSO. Beside these effects the mitotic number in the adrenal cortex is significantly elevated in both strains of rats. But, in SD rats only DMSO-solution of DEAB is effective. In Wi rats both are effective, the oily solution more than that in DMSO. In this respect DEAB resembles DAB and various other carcinogens which are efficient in stimulating adrenocortical cell division. Considering the positive short-term assay after three other substances which revealed carcinogenic properties in long-term experiments we conclude that also DEAB may be carcinogenic in adequate long-term examination.

  11. Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin’s Anorectic Signaling Actions

    Science.gov (United States)

    Gao, Su; Howard, Shannon; LoGrasso, Philip V.

    2017-01-01

    The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-JNK (JNK1/2/3) inhibitor, reduced food intake and body weight. Moreover, i.p. and i.c.v. administrations of SR11935, a brain-penetrant and JNK2/3 isoform-selective inhibitor, exerted similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR3306 (7 days) prevented the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice. In the DIO mice, JNK inhibition sensitized leptin’s anorectic effect, and enhanced leptin-induced STAT3 activation in the hypothalamus. The underlying mechanisms likely involve the downregulation of SOCS3 by JNK inhibition. Collectively, our data suggest that JNK activity promotes positive energy balance, and the therapeutic intervention inhibiting JNK activities represents a promising approach to ameliorate diet-induced obesity and leptin resistance. PMID:28165482

  12. 水飞蓟素药理作用研究进展%Research Progress in Pharmacological Effects of Silymarin

    Institute of Scientific and Technical Information of China (English)

    刘志刚; 李雪玲; 翁立冬; 刘强; 朱红霞; 黄志刚

    2012-01-01

    Objective : To introduce the research progress in pharmacological effects and provide theoretical basis for the research of Silymarin. Methods : It arranged, analyzed and induced the related papers in recent years, the related pharmacological effects research of Silymarin were reviewed. Conclusion: The pharmacological effects of Silymarin are anti hepatic fibrosis, anti renal tubulointerstitial fibrosis, antitumor, anti-inflammation and treating diabetic. Silymarin has good development prospect in the development of new products.%目的:介绍水飞蓟素的药理研究进展,为水飞蓟素的研究提供理论依据.方法:对近几年的相关论文进行整理、分析和归纳,对水飞蓟素的相关药理作用研究进行综述.结果:水飞蓟素具有抗肝纤维化、抗肾小管间质纤维化、抗肿瘤、抗炎及治疗糖尿病的作用.在开发新药方面具有良好的发展前景.

  13. Phthalocyanine photodynamic therapy: disparate effects of pharmacologic inhibitors on cutaneous photosensitivity and on tumor regression.

    Science.gov (United States)

    Anderson, C; Hrabovsky, S; McKinley, Y; Tubesing, K; Tang, H P; Dunbar, R; Mukhtar, H; Elmets, C A

    1997-05-01

    -induced cutaneous photosensitivity. None of these agents had any effect on Pc 4 PDT-induced tumor regression. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies may be valuable pharmacologic agents in the management of cutaneous photosensitivity associated with PDT without altering the efficacy of this new therapeutic modality. The findings suggest that it should be possible to devise PDT protocols that block cutaneous photosensitivity without impairing the anti-tumor response to the agents.

  14. Power effects on cognitive control: Turning conflict into action.

    Science.gov (United States)

    Schmid, Petra C; Kleiman, Tali; Amodio, David M

    2015-06-01

    Power is known to promote effective goal pursuit, especially when it requires one to overcome distractions or bias. We proposed that this effect involves the ability to engage and implement cognitive control. In Study 1, we demonstrated that power enhances behavioral performance on a response conflict task and that it does so by enhancing controlled processing rather than by reducing automatic processing. In Study 2, we used an event-related potential index of anterior cingulate activity to test whether power effects on control were due to enhanced conflict sensitivity or action implementation. Power did not significantly affect neural sensitivity to conflict; rather, high power was associated with a stronger link between conflict processing and intended action, relative to low power. These findings suggest a new perspective on how social factors can affect controlled processing and offer new evidence regarding the transition between conflict detection and the implementation of action control.

  15. Non-dissipative hydrodynamics: Effective actions versus entropy current

    CERN Document Server

    Bhattacharya, Jyotirmoy; Rangamani, Mukund

    2012-01-01

    While conventional hydrodynamics incorporating dissipative effects is hard to derive from an action principle, it is nevertheless possible to construct classical actions when the dissipative terms are switched off. In this note we undertake a systematic exploration of such constructions from an effective field theory approach and argue for the existence of non-trivial second order non-dissipative hydrodynamics involving pure energy-momentum transport. We find these fluids to be characterized by five second-order transport coefficients based on the effective action (a three parameter family is Weyl invariant). On the other hand since all flows of such fluids are non-dissipative, they entail zero entropy production; one can therefore understand them using the entropy current formalism which has provided much insight into hydrodynamic transport. An analysis of the most general stress tensor with zero entropy production however turns out to give a seven parameter family of non-dissipative hydrodynamics (a four pa...

  16. Vacuum States in 2D Tachyon Effective Action

    CERN Document Server

    Kluson, J

    2004-01-01

    In this paper we will study the ground states of the toy model of 2D closed string tachyon effective action. We will firstly construct the classical solutions of the tachyon effective action that do not induce backreaction on metric and dilaton. Then we will study the quantum mechanics of the zero mode of the tachyon field. We will find family of vacuum states labelled with single parameter. We will also perform the quantum mechanical analysis of the tachyon effective action when we take into account dynamics of nonzero modes. We will calculate the vacuum expectation values of components of the stress energy tensor and dilaton source and we will argue that there is not any backreaction on metric and dilaton.

  17. Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical.

    Science.gov (United States)

    Hesselink, Jan M Keppel

    2013-01-01

    The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA) and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957-1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound.

  18. Effect of metal ions on some pharmacologically relevant interactions involving fluoroquinolone antibiotics.

    Science.gov (United States)

    Seedher, Neelam; Agarwal, Pooja

    2010-01-01

    molecule. Results indicate that metal chelate formation can cause significant reduction in the antimicrobial activity of fluoroquinolone antibiotics. Alteration in the HSA-fluoroquinolone binding affinity in the presence of metal ions could have significant pharmacological effects. Quantitative estimate of the magnitude of interaction of different metal ions could also be obtained from the data.

  19. 2PI effective action and gauge invariance problems

    OpenAIRE

    Carrington, M. E.; Kunstatter, G.; Zaraket, H.

    2003-01-01

    The problem of maintaining gauge invariance when truncating the two particle irreducible (2PI) effective action has been studied recently by several authors. Here we give a simple and very general derivation of the gauge dependence identities for the off-shell 2PI effective action. We consider the case where the gauge is fixed by an arbitrary function of the quantum gauge field, subject only to the restriction that the Faddeev-Popov matrix is invertable. We also study the background field gau...

  20. Duality, Monodromy and Integrability of Two Dimensional String Effective Action

    CERN Document Server

    Das, A; Melikyan, A; Das, Ashok

    2002-01-01

    The monodromy matrix, ${\\hat{\\cal M}}$, is constructed for two dimensional tree level string effective action. The pole structure of ${\\hat{\\cal M}}$ is derived using its factorizability property. It is found that the monodromy matrix transforms non-trivially under the non-compact T-duality group, which leaves the effective action invariant and this can be used to construct the monodromy matrix for more complicated backgrounds starting from simpler ones. We construct, explicitly, ${\\hat{\\cal M}}$ for the exactly solvable Nappi-Witten model, both when B=0 and $B\

  1. Boundary Conditions for NHEK through Effective Action Approach

    Institute of Scientific and Technical Information of China (English)

    CHEN Bin; NING Bo; ZHANG Jia-Ju

    2012-01-01

    We study the asymptotic symmetry group (ASG) of the near horizon geometry of extreme Kerr black hole through the effective action approach developed by Porfyriadis and Wilczek (arXiv:1007.1031v1[gr qc]).By requiring a finite boundary effective action,we derive a new set of asymptotic Killing vectors and boundary conditions,which are much more relaxed than the ones proposed by Matsuo Y et al.[Nucl.Phys.B 825 (2010) 231],and still allow a copy of a conformal group as its ASG.In the covariant formalism,the asymptotic charges are finite,with the corresponding central charge vanishing.By using the quasi-local charge and introducing a plausible cut-off,we find that the higher order terms of the asymptotic Killing vectors,which could not be determined through the effective action approach,contribute to the central charge as well.We also show that the boundary conditions suggested by Guica et al.[Phys.Rev.D 80 (2009)124008] lead to a divergent first-order boundary effective action.%We study the asymptotic symmetry group (ASG) of the near horizon geometry of extreme Kerr black hole through the effective action approach developed by Porfyriadis and Wilczek (arXiv:1007.1031vl[gr qc]). By requiring a finite boundary effective action, we derive a new set of asymptotic Killing vectors and boundary conditions, which are much more relaxed than the ones proposed by Matsuo Y et al. [Nucl. Phys. B 825 (2010) 231], and still allow a copy of a conformal group as its ASG. In the covariant formalism, the asymptotic charges are finite, with the corresponding central charge vanishing. By using the quasi-local charge and introducing a plausible cut-off, we find that the higher order terms of the asymptotic Killing vectors, which could not be determined through the effective action approach, contribute to the central charge as well. We also show that the boundary conditions suggested by Guica et al. [Phys. Rev. D 80 (2009) 124008] lead to a divergent first-order boundary effective action.

  2. 水蛭药理作用的研究进展%Research progress on pharmacological effects of Hirudo

    Institute of Scientific and Technical Information of China (English)

    杨洪雁; 杜智恒; 白秀娟

    2012-01-01

    Hirudo is a traditional Chinese medicine with many different pharmacological effects. With the development of technology and further study, Hirudo has been widely applied to the clinical, for good medical prospects. This paper reviewed the research progress on the pharmacological of Hirudo.%水蛭是一味传统的中药,具有多种药理作用.随着技术的发展、研究的日益深入,水蛭越来越广泛的应用于临床,有着良好的医学应用前景.文章综述了水蛭的药理作用的研究进展.

  3. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Directory of Open Access Journals (Sweden)

    Karoline Koch

    2014-01-01

    Full Text Available Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research.

  4. Computing the effective action with the functional renormalization group

    DEFF Research Database (Denmark)

    Codello, Alessandro; Percacci, Roberto; Rachwał, Lesław

    2016-01-01

    The “exact” or “functional” renormalization group equation describes the renormalization group flow of the effective average action Γ k. The ordinary effective action Γ 0 can be obtained by integrating the flow equation from an ultraviolet scale k= Λ down to k= 0. We give several examples of such...... of QED and of Yang–Mills theory. We also compute the two-point functions for scalars and gravitons in the effective field theory of scalar fields minimally coupled to gravity.......The “exact” or “functional” renormalization group equation describes the renormalization group flow of the effective average action Γ k. The ordinary effective action Γ 0 can be obtained by integrating the flow equation from an ultraviolet scale k= Λ down to k= 0. We give several examples...... of such calculations at one-loop, both in renormalizable and in effective field theories. We reproduce the four-point scattering amplitude in the case of a real scalar field theory with quartic potential and in the case of the pion chiral Lagrangian. In the case of gauge theories, we reproduce the vacuum polarization...

  5. 75 FR 10488 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-08

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  6. 78 FR 42966 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-07-18

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  7. 78 FR 58315 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  8. 77 FR 41790 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  9. 75 FR 11551 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-11

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  10. 77 FR 42746 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-20

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  11. 78 FR 58314 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  12. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-06-29

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and...

  13. Anomalous effective action, Noether current, Virasoro algebra and Horizon entropy

    Energy Technology Data Exchange (ETDEWEB)

    Majhi, Bibhas Ranjan [IUCAA, Ganeshkhind, Pune University Campus, Post Bag 4, Pune (India); Hebrew University of Jerusalem, Racah Institute of Physics, Jerusalem (Israel); Chakraborty, Sumanta [IUCAA, Ganeshkhind, Pune University Campus, Post Bag 4, Pune (India)

    2014-05-15

    Several investigations show that in a very small length scale there exist corrections to the entropy of black hole horizon. Due to fluctuations of the background metric and the external fields the action incorporates corrections. In the low energy regime, the one-loop effective action in four dimensions leads to trace anomaly. We start from the Noether current corresponding to the Einstein-Hilbert plus the one-loop effective action to calculate the charge for the diffeomorphisms which preserve the Killing horizon structure. Then a bracket for the charges is calculated. We show that the Fourier modes of the bracket are exactly similar to the Virasoro algebra. Then using the Cardy formula the entropy is evaluated. Finally, the explicit terms of the entropy expression is calculated for a classical background. It turns out that the usual expression for the entropy; i.e. the Bekenstein-Hawking form, is not modified. (orig.)

  14. Effective action approach to wave propagation in scalar QED plasmas

    CERN Document Server

    Shi, Yuan; Qin, Hong

    2016-01-01

    A relativistic quantum field theory with nontrivial background fields is developed and applied to study waves in plasmas. The effective action of the electromagnetic 4-potential is calculated ab initio from the standard action of scalar QED using path integrals. The resultant effective action is gauge invariant and contains nonlocal interactions, from which gauge bosons acquire masses without breaking the local gauge symmetry. To demonstrate how the general theory can be applied, we study a cold unmagnetized plasma and a cold uniformly magnetized plasma. Using these two examples, we show that all linear waves well-known in classical plasma physics can be recovered from relativistic quantum results when taking the classical limit. In the opposite limit, classical wave dispersion relations are modified substantially. In unmagnetized plasmas, longitudinal waves propagate with nonzero group velocities even when plasmas are cold. In magnetized plasmas, anharmonically spaced Bernstein waves persist even when plasma...

  15. 木香生品与麸煨品的药效研究%Pharmacologic Action of Aucklandia lappa and Processed Products

    Institute of Scientific and Technical Information of China (English)

    许枬; 陈懿竹; 战宏利; 张宏达

    2012-01-01

    目的:研究木香生品和麸煨品不同极性部位的药理作用.方法:SPF级雄性SD大鼠,随机分为10组.大鼠禁食(不禁水)24h后,各组口服给予生理盐水、木香生品水煎液(2,6 g·kg-1)、麦麸制木香水煎液(2,6 g·kg-1)、木香生品挥发油(2,6 g·kg-1)、麦麸制木香挥发油(2,6 g·kg-1),1h后采用盐酸-乙醇所致大鼠胃黏膜急性损伤模型,考察木香及其麸制品对胃肠功能的影响.结果:木香生品及其麸制品的挥发油(2,6 g·kg-1)均可显著降低盐酸-乙醇所致大鼠胃黏膜溃疡指数(P<0.01),而且木香麸煨品的高剂量挥发油对大鼠胃黏膜损伤保护作用强于生品(P<0.05).木香麸制前后(2,6 g·kg-1)对盐酸-乙醇所致胃黏膜损伤大鼠的胃泌素分泌量影响较小,只有木香生品(2 9·kg“)有增加胃泌素含量作用(P<0.01).结论:木香麸煨后对大鼠胃黏膜损伤的保护作用增强.%Objective; To study the pharmacology effect of different polar extracts from Aucklandia lappa and its processed products. Method; The stomach mucous membrane injury model induced by hydrochloric acid-alcohol was adopted. SD rats were divided randomly into control group , model group, A. lappa group (2, 6 g-kg"1) , processed products ol A. lappa group (2, 6 g·kg-1') , volatile oil group from A. lappa (2, 6 g·kg-1) , volatile oil of processed products from A. lappa group ( 2, 6 g · kg-1 ) , the gastric percentage was calculated. Result: The essential oil of processed products from A. lappa and A. lappa (2, 6g·kg-1) significantly inhibited the injuries of gastrointestinal mucous membrane (P<0.01), and the activity of essential oil of processed products of A. lappa (6 g·kg-1) was stronger than A., lappa (6 g·kg-1). However, the influence of A. lappa on rats'gastrin was not remarkable, only essential oil of A. lappa ( 2g ?kg-1) exhibited enhance of rats' gastrin. Conclusion: The essential oil of A. lappa may hence the inhibition effect on injuriy of

  16. Action Research: Effective Marketing Strategies for a Blended University Program

    Science.gov (United States)

    Cook, Ruth Gannon; Ley, Kathryn

    2008-01-01

    This action research study investigated a marketing plan based on collaboration among a program faculty team and other organizational units for a graduate professional program. From its inception through the second year of operation, program enrollment increased due to the marketing plan based on an effective approach grounded in simple marketing…

  17. Effects of Action Relations on the Configural Coding between Objects

    Science.gov (United States)

    Riddoch, M. J.; Pippard, B.; Booth, L.; Rickell, J.; Summers, J.; Brownson, A.; Humphreys, G. W.

    2011-01-01

    Configural coding is known to take place between the parts of individual objects but has never been shown between separate objects. We provide novel evidence here for configural coding between separate objects through a study of the effects of action relations between objects on extinction. Patients showing visual extinction were presented with…

  18. Solution-generating transformations and the string effective action

    NARCIS (Netherlands)

    Bergshoeff, E; Janssen, B; Ortin, T

    1996-01-01

    We study exhaustively the solution-generating transformations (dualities) that occur in the context of the low-energy effective action of superstring theory. We first consider target-space duality ('T duality') transformations in the absence of vector fields. We find that for one isometry the full d

  19. The background effective average action approach to quantum gravity

    DEFF Research Database (Denmark)

    D’Odorico, G.; Codello, A.; Pagani, C.

    2016-01-01

    of an UV attractive non-Gaussian fixed-point, which we find characterized by real critical exponents. Our closure method is general and can be applied systematically to more general truncations of the gravitational effective average action. © Springer International Publishing Switzerland 2016....

  20. Action Research: Effective Marketing Strategies for a Blended University Program

    Science.gov (United States)

    Cook, Ruth Gannon; Ley, Kathryn

    2008-01-01

    This action research study investigated a marketing plan based on collaboration among a program faculty team and other organizational units for a graduate professional program. From its inception through the second year of operation, program enrollment increased due to the marketing plan based on an effective approach grounded in simple marketing…

  1. Two-Loop Gluon Regge Trajectory from Lipatov's Effective Action

    CERN Document Server

    Chachamis, Grigorios; Madrigal, José Daniel; Vera, Agustín Sabio

    2012-01-01

    Lipatov's high-energy effective action is a useful tool for computations in the Regge limit beyond leading order. Recently, a regularisation/subtraction prescription has been proposed that allows to apply this formalism to calculate next-to-leading order corrections in a consistent way. We illustrate this procedure with the computation of the gluon Regge trajectory at two loops.

  2. Effect and mode of action of some systemic nematicides

    NARCIS (Netherlands)

    Bunt, J.A.

    1975-01-01

    In this study, nematicidal effects, mode of action and specific characters of some systemic nematicides were studied, in search of substitutes for the widely used soil fumigants that require high dosages. The thesis comprises:- a review of literature,- development of techniques,- a test for nematici

  3. Constraining the effective action by a method of external sources

    CERN Document Server

    Garbrecht, Bjorn

    2015-01-01

    We propose a novel method of evaluating the effective action, wherein the physical one- and two-point functions are obtained in the limit of non-vanishing external sources. We illustrate the self-consistency of this method by recovering the usual 2PI effective action due to Cornwall, Jackiw and Tomboulis, differing only by the fact that the saddle-point evaluation of the path integral is performed along the extremal quantum, rather than classical, path. As such, this approach is of particular relevance to situations where the dominant quantum and classical paths are non-perturbatively far away from one-another. A pertinent example is the decay of false vacua in radiatively-generated potentials, as may occur for the electroweak vacuum of the Standard Model. In addition, we describe how the external sources may instead be chosen so as to yield the two-particle-point-irreducible (2PPI) effective action of Coppens and Verschelde. Finally, in the spirit of the symmetry-improved effective action of Pilaftsis and Te...

  4. BEPS Action 2: Neutralizing the Effects on Hybrid Mismatch Arrangements

    NARCIS (Netherlands)

    de Boer, R.; Marres, O.

    2015-01-01

    Curbing tax arbitrage is one of the main priorities of the Organization for Economic Cooperation and Development (OECD) (endorsed by the G20 and the G8) ever since the public debate on base erosion fully erupted. Neutralizing the effect of hybrid mismatch arrangements has become Action No. 2 of the

  5. Effective action approach to dynamical generation of fermion mixing

    CERN Document Server

    Blasone, Massimo; Smaldone, Luca

    2016-01-01

    In this paper we discuss a mechanism for the dynamical generation of flavor mixing, in the framework of the Nambu--Jona Lasinio model. Our approach is illustrated both with the conventional operatorial formalism and with functional integral and ensuing one-loop effective action. The results obtained are briefly discussed.

  6. BEPS Action 2: Neutralizing the Effects on Hybrid Mismatch Arrangements

    NARCIS (Netherlands)

    de Boer, R.; Marres, O.

    2015-01-01

    Curbing tax arbitrage is one of the main priorities of the Organization for Economic Cooperation and Development (OECD) (endorsed by the G20 and the G8) ever since the public debate on base erosion fully erupted. Neutralizing the effect of hybrid mismatch arrangements has become Action No. 2 of the

  7. Effective action for a quantum scalar field in warped spaces

    Energy Technology Data Exchange (ETDEWEB)

    Hoff da Silva, J.M.; Mendonca, E.L.; Scatena, E. [Universidade Estadual Paulista ' ' Julio de Mesquita Filho' ' -UNESP, Departamento de Fisica e Quimica, Guaratingueta, SP (Brazil)

    2015-11-15

    We investigate the one-loop corrections, at zero as well as finite temperature, of a scalar field taking place in a braneworld motivated warped background. After to reach a well-defined problem, we calculate the effective action with the corresponding quantum corrections to each case. (orig.)

  8. Dietary and pharmacological intervention to mitigate the cardiopulmonary effects of air pollution toxicity.

    Science.gov (United States)

    Tong, Haiyan

    2016-12-01

    Exposure to air pollution contributes importantly to excess morbidity and mortality. And while regulatory actions under the "Clean Air Act" have saved millions of lives by improving air quality, there are still millions of people in the U.S. who live in areas where particulate air pollution (PM) levels exceed the U.S. Environmental Protection Agency's National Ambient Air Quality Standards. Therefore, apart from such localities working to attain such standards the protection of the health of public and in particular those at high risk might benefit from interventional strategies that would ameliorate air pollution's adverse health effects. Because inflammation and oxidative stress appear to mediate the health effects of air pollution, one interventional approach to consider is the use of dietary supplementation or medication with anti-inflammatory or antioxidant properties to block the biological responses that initiate the pathophysiological process that culminates in adverse health effects. This article reviews the capability of dietary supplementation, such as antioxidant vitamins, polyunsaturated fatty acids, and medications as a strategy to mitigate air pollution-induced subclinical cardiopulmonary effects. Antioxidant vitamins C and E protect the lungs against short-term ozone and PM exposure. Polyunsaturated fatty acids, such as fish oil and olive oil appear to offer protection against short-term air pollution-induced adverse cardiovascular responses. Taking dietary supplements or medications with antioxidant or anti-inflammatory properties has the potential to provide at least partial protection against air pollution-induced adverse health effects in those individuals who are known to be most susceptible, namely those with pre-existing respiratory and cardiovascular diseases. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Copyright © 2016. Published by Elsevier B.V.

  9. The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3 in Huntington's Disease Mice.

    Directory of Open Access Journals (Sweden)

    Haiqun Jia

    Full Text Available An important epigenetic modification in Huntington's disease (HD research is histone acetylation, which is regulated by histone acetyltransferase and histone deacetylase (HDAC enzymes. HDAC inhibitors have proven effective in HD model systems, and recent work is now focused on functional dissection of the individual HDAC enzymes in these effects. Histone deacetylase 3 (HDAC3, a member of the class I subfamily of HDACs, has previously been implicated in neuronal toxicity and huntingtin-induced cell death. Hence, we tested the effects of RGFP966 ((E-N-(2-amino-4-fluorophenyl-3-(1-cinnamyl-1H-pyrazol-4-ylacrylamide, a benzamide-type HDAC inhibitor that selectively targets HDAC3, in the N171-82Q transgenic mouse model of HD. We found that RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume. In light of previous studies implicating HDAC3 in immune function, we measured gene expression changes for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays. RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene expression patterns, but did significantly alter the striatal expression of macrophage migration inhibitory factor (Mif, a hormone immune modulator associated with glial cell activation, in N171-82Q transgenic mice, but not WT mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic protein (GFAP immunoreactivity, a marker of astrocyte activation, in the striatum of N171-82Q transgenic mice compared to vehicle-treated mice. These findings suggest that the beneficial actions of HDAC3 inhibition could be related, in part, with lowered Mif levels and its associated downstream effects.

  10. Pharmacological analysis of the effects of benzodiazepines on punished schedule-induced polydipsia in rats.

    Science.gov (United States)

    Pellón, Ricardo; Ruíz, Ana; Lamas, Esmeralda; Rodríguez, Cilia

    2007-02-01

    Food-deprived Wistar rats were exposed to a fixed-time 60-s food delivery schedule until they developed schedule-induced polydipsia. Every fifth lick was then followed by an electric shock during two, signalled, 5-min periods, which ran concurrently with the food delivery schedule. Shock intensities were adjusted to reduce licking to 60-70% of the unpunished licking rates. The benzodiazepine full agonists, diazepam (0.3-3.0 mg/kg), chlordiazepoxide (0.3-10.0 mg/kg), oxazepam (0.3-3.0 mg/kg) and the benzodiazepine partial agonist, RU-32698 (3.0-17.0 mg/kg), led to increases in punished responding at intermediate doses and decreases at the highest doses tested. All benzodiazepine agonists brought about dose-dependent decreases in unpunished schedule-induced polydipsia, with doses required to reduce drinking proving higher than doses required to increase punished schedule-induced polydipsia. The antipunishment effect of 0.3 mg/kg of diazepam was dose-dependently antagonized by flumazenil and the benzodiazepine inverse agonist, RU-34000. Flumazenil effects, however, could reflect actions of flumazenil as a partial inverse agonist at GABAA receptors. RU-32698 at 10.0 mg/kg further facilitated the rate-increasing effect of 0.3 mg/kg of diazepam, but at 17.0 mg/kg partially blocked such antipunishment effect. Overall, the present results extend the similarities of the effects of benzodiazepine compounds on adjunctive and operant patterns of behaviour by showing similar interactions within the benzodiazepine receptor complex.

  11. Review on pharmacological action of lumbricus to treat rheumatism%地龙治疗风湿病的药理作用研究综述

    Institute of Scientific and Technical Information of China (English)

    杨茜茜; 龚国清

    2015-01-01

    本文分析了地龙在药理方面的实验研究结果,并结合相关方面知识从中医、西医两个方面证明了地龙可以治疗风湿病的药理学成因,并且简要介绍了地龙对于治疗各种类型风湿病的临床应用与生化指标,进一步证实了地龙对于治疗风湿病的重要作用。%This paper analyzes the earthworm in the pharmacological aspects of animal experimental results, indirect from the two aspects of traditional Chinese medicine and Western medicine proved earthworm can treat rheumatism causes of pharmacology, and briefly introduces the earthworm for the treatment of various types of rheumatism clinical and biochemical indicators, which further confirmed the earthworm plays an important role in the treatment of rheumatism.

  12. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    Science.gov (United States)

    Liu, Wei

    with translational potential for PVL, which is the primary injury underlying cerebral palsy. After confirming the neuroprotective effects of EPO and CEPO on PVL mice, we continued to study the mechanisms relating to their functions. As we learned from our lab's previous study, microglia play an important role in the pathogenesis of PVL, linking multiple effectors downstream of hypoxia-ischemia and inflammation. We found that EPO and CEPO inhibit microglial activation and reduced the severity of injury. Furthermore, we found that EPO and CEPO decreased the activity of poly (ADP-ribose) polymerase-1 (PARP-1) in activated microglia. PARP-1 activity increases in response to many insults, such as infection, ischemia and toxicity. Therefore, we hypothesized that EPO and CEPO decrease microglial activation by inhibiting PARP-1 activity, and thus leading to protection against inflammation and cell death. Besides pharmacological studies of EPO and CEPO on PVL, we also investigated other endogenous factors that may affect neonatal white matter injury. Heat shock proteins (HSPs) are important chaperones that facilitate appropriate protein folding and modification. HSP60, a chaperonin located in the mitochondria, is one of these important molecules that promote appropriate protein folding. HSP60 expression levels increased significantly in the brains of PVL mice compared with control animals. In microglial cell culture, we found that after LPS treatment, HSP60 expression levels increased both inside microglial cells and in the extracellular medium. In addition, we noted enhanced HSP60 immunoreactivity in the brains of PVL mice, which localized inside activated microglial cells and extracellularly. The rise in HSP60 activity after hypoxia-ischemia and LPS administration implies that it potentially functions as one of the triggers of microglial activation and central nervous system inflammation.

  13. Assessment of the pharmacological effects of alprazolam on electroencephalography using connectivity indexes not affected by volume conduction

    Directory of Open Access Journals (Sweden)

    Joan Francesc Alonso

    2015-04-01

    The fact that the considered indexes were not able to find significant differences in the beta band might indicate that phase-coupling changes induced by the drug are weak or too subtle to be detected, given that all measures are corrected by a baseline recording. This might discourage their use in psychopharmacological studies when assessing low doses, mild effects, or when working with a reduced number of participants. However, correlations with plasma concentrations remained high, indicating that PLI, WPLI and IC should not be totally discarded as means of evaluating pharmacological effects on the brain via EEG recordings.

  14. [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.

  15. CFTR pharmacology.

    Science.gov (United States)

    Zegarra-Moran, Olga; Galietta, Luis J V

    2017-01-01

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

  16. Pharmacological effect of gelsemine on anxiety-like behavior in rat.

    Science.gov (United States)

    Meyer, Laurence; Boujedaini, Naoual; Patte-Mensah, Christine; Mensah-Nyagan, Ayikoe G

    2013-09-15

    The chemical compound gelsemine is the major active principle of the yellow jasmine (Gelsemium) that is generally claimed as possessing anxiolytic properties based on empirical and indirect knowledge. Surprisingly, gelsemine effect on anxiety has until now received only little attention. Here, we used the well-validated method for anxiety assessment, the elevated plus-maze combined with video-tracking, to measure gelsemine action on rat anxiety-like behavior. Rats were intraperitoneally injected (500μl/daily/7days) with gelsemine (10(-6), 10(-10) or 10(-14)M) or control solution. Diazepam (DZP) was used as positive standard anxiolytic and additional controls were naive rats similarly manipulated except being injected. Gelsemine or diazepam treatment did not affect the number of closed arm entries and rears illustrating the rat general activity. In contrast, gelsemine (10(-6) to 10(-10)M) or DZP increased dose-dependently the number of entries and the percent of time spent in the open arms indicating that gelsemine is an anxiolytic. Consistently, we observed that gelsemine (10(-6) to 10(-10)M) or DZP also decreased dose-dependently the percent of protected stretched attend postures, an ethological index of anxiety-like state. Altogether, our results constitute a solid set of fundamental data directly demonstrating anxiolytic properties of gelsemine. The report also opens new perspectives for the development of safe and effective gelsemine- or Gelsemium-based strategies against pathological anxiety.

  17. Effective QED Actions Representations, Gauge Invariance, Anomalies and Mass Expansions

    CERN Document Server

    Deser, Stanley D; Seminara, D

    1998-01-01

    We analyze and give explicit representations for the effective abelian vector gauge field actions generated by charged fermions with particular attention to the thermal regime in odd dimensions, where spectral asymmetry can be present. We show, through $\\zeta-$function regularization, that both small and large gauge invariances are preserved at any temperature and for any number of fermions at the usual price of anomalies: helicity/parity invariance will be lost in even/odd dimensions, and in the latter even at zero mass. Gauge invariance dictates a very general ``Fourier'' representation of the action in terms of the holonomies that carry the novel, large gauge invariant, information. We show that large (unlike small) transformations and hence their Ward identities, are not perturbative order-preserving, and clarify the role of (properly redefined) Chern-Simons terms in this context. From a powerful representation of the action in terms of massless heat kernels, we are able to obtain rigorous gauge invariant...

  18. Action co-representation: the joint SNARC effect.

    Science.gov (United States)

    Atmaca, Silke; Sebanz, Natalie; Prinz, Wolfgang; Knoblich, Günther

    2008-01-01

    Traditionally, communication has been defined as the intentional exchange of symbolic information between individuals. In contrast, the mirror system provides a basis for nonsymbolic and nonintentional information exchange between individuals. We believe that understanding the role of the mirror system in joint action has the potential to serve as a bridge between these two domains. The present study investigates one crucial component of joint action: the ability to represent others' potential actions in the same way as one's own in the absence of perceptual evidence. In two experiments a joint spatial numerical association of response codes (SNARC) effect is demonstrated, providing further evidence that individuals form functionally equivalent representations of their own and others' potential actions. It is shown that numerical (symbolic) stimuli that are mapped onto a spatially arranged internal representation (a mental number line) can activate a co-represented action in the same way as spatial stimuli. This generalizes previous results on co-representation.We discuss the role of the mirror system in co-representation as a basis for shared intentionality and communication.

  19. Action video game training reduces the Simon Effect.

    Science.gov (United States)

    Hutchinson, Claire V; Barrett, Doug J K; Nitka, Aleksander; Raynes, Kerry

    2016-04-01

    A number of studies have shown that training on action video games improves various aspects of visual cognition including selective attention and inhibitory control. Here, we demonstrate that action video game play can also reduce the Simon Effect, and, hence, may have the potential to improve response selection during the planning and execution of goal-directed action. Non-game-players were randomly assigned to one of four groups; two trained on a first-person-shooter game (Call of Duty) on either Microsoft Xbox or Nintendo DS, one trained on a visual training game for Nintendo DS, and a control group who received no training. Response times were used to contrast performance before and after training on a behavioral assay designed to manipulate stimulus-response compatibility (the Simon Task). The results revealed significantly faster response times and a reduced cost of stimulus-response incompatibility in the groups trained on the first-person-shooter game. No benefit of training was observed in the control group or the group trained on the visual training game. These findings are consistent with previous evidence that action game play elicits plastic changes in the neural circuits that serve attentional control, and suggest training may facilitate goal-directed action by improving players' ability to resolve conflict during response selection and execution.

  20. Computing the effective action with the functional renormalization group

    Energy Technology Data Exchange (ETDEWEB)

    Codello, Alessandro [CP3-Origins and the Danish IAS University of Southern Denmark, Odense (Denmark); Percacci, Roberto [SISSA, Trieste (Italy); INFN, Sezione di Trieste, Trieste (Italy); Rachwal, Leslaw [Fudan University, Department of Physics, Center for Field Theory and Particle Physics, Shanghai (China); Tonero, Alberto [ICTP-SAIFR and IFT, Sao Paulo (Brazil)

    2016-04-15

    The ''exact'' or ''functional'' renormalization group equation describes the renormalization group flow of the effective average action Γ{sub k}. The ordinary effective action Γ{sub 0} can be obtained by integrating the flow equation from an ultraviolet scale k = Λ down to k = 0. We give several examples of such calculations at one-loop, both in renormalizable and in effective field theories. We reproduce the four-point scattering amplitude in the case of a real scalar field theory with quartic potential and in the case of the pion chiral Lagrangian. In the case of gauge theories, we reproduce the vacuum polarization of QED and of Yang-Mills theory. We also compute the two-point functions for scalars and gravitons in the effective field theory of scalar fields minimally coupled to gravity. (orig.)

  1. Norm theory and the action-effect: The role of social norms in regret following action and inaction

    NARCIS (Netherlands)

    Feldman, Gilad; Albarracín, Dolores

    2016-01-01

    The action-effect (Kahneman & Tversky, 1982) is one of the most widely cited and replicated effects in the regret literature, showing that negative outcomes are regretted more when they are a result of action compared to inaction. Building on theoretical arguments by norm theory (Kahneman & Miller,

  2. Pharmacological activities of Curcuma caesia

    Directory of Open Access Journals (Sweden)

    Satyendra Singh Baghel

    2013-01-01

    Full Text Available Curcuma caesia Roxb. is a perennial, erect rhizomatous herb with large leaves. Fresh rhizomes are aromatic with intense camphoraceous odour, cultivated for its rhizomes, which are used in traditional medicine. The plant is reported to contain camphor, ar-turmerone, (Z-ocimene, ar-curcumene, 1, 8-cineole, elemene, borneol, bornyl acetate and curcumene as the major constituents. The plant has been reported to have antifungal activity, anti-asthmatic, smooth muscle relaxant, antimicrobial activity, antioxidant activity, analgesic, locomotor depressant, anticonvulsant and muscle relaxant effects, anti-inflammatory properties. It is now considered as a valuable source of unique natural products for development of medicines against various diseases. This review gives a view mainly on the meditional uses, phytochemistry and pharmacological actions of the plant.

  3. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action.

    Science.gov (United States)

    Poudyal, Hemant; Panchal, Sunil K; Diwan, Vishal; Brown, Lindsay

    2011-10-01

    Epidemiological, human, animal, and cell culture studies show that n-3 fatty acids, especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n-3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n-3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n-3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n-3 and n-6 fatty acids as well as the interactions of n-3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n-3 fatty acids to reduce the risk factors of metabolic syndrome.

  4. 牛蒡的药理作用研究进展%Advances in Pharmacological Effects of Arctium Lappa L.

    Institute of Scientific and Technical Information of China (English)

    曹旭; 曹剑锋; 陈靠山

    2012-01-01

    OBJECTIVE To introduce advances in the pharmacological effects of Arctium lappa L., and to provide scientific basis for the further utilization. METHODS Consulted domestic and foreign literatures in recent 20 years and provided an overview of the pharmacological effects of burdock. RESULTS The advances in pharmacological effects such as antitumor, anti-inflammatory, immune modulation, antimicrobial, antiviral, antidiabetic, antioxidant, hepatoprotective effect, anti-fatigue, lipid-lowering and treatment erectile dysfunction of Arctium lappa L. Were given. It was universally studied that Arctium lappa L. Possess effects of immune regulation, anti-cancer and treatment diabetes with the potential development value. The research on the efficacy of burdock to treat erectile dysfunction in our laboratory provided a new direction for burdock development and utilization. CONCLUSION It's found that the pharmacological effects of burdock have great development value, especially in the treatment of chronic diseases.%目的 介绍牛蒡的药理作用研究进展,为进一步利用牛蒡提供依据.方法 通过查阅近20年的国内外文献,对牛蒡的药理作用进行概述.结果 牛蒡具有抗肿瘤、抗炎及免疫调节、抗菌、抗病毒、抗糖尿病、抗氧化、肝保护作用、抗疲劳、降血脂、治疗勃起功能障碍及其他多种药理作用,其中对牛蒡的免疫调节、抗癌作用及其治疗糖尿病的作用研究较多,具有潜在的开发应用价值.笔者所在实验室关于牛蒡治疗勃起功能障碍作用的研究为牛蒡开发利用提供了新的方向.结论 牛蒡具有较大的开发利用价值,特别是在治疗慢性疾病方面.

  5. Effectiveness of modified seminars as a teaching-learning method in pharmacology

    Science.gov (United States)

    Palappallil, Dhanya Sasidharan; Sushama, Jitha; Ramnath, Sai Nathan

    2016-01-01

    Context: Student-led seminars (SLS) are adopted as a teaching-learning (T-L) method in pharmacology. Previous studies assessing the feedback on T-L methods in pharmacology points out that the traditional seminars consistently received poor feedbacks as they were not favorite among the students. Aims: This study aimed to obtain feedback on traditional SLS, introduce modified SLS and compare the modified seminars with the traditional ones. Settings and Design: This was a prospective interventional study done for 2 months in medical undergraduates of fifth semester attending Pharmacology seminars at a Government Medical College in South India. Subjects and Methods: Structured questionnaire was used to elicit feedback from participants. The responses were coded on 5-point Likert scale. Modifications in seminar sessions such as role plays, quiz, tests, group discussion, and patient-oriented problem-solving exercises were introduced along with SLS. Statistical Analysis Used: The data were analyzed using SPSS version 16. The descriptive data were expressed using frequencies and percentages. Wilcoxon signed rank test, and Friedman tests were used to compare traditional with modified seminars. Results: The participants identified interaction as the most important component of a seminar. Majority opined that the teacher should summarize at the end of SLS. Student feedback shows that modified seminars created more interest, enthusiasm, and inspiration to learn the topic when compared to traditional SLS. They also increased peer coordination and group dynamics. Students opined that communication skills and teacher-student interactions were not improved with modified seminars. Conclusions: Interventions in the form of modified SLS may be adopted to break the monotony of traditional seminars through active participation, peer interaction, and teamwork. PMID:27563587

  6. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was perfo...... recovery of human skeletal muscle.......The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  7. Covariant effective action for a Galilean invariant quantum Hall system

    Science.gov (United States)

    Geracie, Michael; Prabhu, Kartik; Roberts, Matthew M.

    2016-09-01

    We construct effective field theories for gapped quantum Hall systems coupled to background geometries with local Galilean invariance i.e. Bargmann spacetimes. Along with an electromagnetic field, these backgrounds include the effects of curved Galilean spacetimes, including torsion and a gravitational field, allowing us to study charge, energy, stress and mass currents within a unified framework. A shift symmetry specific to single constituent theories constraints the effective action to couple to an effective background gauge field and spin connection that is solved for by a self-consistent equation, providing a manifestly covariant extension of Hoyos and Son's improvement terms to arbitrary order in m.

  8. Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

    Energy Technology Data Exchange (ETDEWEB)

    Schoepp, D.D.; Ornstein, P.L.; Leander, J.D.; Lodge, D.; Salhoff, C.R.; Zeman, S.; Zimmerman, D.M. (Eli Lilly and Company, Indianapolis, IN (USA))

    1990-12-01

    This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 (cis-(+-)-4-((2H-tetrazol-5-yl)methyl)piperidine-2-carboxylic acid), the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of (3H) CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in (3H)alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or (3H)kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity.

  9. 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.

  10. Pharmacological antagonism of the actions of group II and III mGluR agonists in the lateral perforant path of rat hippocampal slices.

    Science.gov (United States)

    Bushell, T J; Jane, D E; Tse, H W; Watkins, J C; Garthwaite, J; Collingridge, G L

    1996-04-01

    1. An understanding of the physiological and pathological roles of metabotropic glutamate receptors (mGluRs) is currently hampered by the lack of selective antagonists. Standard extracellular recording techniques were used to investigate the activity of recently reported mGluR antagonists on agonist-induced depressions of synaptic transmission in the lateral perforant path of hippocampal slices obtained from 12-16 day-old rats. 2. The group III specific mGluR agonist, (S)-2-amino-4-phosphonobutanoate (L-AP4) depressed basal synaptic transmission in a reversible and dose-dependent manner. The mean (+/-s.e. mean) depression obtained with 100 microM L-AP4 (the maximum concentration tested) was 74 +/- 3% and the IC50 value was 3 +/- 1 microM (n = 5). 3. The selective group II mGluR agonists, (1S,3S)-1-aminocyclopentane-1, 3-dicarboxylate ((1S,3s)-ACPD) and (2S, 1'R, 2'R, 3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) also depressed basal synaptic transmission in a reversible and dose-dependent manner. The mean depression obtained with 200 microM (1S,3S)-ACPD was 83 +/- 8% and the IC50 value was 12 +/- 3 microM (n = 5). The mean depression obtained with 1 microM DCG-IV was 73 +/- 7% and the IC50 value was 88 +/- 15 nM (n = 4). 4. Synaptic depressions induced by the actions of 20 microM (1S,3S)-ACPD and 10 microM L-AP4 were antagonized by the mGluR antagonists (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), (S)-2-methyl-2-amino-4-phosphonobutanoate (MAP4), (2S,1'S,2'S)-2-methyl-2(2'-carboxycyclopropyl)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG), (RS)-alpha-methyl-4-sulphonophenylglycine (MSPG) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (all tested at 500 microM). 5. (+)-MCPG was a weak antagonist of both L-AP4 and (1S,3S)-ACPD-induced depressions. MCCG was selective towards (1S,3S)-ACPD, but analysis of its effects were complicated by apparent partial agonist activity. MAP4 showed good selectivity for L-AP4-induced effects. 6

  11. The Cost Effectiveness of Psychological and Pharmacological Interventions for Social Anxiety Disorder: A Model-Based Economic Analysis.

    Directory of Open Access Journals (Sweden)

    Ifigeneia Mavranezouli

    Full Text Available Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder.A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion.Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT, phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs.Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately the long

  12. The Cost Effectiveness of Psychological and Pharmacological Interventions for Social Anxiety Disorder: A Model-Based Economic Analysis

    Science.gov (United States)

    Mavranezouli, Ifigeneia; Mayo-Wilson, Evan; Dias, Sofia; Kew, Kayleigh; Clark, David M.; Ades, A. E.; Pilling, Stephen

    2015-01-01

    Background Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder. Methods A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs) of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion. Results Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT), phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs. Conclusion Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately

  13. 76 FR 3912 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... how to optimally utilize mechanistic biomarkers and apply clinical pharmacology tools, such as...

  14. Misunderstanding that the Effective Action is Convex under Broken Symmetry

    CERN Document Server

    Asanuma, Nobu-Hiko

    2016-01-01

    The widespread belief that the effective action is convex and has a flat bottom under broken global symmetry is shown to be wrong. We show spontaneous symmetry breaking necessarily accompanies non-convexity in the effective action for quantum field theory, or in the free energy for statistical mechanics, and clarify the magnitude of non-convexity. For quantum field theory, it is also explicitly proved that translational invariance breaks spontaneously when the system is in the non-convex region, and that different vacua of spontaneously broken symmetry cannot be superposed. As applications of non-convexity, we study the first-order phase transition which happens at the zero field limit of spontaneously broken symmetry, and we propose a simple model of phase coexistence which obeys the Born rule.

  15. Advances in Pharmacological Actions and Mechanisms of Doxycycline in the Inhibition of Matrix Metallo-proteinase%多西环素抑制金属蛋白酶药理作用及机制研究进展

    Institute of Scientific and Technical Information of China (English)

    陈薇; 付翔; 黄鹂莺姿; 毛柳珺; 戴莉琳

    2015-01-01

    Doxycycline is a broad-spectrum antimicrobial agent used in clinical for a long time. In recent years, many studies showed that its pharmacological activities of anti-tumor, heart function improvement, nerve protection and antiasthma depended on its inhibition of matrix metalloproteinase ( MMPs) . In the present paper,the new pharmacological actions of doxycycline were reviewed to promote the applications in clinics.%多西环素作为广谱抗菌药物长期应用于临床,近年来很多研究表明多西环素通过抑制金属蛋白酶( MMPs)而具有抗肿瘤、改善心功能,保护神经,平喘等多种药理活性。本文对多西环素新的药理作用进行综述,从而促进其在临床的广泛应用。

  16. Gauge symmetry breaking in gravity and auxiliary effective action

    Science.gov (United States)

    Akhavan, Amin

    2017-02-01

    In the context of the covariant symmetry breaking in gravity, we study the quantum aspect of Chamseddine-Mukhanov model by making use of path integral method. Utilizing one of the gauge fixing constraints, we remove the specific ghost degree of freedom. In continuation, we define an auxiliary effective action. Introducing an auxiliary field, we will have a new dynamic field in addition to the fundamental field.

  17. Effects of pH and Iminosugar Pharmacological Chaperones on Lysosomal Glycosidase Structure and Stability

    Energy Technology Data Exchange (ETDEWEB)

    Lieberman, Raquel L.; D’aquino, J. Alejandro; Ringe, Dagmar; Petsko, Gregory A.; (Harvard-Med); (Brandeis)

    2009-06-05

    Human lysosomal enzymes acid-{beta}-glucosidase (GCase) and acid-{alpha}-galactosidase ({alpha}-Gal A) hydrolyze the sphingolipids glucosyl- and globotriaosylceramide, respectively, and mutations in these enzymes lead to the lipid metabolism disorders Gaucher and Fabry disease, respectively. We have investigated the structure and stability of GCase and {alpha}-Gal A in a neutral-pH environment reflective of the endoplasmic reticulum and an acidic-pH environment reflective of the lysosome. These details are important for the development of pharmacological chaperone therapy for Gaucher and Fabry disease, in which small molecules bind mutant enzymes in the ER to enable the mutant enzyme to meet quality control requirements for lysosomal trafficking. We report crystal structures of apo GCase at pH 4.5, at pH 5.5, and in complex with the pharmacological chaperone isofagomine (IFG) at pH 7.5. We also present thermostability analysis of GCase at pH 7.4 and 5.2 using differential scanning calorimetry. We compare our results with analogous experiments using {alpha}-Gal A and the chaperone 1-deoxygalactonijirimycin (DGJ), including the first structure of {alpha}-Gal A with DGJ. Both GCase and {alpha}-Gal A are more stable at lysosomal pH with and without their respective iminosugars bound, and notably, the stability of the GCase-IFG complex is pH sensitive. We show that the conformations of the active site loops in GCase are sensitive to ligand binding but not pH, whereas analogous galactose- or DGJ-dependent conformational changes in {alpha}-Gal A are not seen. Thermodynamic parameters obtained from {alpha}-Gal A unfolding indicate two-state, van't Hoff unfolding in the absence of the iminosugar at neutral and lysosomal pH, and non-two-state unfolding in the presence of DGJ. Taken together, these results provide insight into how GCase and {alpha}-Gal A are thermodynamically stabilized by iminosugars and suggest strategies for the development of new pharmacological

  18. 吡咯里西啶生物碱的药理作用、毒性及药(毒)物代谢动力学研究进展%Advance on pharmacologic actions, toxicity and pharmacokinetics of pyrrolizidine alkaloids

    Institute of Scientific and Technical Information of China (English)

    高江国; 王长虹; 李岩; 王峥涛

    2009-01-01

    含有吡咯里西啶生物碱的植物在传统医药中有广泛使用,其肝毒性引起广泛关注.作者综述了吡咯里西啶生物碱的药理作用、毒性和药(毒)物代谢动力学等方面的研究进展,以便为后期研究提供基础.%Plants containing pyrrolizidine alkaloids were widely used in traditional medicine. Its hepatotoxicity is main toxicity as well known internationally.In order to providing some foundation for the future studies, the advancement on the pharmacologic actions,toxicity, and pharmacokinetics or toxicokinetics of pyrrolizidine alkaloids was reviewed.

  19. A review on pharmacological action of active principle in gastrodia elata and the clinical application%天麻有效成分的药理作用与临床应用研究进展

    Institute of Scientific and Technical Information of China (English)

    周慧君

    2016-01-01

    本论文主要通过文献查阅,对天麻的药理作用进行了归纳和整理。天麻在药理上对中枢神经系统有镇静、镇痛、抗惊厥的作用,对心血管系统有降血压、抗血小板聚集作用,还能够改善记忆、延缓衰老、增强免疫力等。%In this article, pharmacological action of active principle in gastrodia elata was generalized through consulting the literatures. The results shows that gastrodia elata on central nervous system play roles of sedation, analgesia and anticonvulsant, and on cardiovascular system play roles of lowering blood pressure, anti-platelet aggregation, and could improve memory, aging, strengthening the immune system and so on.

  20. Topics In Gauge Theory (effective Action, Quantum Electrodynamics, Chern Simons)

    CERN Document Server

    Hall, T M

    1998-01-01

    This dissertation will present studies in three distinct areas of gauge theories. In Chern-Simons theories, the fate of the quantized Chern-Simons coupling constant upon renormalization of the theory is investigated. We find the Chern-Simons coupling constant remains quantized in the presence of residual non-abelian gauge symmetry. A two-flavor model of fermions is studied to determine the extent at which the vacuum condensate is locally proportional to the magnetic field. We find the proportionality is local in the limit of large flux. Using resolvent techniques, we find the exact effective action in a single pulsed electric background gauge field $E\\sb1$(t) = Esech $\\sp2$($t\\over r$). We derive the zero and first order derivative expansion for this electric field and compare with our exact results. Dispersion relations between the real and imaginary parts of the exact effective action are derived. In a uniform semi-classical approximation, we find the exact effective action for a spatially homogeneous backg...

  1. Effects of pharmacological concentrations of dietary zinc oxide on growth of post-weaning pigs: a meta-analysis.

    Science.gov (United States)

    Sales, James

    2013-06-01

    Pharmacological dietary zinc (Zn) concentrations of 1,000 to 3,000 mg/kg diet from Zn oxide have been found to increase growth in post-weaning pigs. However, results were inconsistent among studies. A frequentist meta-analysis, in which effects were numerically described with standardized effect sizes (Hedges's g), was conducted in order to identify and quantify the responses in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G/F) in post-weaning pigs upon dietary Zn supplementation from Zn oxide. The inability of independent continuous variables to explain significant heterogeneity obtained with fixed effect models necessitated the use of random effects models to calculate summary statistics. Dietary Zn supplementation increased (P pigs, and its reduction in diets due to potential environmental pollution will have to be negated by alternative feed additives and management strategies in order to prevent economic losses.

  2. In vivo EPR: an effective new tool for studying pathophysiology, physiology and pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Maeder, K.; Swartz, H.M. [Dartmouth Univ., Hanover, NH (United States). Dept. of Radiology; Gallez, B. [Louvain Univ., Brussels (Belgium). Dept. of Medicinal Chemistry

    1996-11-01

    The development of spectrometers working at lower frequencies with improved resonators now permits the routine use of non-invasive EPR spectroscopy in vivo. The capabilities of EPR spectra to reflect environmental conditions, combined with the use of paramagnetic materials as selective non-toxic labels, has led to increasingly widespread and productive applications of the technique to complex problems involving physiology, pharmacology and pathophysiology. Some of the especially promising applications in which EPR techniques uniquely appear to provide valuable information are illustrated, including the measurement of oxygen and oxygen gradients, monitoring of the metabolism of xenobiotics, monitoring pharmacokinetics of drugs, measurement of perfusion, measurement of pH, recognition and labeling of receptors, and characterization of drug releasing systems. (author).

  3. Pharmacological management of chronic lower back pain: a review of cost effectiveness.

    Science.gov (United States)

    Haas, Marion; De Abreu Lourenco, Richard

    2015-06-01

    Lower back pain is one of the most prevalent musculoskeletal conditions in the developed world and accounts for significant health services use. The American College of Physicians and the American Pain Society have published a joint clinical guideline that recommends providing patients with information on prognosis and self-management, the use of medications with proven benefits and, for those who do not improve, consideration be given to the use of spinal manipulation (for acute lower back pain only), interdisciplinary rehabilitation, exercise, acupuncture, massage, yoga, cognitive behavioural therapy or relaxation. The purpose of this review was to evaluate published economic evaluations of pharmacological management for chronic lower back pain. A total of seven studies were eligible for inclusion in there view. The quality of the economic evaluations undertaken in the included studies was not high. This was primarily because of the nature of the underlying clinical evidence, most of which did not come from rigorous randomised controlled trials (RCTs), and the manner in which it was incorporated into the economic evaluations. All studies provided reasonable information about what aspects of healthcare and other resource use were identified, measured and valued. However, the reporting of total costs was not uniform across studies. Measures of pain and disability were the most commonly collected outcomes measures. Two studies collected information on quality of life directly from participants while two studies modelled this information based on the literature. Future economic evaluations of interventions for chronic lower back pain, including pharmacological interventions, should be based on the results of well-conducted RCTs where the measurement of costs and outcomes such as quality of life and quality-adjusted life-years is included in the trial protocol, and which have a follow-up period sufficient to capture meaningful changes in both costs and outcomes. In

  4. Brane Effective Actions, Kappa-Symmetry and Applications

    Directory of Open Access Journals (Sweden)

    Joan Simón

    2012-02-01

    Full Text Available This is a review on brane effective actions, their symmetries and some of their applications. Its first part covers the Green–Schwarz formulation of single M- and D-brane effective actions focusing on kinematical aspects: the identification of their degrees of freedom, the importance of world volume diffeomorphisms and kappa symmetry to achieve manifest spacetime covariance and supersymmetry, and the explicit construction of such actions in arbitrary on-shell supergravity backgrounds. Its second part deals with applications. First, the use of kappa symmetry to determine supersymmetric world volume solitons. This includes their explicit construction in flat and curved backgrounds, their interpretation as Bogomol’nyi–Prasad–Sommerfield (BPS states carrying (topological charges in the supersymmetry algebra and the connection between supersymmetry and Hamiltonian BPS bounds. When available, I emphasise the use of these solitons as constituents in microscopic models of black holes. Second, the use of probe approximations to infer about the non-trivial dynamics of strongly-coupled gauge theories using the anti de Sitter/conformal field theory (AdS/CFT correspondence. This includes expectation values of Wilson loop operators, spectrum information and the general use of D-brane probes to approximate the dynamics of systems with small number of degrees of freedom interacting with larger systems allowing a dual gravitational description. Its final part briefly discusses effective actions for N D-branes and M2-branes. This includes both Super-Yang-Mills theories, their higher-order corrections and partial results in covariantising these couplings to curved backgrounds, and the more recent supersymmetric Chern–Simons matter theories describing M2-branes using field theory, brane constructions and 3-algebra considerations.

  5. The Effect of Non-Pharmacological Methods of Labor Pain Relief on Mothers’ Perceived Stress: ARandomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Mojghan Mirghafourvand

    2014-12-01

    Full Text Available Background & objectives: Childbirth is the most stressful event for the women both mentally and physically affecting their physiological and psychological indicators during labour. The aim of this study was to assess the effect of non-pharmacological methods of labor pain relief in mothers’ perceived stress conducted in Alavi hospital of Ardabil, 2013.  Methods: In this double blind randomized controlled trial, 320 mothers were allocated into two groups by stratified block randomization . The intervention group (n=158 received continuous support throughout the labour process, positioning and movement, music, aromatherapy, showering andconsumption of a light diet or water.The control group received only a routine care. The perceived stress scale (PSS was employed to collect data in three stages at the beginning of the active phase, before the intervention, six hours after birth and then eight weeks postpartum. The two groupswere compared using General Linear Model with controlling the baseline scores. Results: There were 14 participants loss to follow-up. The mean of perceived stress score in the intervention group was significantly lower than the control group at 6 hours [adjusted mean difference: -1.0 (95% confidence interval: -0.01 to -1.9]. However, there was no difference between two groups in terms of perceived stress score at 8 weeks postpartum (p=0.692.  Conclusion: Non-pharmacological methods of labor pain relief are an effective intervention for reducing perceived stress level in mothers during labor and therefore use of this intervention is recommended.

  6. Research Progress on the Pharmacological Effects of Solanine%龙葵碱药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    曲中原; 邹翔; 邹晓祺; 林淋; 刘影; 张逸乔; 季宇彬

    2014-01-01

    龙葵碱主要存在于茄科植物马铃薯(Solanum tuberosum)的块茎及龙葵(Solanum nigrum)的全草中。近年研究发现,龙葵碱除具有毒性作用外,还具有抗肿瘤、抗病原微生物作用。国内外学者对其药理、毒理作用及机制进行了深入研究。本文对龙葵碱药理学和毒理学研究相关进展进行综述,为其进一步的研究和应用提供参考。%Solanine mainly exist in the tubers of Solanum tuberosum and in the whole herb of Solanum nigrum. In recent years, the studies shows that solanine has anti-tumor and antimicrobial activities except for its toxic effect. Domestic and foreign scholars have con-ducted deep studies on the pharmacological and toxic effects and the mechanisms of solanine. This article reviews the research progress in Pharmacology and toxicology research of solanine, which will provide references for its further research and application.

  7. Using the Psychology of Language to Effectively Communicate Actionable Science

    Science.gov (United States)

    Hall, J. M.

    2014-12-01

    The words used to articulate science can have as significant a psychological impact on public perception as the data itself. It is therefore essential to utilize language that not only accurately relates the scientific information, but also effectively conveys a message that is congruent with the presenter's motivation for expressing the data. This is especially relevant for environmental subjects that are surrounded by emotionally charged, political discourses. For example are terms like catastrophe and disaster; while these words may accurately illustrate impartial scientific data, they will likely trigger psychological responses in audiences such as fear or denial that have a detrimental impact on the human decision making process. I propose a set of 5 key principles to assist in communicating data to the general public that both support the transfer of ideas and the presenter's intended psychological impact. 1) Articulate the underlying intentions that motivate the communication of data in a transparent manner 2) Use language congruent with the presenter's stated intentions 3) Maintain a neutral, non-judgmental attitude towards the complex human psychological and emotional dynamics present in a target audience 4) Demonstrate acceptance and compassion when analyzing past and present human actions that adversely affect the environment 5) Develop a perspective of non-attachment when proposing future actions and/or consequences of current human behaviors. The application of these 5 principles provides a framework to move from our current understanding of problems and solutions to effective physical action that allows us to gracefully adapt with our ever changing planet.

  8. Braneworld effective action An alternative to Kaluza-Klein reduction

    CERN Document Server

    Barvinsky, A O; Rathke, A; Kiefer, C; Barvinsky, Andrei; Kamenshchik, Alexander; Rathke, Andreas; Kiefer, Claus

    2003-01-01

    We construct the braneworld effective action in the two-brane Randall-Sundrum model in a setup alternative to Kaluza-Klein reduction: The action is written as a functional of the two metric and radion fields on the branes. In the low-energy spectrum of the model we find two - one massless and one massive - graviton modes, the mass of the massive mode diverging in the limit of merging branes. Our results confirm a recently proposed model of braneworld inflation with diverging branes. They also suggest the possibility of a new mechanism for a repulsive interbrane potential which can underlie the model of colliding "thick" branes in the Big Crunch/Big Bang transitions in cosmology. Mixing of the obtained massless and massive modes can be interpreted as radion-induced graviton oscillations potentially interesting for gravitational wave astronomy.

  9. Highly Effective Action from Large N Gauge Fields

    CERN Document Server

    Yang, Hyun Seok

    2014-01-01

    Recently John H. Schwarz put forward a conjecture that the world-volume action of a probe $D3$-brane in an AdS5 x S5 background of type IIB superstring theory can be reinterpreted as the highly effective action (HEA) of four-dimensional N=4 superconformal field theory on the Coulomb branch. We argue that the HEA can be derived from the noncommutative (NC) field theory representation of the AdS/CFT correspondence and the Seiberg-Witten (SW) map defining a spacetime field redefinition between ordinary and NC gauge fields. It is based only on the well-known facts that the master fields of large N matrices are higher-dimensional NC U(1) gauge fields and the SW map is a local coordinate transformation eliminating U(1) gauge fields known as the Darboux theorem in symplectic geometry.

  10. Covariant Derivation of Effective Actions for SUSY Topological Defects

    CERN Document Server

    París, J; Roca, Jaume

    1998-01-01

    We make a first step to extend to the supersymmetric arena the effective action method, which is used to covariantly deduce the low energy dynamics of topological defects directly from their parent field theory. By focussing on two-dimensional supersymmetric theories we are able to derive the appropriate change of variables that singles out the low energy degrees of freedom. These correspond to super-worldline embeddings in superspace which are subject to a geometrical constraint. We obtain a supersymmetric and $\\kappa$--invariant low energy expansion, with the standard superparticle action as the leading term, which can be used for the determination of higher-order corrections. Our formulation fits quite naturally with the present geometrical description of also provides a basis for the exploration of these issues in higher-dimensional supersymmetric theories.

  11. Pharmacology and function of melatonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dubocovich, M.L.

    1988-09-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

  12. Gastrointestinal Pharmacology.

    Science.gov (United States)

    Saps, Miguel; Miranda, Adrian

    2017-02-25

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

  13. Side effect of acting on the world: Acquisition of action-outcome statistic relation alters visual interpretation of action outcome

    Directory of Open Access Journals (Sweden)

    Takahiro eKawabe

    2013-09-01

    Full Text Available Humans can acquire the statistical features of the external world and employ them to control behaviors. Some external events occur in harmony with an agent’s action, and thus humans should also be able to acquire the statistical features between an action and its external outcome. We report that the acquired action-outcome statistical features alter the visual appearance of the action outcome. Pressing either of two assigned keys triggered visual motion whose direction was statistically biased either upward or downward, and observers judged the stimulus motion direction. Points of subjective equality (PSE for judging motion direction were shifted repulsively from the mean of the distribution associated with each key. Our Bayesian model accounted for the PSE shifts, indicating the optimal acquisition of the action-effect statistical relation. The PSE shifts were moderately attenuated when the action-outcome contingency was reduced. The Bayesian model again accounted for the attenuated PSE shifts. On the other hand, when the action-outcome contiguity was greatly reduced, the PSE shifts were greatly attenuated, and however, the Bayesian model could not accounted for the shifts. The results indicate that visual appearance can be modified by prediction based on the optimal acquisition of action-effect causal relation.

  14. Predictors of non-pharmacological intervention effect on cognitive function and behavioral and psychological symptoms of older people with dementia.

    Science.gov (United States)

    Hsu, Ting-Jung; Tsai, Hui-Te; Hwang, An-Chun; Chen, Liang-Yu; Chen, Liang-Kung

    2017-04-01

    Our previous work showed that non-pharmacological interventions could effectively reduce the severity of behavioral and psychological symptoms of dementia (BPSD), while the factors influencing the effect of intervention were less explored. Therefore, the main purpose of the present study was to investigate the predictors of the non-pharmacological intervention effect for old veterans with dementia and BPSD. A total of 141 old veterans with dementia living in two veterans' homes in northern Taiwan were recruited. The participants received an organized non-pharmacological intervention program of physical activity/exercise, music therapy, reality orientation, art therapy, reminiscence therapy and horticultural therapy once every week for 6 months. All participants were evaluated by the Barthel Index, Lawton-Brody Instrumental Activities of Daily Living Scale, Mini-Mental State Examination, neuropsychiatric inventory (NPI), and the Cornell Scale for Depression in Dementia before and after the intervention. Logistic regression was used to investigate factors associated with improvement/maintenance of cognition (measured by the Mini-Mental State Examination), and improvement of BPSD (measured by NPI) and its subdomains during the intervention period. Multivariate logistic regression analysis showed that the improvement/maintenance of cognitive function was independently associated with a lower Mini-Mental State Examination score at baseline (odds ratio [OR] 0.88, 95% CI 0.80-0.97, P = 0.008), whereas participants with antipsychotic use were less likely to gain the effect (OR 0.42, 95% CI 0.17-1.04, P = 0.061). In addition, the improvement of BPSD was associated with a higher baseline total NPI score (OR 1.33, 95% CI 1.15-1.55, P effect on reducing overall NPI score, NPI caregiver burden score and NPI subdomains - psychotic, affective and behavior syndrome - in old veterans with dementia. In addition, participants with lower cognitive performance, more severe BPSD

  15. Social pharmacology: expanding horizons.

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

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

  16. Social Pharmacology: Expanding horizons

    Directory of Open Access Journals (Sweden)

    Rituparna Maiti

    2014-01-01

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

  17. Pharmacological management of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, J.R.

    1985-01-01

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

  18. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

    Science.gov (United States)

    Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

    2017-10-01

    Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. PARENTS' AUTHORITY AND THE EFFECTIVENESS OF THEIR EDUCATIONAL ACTIONS

    Directory of Open Access Journals (Sweden)

    Romanowska-Tolloczko Anna

    2010-01-01

    Full Text Available Facing a gradual crisis of moral authority in the modern world, educationalists underline its importance in the education and upbringing process. The first and, for a long period of time, the most important authority for children are their parents, who often fail to understand the nature of their own significance and impact on the child. They often wrongly associate parental authority with unquestionable power and this faulty reasoning carries negative developmental implications as the child's submissiveness is not tantamount to acceptance and may result from his/her weakness or fear rather than from recognizing parental authority. This article is to emphasise that parents need to be fully aware of their own educational actions in the child upbringing process. It is important to understand that such actions affect the way parents are perceived by children. This article suggests a number of behaviours conducive to building and sustaining the sense of authority and respect as these features are fundamental in ensuring the effectiveness of educational actions undertaken by parents in the upbringing process.

  20. Dilaton Effective Action with $\\mathcal{N}=1$ Supersymmetry

    CERN Document Server

    Bobev, Nikolay; Olson, Timothy M

    2013-01-01

    We clarify the structure of the four-dimensional low-energy effective action that encodes the conformal and $U(1)$ R-symmetry anomalies in an $\\mathcal{N}=1$ supersymmetric field theory. The action depends on the dilaton, $\\tau$, associated with broken conformal symmetry, and the Goldstone mode, $\\beta$, of the broken $U(1)$ R-symmetry. We present the action for general curved spacetime and background gauge field up to and including all possible four-derivative terms. The result, constructed from basic principles, extends and clarifies the structure found by Schwimmer and Theisen in arXiv:1011.0696 using superfield methods. We show that the Goldstone mode $\\beta$ does not interfere with the proof of the four-dimensional $a$-theorem based on $2 \\to 2$ dilaton scattering. In fact, supersymmetry Ward identities ensure that a proof of the $a$-theorem can also be based on $2 \\to 2$ Goldstone mode scattering when the low-energy theory preserves $\\mathcal{N}=1$ supersymmetry. We find that even without supersymmetry,...

  1. Effects of policosanol on gastroprotective action of D-002

    Directory of Open Access Journals (Sweden)

    Daisy Carbajal Quintana

    Full Text Available Introduction: policosanol, a mixture of higher aliphatic alcohols purified from sugar cane wax, is used to treat hypercholesterolemia. D-002 (Abexol, a mixture of higher aliphatic alcohols from beeswax, is an antioxidant supplement with gastroprotective effects. Then, concomitant intake of D-002 and policosanol may occur in routine practice, so potential pharmacological interactions between them should be researched on. Objective: to find out the influence of policosanol on the gastroprotective effect of D-002 on the ethanol-induced gastric ulcer model. Methods: rats were randomized into eight groups: one treated with the vehicle (control, two with D-002 (25 and 200 mg/kg, two with policosanol (25 and 200 mg/kg, two with the same doses of D-002 + policosanol and other with sucralfate (100 mg/kg. Treatments were given as single oral doses. One hour after treatment, rats received 60% ethanol orally and one hour later they were killed and their stomachs exposed. Effects on ulcer indexes (UI were assessed. Results: acute oral administration of D-002 (25 and 200 mg/kg significantly reduced the ulcer indexes by 40 % and 68 %, respectively, as compared to the control group, and policosanol by 26 % and 47 %, respectively. The concomitant administration of the same doses of D-002 and policosanol significantly decreased ulcer indexes by 64 % (both given at 25 mg/kg and by 92 % (both given at 200 mg/kg as compared to the respective monotherapies. Sucralfate (100 mg/kg significantly reduced (@ 99 % ulcer indexes compared to the control group. Conclusions: the concomitant oral administration of policosanol with D-00 2 gives greater gastroprotection than D-002 monotherapy, so both products can be taken together.

  2. Pharmacological Evaluation of Total Alkaloids from Nux Vomica: Effect of Reducing Strychnine Contents

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2014-04-01

    Full Text Available The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF. The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP. In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

  3. Effects of gender and cigarette smoking on reactivity to psychological and pharmacological stress provocation.

    Science.gov (United States)

    Back, Sudie E; Waldrop, Angela E; Saladin, Michael E; Yeatts, Sharon D; Simpson, Annie; McRae, Aimee L; Upadhyaya, Himanshu P; Contini Sisson, Regana; Spratt, Eve G; Allen, Julia; Kreek, Mary Jeanne; Brady, Kathleen T

    2008-06-01

    We examined the influence of gender and smoking status on reactivity in two human laboratory stress paradigms. Participants were 46 (21 men, 25 women) healthy individuals who completed the Trier Social Stress Task (i.e., performed speech and math calculations in front of an audience) and a pharmacological stress provocation (i.e., administration of corticotrophin releasing hormone (CRH)) after an overnight hospital stay. Approximately half (53%) of the participants were smokers. Cortisol, adrenocorticotrophin hormone (ACTH), physiologic measures (heart rate, blood pressure), and subjective stress were assessed at baseline and at several time points post-task. Men demonstrated higher baseline ACTH and blood pressure as compared to women; however, ACTH and blood pressure responses were more pronounced in women. Women smokers evidenced a more blunted cortisol response as compared to non-smoking women, whereas smoking status did not affect the cortisol response in men. Finally, there was a more robust cardiovascular and subjective response to the Trier as compared to the CRH. Although preliminary, the findings suggest that women may be more sensitive than men to the impact of cigarette smoking on cortisol response. In addition, there is some evidence for a more robust neuroendocrine and physiologic response to acute laboratory stress in women as compared to men.

  4. Pharmacological evaluation of total alkaloids from nux vomica: effect of reducing strychnine contents.

    Science.gov (United States)

    Chen, Jun; Qu, Yange; Wang, Dongyue; Peng, Pei; Cai, Hao; Gao, Ying; Chen, Zhipeng; Cai, Baochang

    2014-04-10

    The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF) extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF). The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP). In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

  5. Effects of the loss of Atox1 on the cellular pharmacology of cisplatin.

    Science.gov (United States)

    Safaei, Roohangiz; Maktabi, Mohammad H; Blair, Brian G; Larson, Christopher A; Howell, Stephen B

    2009-03-01

    Previous work has demonstrated that the copper (Cu) transporters Ctr1, Atp7a and Atp7b regulate the cellular pharmacology of cisplatin (CDDP) by mediating its uptake and efflux. It was also shown that, in the process of uptake by Ctr1, CDDP triggers the rapid proteasomal degradation of its own transporter. The current study examined the role of the metallochaperone Atox1 in the regulation of uptake, efflux and subcellular distribution of CDDP by using a pair of fibroblast cell lines established from Atox1(+/+) and Atox1(-/-) mice. Atox1 is a metallochaperone that is known to play a central role in distributing Cu within the cells and was recently shown to act as a Cu-dependent transcription factor. Loss of Atox1 increased Cu accumulation and reduced efflux. In contrast, loss of Atox1 reduced the influx of CDDP and subsequent accumulation in vesicular compartments and in DNA. Loss of Atox1 was found to block the CDDP-induced down regulation of Ctr1. Ctr1 was found to be polyubiquitinated in an Atox1-dependent manner during CDDP exposure. In conclusion, Atox1 is required for the polyubiquitination of Ctr1 and the Ctr1-mediated uptake of CDDP.

  6. Advances in studies on chemical constituents and pharmacological effects of Ferula%阿魏化学成分与药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    林君容; 金鸣; 吴春敏

    2014-01-01

    阿魏是我国传统中药材,含有多种活性成分,具有消积,散痞,杀虫的功效,用于肉食积滞,瘀血癥瘕,腹中痞块,虫积腹痛。本文主要从化学成分及药理作用两个方面对国内外有关阿魏的研究进行了总结,以期对阿魏今后的进一步研究提供参考。%As a traditional Chinese herb in our country , Ferula contains a variety of active ingredients with the effect of removing retention ,eliminating mass and destroying parasites ,used for curing meat stagnant ,blood stasis and lump,abdominal mass and abdominal pain by parasites.This paper intended to make a conclusion of the domestic and foreign studies from two aspects of chemical components and pharmacological action on the Ferula ,viewing to provide some reference for the further research on it in future.

  7. Bending effects on lasing action of semiconductor nanowires.

    Science.gov (United States)

    Yang, Weisong; Ma, Yaoguang; Wang, Yipei; Meng, Chao; Wu, Xiaoqin; Ye, Yu; Dai, Lun; Tong, Limin; Liu, Xu; Yang, Qing

    2013-01-28

    High flexibility has been one of advantages for one-dimensional semiconductor nanowires (NWs) in wide application of nanoscale integrated circuits. We investigate the bending effects on lasing action of CdSe NWs. Threshold increases and differential efficiency decreases gradually when we decrease the bending radius step by step. Red shift and mode reduction in the output spectra are also observed. The bending loss of laser oscillation is considerably larger than that of photoluminescence (PL), and both show the exponential relationship with the bending radius. Diameter and mode dependent bending losses are investigated. Furthermore, the polarizations of output can be modulated linearly by bending the NWs into different angles continuously.

  8. Partial Supergravity Breaking and the Effective Action of Consistent Truncations

    CERN Document Server

    Grimm, Thomas W; Lust, Severin

    2014-01-01

    We study vacua of N = 4 half-maximal gauged supergravity in five dimensions and determine crucial properties of the effective theory around the vacuum. The main focus is on configurations with exactly two broken supersymmetries, since they frequently appear in consistent truncations of string theory and supergravity. Evaluating one-loop corrections to the Chern-Simons terms we find necessary conditions to ensure that a consistent truncation also gives rise to a proper effective action of an underlying more fundamental theory. To obtain concrete examples, we determine the N=4 action of M-theory on six-dimensional SU(2)-structure manifolds with background fluxes. Calabi-Yau threefolds with vanishing Euler number are examples of SU(2)-structure manifolds that yield N=2 Minkowski vacua. We find that that one-loop corrections to the Chern-Simons terms vanish trivially and thus do not impose constraints on identifying effective theories. This result is traced back to the absence of isometries on these geometries. E...

  9. The pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine.

    Science.gov (United States)

    Itil, T M; Eralp, E; Ahmed, I; Kunitz, A; Itil, K Z

    1998-01-01

    In 1994, a standardized dry extract of Ginkgo biloba leaves (SeGb), has been approved by German health authorities for the treatment of primary degenerative dementia and vascular dementia. More than 24 different brands of Ginkgo biloba extract are sold in the United States. Tacrine, also known as tetrahydroaminoacrine (THA), and donepezil are currently the only drugs approved in the United States for the treatment of Alzheimer's disease. Previous studies demonstrated that SeGb and tacrine induce significant pharmacological effects on the brains of young, healthy human males, as determined by bioelectrical activity measurements obtained using the quantitative pharmaco-electroencephalogram (QPEEG) method. The type of central nervous system (CNS) effects we have seen on computer-analyzed EEGs (CEEGs) after administration of tacrine or EGb suggests both are "cognitive activators" which are, as a class of products, characterized by a (prepost) relative increase of 7.5 to 13 Hz ("alpha") and decrease of 1.3 to 7.5 Hz ("delta" and "theta") activity. To determine whether EGb or tacrine had noticeable pharmacological effects on elderly subjects diagnosed with possible or probable Alzheimer's, the present open, uncontrolled trial was conducted. Data from 18 subjects (11 males, 7 females) at an average age of 67.4 years with light to moderate dementia (Mini Mental mean score = 23.7, ranges: 15-29 [Geriatric Depression Scale mean scores = 3.7; range: 3.2-5.4]) were analyzed for this presentation. Each subject was randomly administered a single oral "Test-Dose" of either 40 mg of tacrine or 240 mg of EGb2 in two separate sessions within 3- to 7-day intervals. Before drug administration and at 1- and 3-hour intervals after drug administration, CEEGs were recorded for a minimum of 10 minutes. The CEEGs were analyzed using Period Analysis programs we developed for QPEEG. The results indicated that both EGb and, to a lesser degree, tacrine induced pharmacological effects, as

  10. Effective action for the Regge processes in gravity

    Energy Technology Data Exchange (ETDEWEB)

    Lipatov, L.N. [Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg (Russian Federation); Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2011-05-15

    It is shown, that the effective action for the reggeized graviton interactions can be formulated in terms of the reggeon fields A{sup ++} and A{sup --} and the metric tensor g{sub {mu}}{sub {nu}} in such a way, that it is local in the rapidity space and has the property of general covariance. The corresponding effective currents j{sup -} and j{sup +} satisfy the Hamilton-Jacobi equation for a massless particle moving in the gravitational field. These currents are calculated explicitly for the shock wave-like fields and a variation principle for them is formulated. As an application, we reproduce the effective lagrangian for the multi-regge processes in gravity together with the graviton Regge trajectory in the leading logarithmic approximation with taking into account supersymmetric contributions. (orig.)

  11. Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

    Science.gov (United States)

    Inkielewicz-Stepniak, Iwona; Santos-Martinez, Maria Jose; Medina, Carlos; Radomski, Marek W

    2014-01-01

    Background Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells. Methods Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK) was studied using Western blot. Results We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK. Conclusion A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate pharmacological and potentially toxicological effects of AgNPs and F on oral health. PMID:24729703

  12. 黄连素药理作用研究进展%The progress of berberine's pharmacological effects

    Institute of Scientific and Technical Information of China (English)

    左茹; 曹雪滨; 张文生

    2014-01-01

    Berberine,also known as berberine hydrochloride,is extracted from traditional Chinese herb,Coptis chinensis Franch ,which is a natural isoquinoline alkaloid and has extensive pharmacological effects,including anti-inflammatory,anti-cancer,bacteriostat,lipid-lowering,hypoglycemic,etc. Amount of experimental studies and clinical reports found that berberine has therapeutic effects on the diseases of nervous system,endocrine system,digestive system,circulation system,respiratory system,and other sys-tems. This article summarized the pharmacological effects of berberine on various diseases in order to pro-vide references for the treatment of diseases using berberine.%黄连素又称盐酸小檗碱,是从中药黄连中提取的一种天然的异喹啉类生物碱,具有广泛的药理作用,包括抗炎、抗癌、抑菌、降脂、降糖等。实验研究及临床报道发现黄连素对神经系统、内分泌系统、消化系统、循环系统、呼吸系统等多个系统的疾病均具有治疗作用。本文就黄连素对各系统疾病的药理作用进行总结,以期为研究黄连素治疗相关疾病提供借鉴。

  13. Bryostatin-1: pharmacology and therapeutic potential as a CNS drug.

    Science.gov (United States)

    Sun, Miao-Kun; Alkon, Daniel L

    2006-01-01

    Bryostatin-1 is a powerful protein kinase C (PKC) agonist, activating PKC isozymes at nanomolar concentrations. Pharmacological studies of bryostatin-1 have mainly been focused on its action in preventing tumor growth. Emerging evidence suggests, however, that bryostatin-1 exhibits additional important pharmacological activities. In preclinical studies bryostatin-1 has been shown at appropriate doses to have cognitive restorative and antidepressant effects. The underlying pharmacological mechanisms may involve an activation of PKC isozymes, induction of synthesis of proteins required for long-term memory, restoration of stress-evoked inhibition of PKC activity, and reduction of neurotoxic amyloid accumulation and tau protein hyperphosphorylation. The therapeutic potential of bryostatin-1 as a CNS drug should be further explored.

  14. Pharmacologic treatment of sex offenders with paraphilic disorder.

    Science.gov (United States)

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

    2013-05-01

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

  15. Phytochemistry, Pharmacology and Toxicology of Spilanthes acmella: A Review

    Directory of Open Access Journals (Sweden)

    Suchita Dubey

    2013-01-01

    Full Text Available Spilanthes acmella is an important medicinal plant, found in tropical and subtropical countries mainly India and South America. Popularly, it is known as toothache plant which reduces the pain associated with toothaches and can induce saliva secretion. Various extracts and active metabolites from various parts of this plant possess useful pharmacological activities. Literature survey proposed that it has multiple pharmacological actions, which include antifungal, antipyretic, local anaesthetic, bioinsecticide, anticonvulsant, antioxidant, aphrodisiac, analgesic, pancreatic lipase inhibitor, antimicrobial, antinociception, diuretic, vasorelaxant, anti-human immunodeficiency virus, toothache relieve and anti-inflammatory effects. This review is elaborately describing the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. This review would assist researchers to search scientific information in the future.

  16. Phytochemistry, Pharmacology and Toxicology of Spilanthes acmella: A Review

    Science.gov (United States)

    Singh, Mahendra; Saraf, Shubhini A.

    2013-01-01

    Spilanthes acmella is an important medicinal plant, found in tropical and subtropical countries mainly India and South America. Popularly, it is known as toothache plant which reduces the pain associated with toothaches and can induce saliva secretion. Various extracts and active metabolites from various parts of this plant possess useful pharmacological activities. Literature survey proposed that it has multiple pharmacological actions, which include antifungal, antipyretic, local anaesthetic, bioinsecticide, anticonvulsant, antioxidant, aphrodisiac, analgesic, pancreatic lipase inhibitor, antimicrobial, antinociception, diuretic, vasorelaxant, anti-human immunodeficiency virus, toothache relieve and anti-inflammatory effects. This review is elaborately describing the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. This review would assist researchers to search scientific information in the future. PMID:24371437

  17. Phytochemistry, Pharmacology and Toxicology of Spilanthes acmella: A Review.

    Science.gov (United States)

    Dubey, Suchita; Maity, Siddhartha; Singh, Mahendra; Saraf, Shubhini A; Saha, Sudipta

    2013-01-01

    Spilanthes acmella is an important medicinal plant, found in tropical and subtropical countries mainly India and South America. Popularly, it is known as toothache plant which reduces the pain associated with toothaches and can induce saliva secretion. Various extracts and active metabolites from various parts of this plant possess useful pharmacological activities. Literature survey proposed that it has multiple pharmacological actions, which include antifungal, antipyretic, local anaesthetic, bioinsecticide, anticonvulsant, antioxidant, aphrodisiac, analgesic, pancreatic lipase inhibitor, antimicrobial, antinociception, diuretic, vasorelaxant, anti-human immunodeficiency virus, toothache relieve and anti-inflammatory effects. This review is elaborately describing the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. This review would assist researchers to search scientific information in the future.

  18. Effects of pharmacological treatment and photoinactivation on the directional responses of an insect neuron.

    Science.gov (United States)

    Molina, Jorge; Stumpner, Andreas

    2005-12-01

    Soma-ipsilateral branches of the large segmental omega neuron of the phaneropterid bush cricket Ancistrura nigrovittata have smooth endings, which extend through most of the auditory neuropile. Correspondingly, it shows a broad frequency tuning. Large excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) are observed when recording from soma-ipsilateral branches. Stimulation from the soma-ipsilateral side leads to a strong excitation. Soma-contralateral branches have a strong, beaded appearance. IPSPs, which seem to be of soma-contralateral origin, can be recorded from these branches. Stimulation from the soma-contralateral side leads to a strong inhibition of the omega neuron. Soma-contralateral stimulation must be 30-40 dB more intense than soma-ipsilateral stimulation to evoke similar spike numbers in the omega neuron. The side-to-side difference is reduced to 10-15 dB after cutting the input from the soma-contralateral leg (tympanic nerve). The thresholds for eliciting IPSPs by soma-contralateral stimulation correspond roughly to excitatory thresholds of the mirror-image omega with the same stimuli. Pharmacological treatment with picrotoxin (PTX) or photoinactivation of the Lucifer Yellow filled mirror-image omega neuron reduces contralateral inhibition considerably and eliminates all visible IPSPs. Nevertheless, an additional contralateral inhibition survives both procedures and is only eliminated after cutting the soma-contralateral tympanic nerve. These results demonstrate that the mirror-image partners of the omega neuron mutually inhibit each other in bush crickets--as in crickets. This mutual inhibition is PTX-sensitive. At least one additional element exerts contralateral PTX-insensitive inhibition on the omega neuron.

  19. Evaluation of medical and health economic effectiveness of non-pharmacological secondary prevention of coronary heart disease

    Directory of Open Access Journals (Sweden)

    Greiner, Wolfgang

    2009-12-01

    prevention programs shows considerable heterogeneity, there is evidence for the long-term effectiveness concerning mortality, recurrent cardiac events and quality of life. Interventions based on exercise and also multicomponent interventions report more conclusive evidence for reducing mortality, while interventions focusing on psychosocial risk factors seem to be more effective in improving quality of life. Only two studies from Germany fulfill the methodological criteria and are included in this report. Additionally, 25 economic publications met the inclusion criteria. Both, quantity and quality of publications dealing with combined interventions are higher compared with those investigating single component interventions. However, there are difficulties in transferring the international results into the German health care system, because of its specific structure of the rehabilitation system. While international literature mostly shows a positive cost-effectiveness ratio of combined programs, almost without exception, studies investigate out-of hospital or home-based programs. The examination of publications evaluating the cost-effectiveness of single interventions merely shows a positive trend of exercise-based and smoking cessation programs. Due to a lack of appropriate studies, no conclusive evidence regarding psychosocial and dietary interventions is available. Altogether eleven publications concerned with ethical or social issues of non-pharmacological secondary prevention strategies are included. These studies are relatively confirm the assumption that patients with a lower socioeconomic background reflect a population at increased risk and therefore have specific needs to participate in rehabilitation programs. However, there currently remains uncertainty, whether these patients participate in rehabilitation more or less often. As barriers, which deter patients from attending, aspects like a lack of motivation, family commitments or the distance between home and

  20. Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum.

    Science.gov (United States)

    Joseph, R E; Oyler, J M; Wstadik, A T; Ohuoha, C; Cone, E J

    1998-01-01

    This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with

  1. Observation of Simple Intransitive Actions: The Effect of Familiarity

    Science.gov (United States)

    Plata Bello, Julio; Modroño, Cristián; Marcano, Francisco; González–Mora, José Luis

    2013-01-01

    Introduction Humans are more familiar with index – thumb than with any other finger to thumb grasping. The effect of familiarity has been previously tested with complex, specialized and/or transitive movements, but not with simple intransitive ones. The aim of this study is to evaluate brain activity patterns during the observation of simple and intransitive finger movements with differing degrees of familiarity. Methodology A functional Magnetic Resonance Imaging (fMRI) study was performed using a paradigm consisting of the observation of 4 videos showing a finger opposition task between the thumb and the other fingers (index, middle, ring and little) in a repetitive manner with a fixed frequency (1 Hz). This movement is considered as the pantomime of a precision grasping action. Results Significant activity was identified in the bilateral Inferior Parietal Lobule and premotor regions with the selected level of significance (FDR [False Discovery Rate] = 0.01). The extent of the activation in both regions tended to decrease when the finger that performed the action was further from the thumb. More specifically, this effect showed a linear trend (index>middle>ring>little) in the right parietal and premotor regions. Conclusions The observation of less familiar simple intransitive movements produces less activation of parietal and premotor areas than familiar ones. The most important implication of this study is the identification of differences in brain activity during the observation of simple intransitive movements with different degrees of familiarity. PMID:24073213

  2. Constraining gravitational interactions in the M theory effective action

    CERN Document Server

    Basu, Anirban

    2013-01-01

    We consider purely gravitational interactions of the type D^{2k} R^4 in the effective action of M theory in 11 dimensional flat spacetime, where k \\geq 0. The duality between M theory on S^1 and type IIA string theory, and the structure of the dilaton dependence of string amplitudes, show that the only non-vanishing interactions in the M theory effective action have k=3n. The coefficient of the D^{6n} R^4 interaction in M theory is determined by the genus (n+1) string amplitude of the D^{6n} R^4 interaction in the type IIA theory. Focussing on the even-even spin structure part of the type IIA string amplitude, this coefficient is given by the type IIB genus (n+1) amplitude, which we constrain using supersymmetry, S-duality and maximal supergravity. The source terms of the Poisson equations satisfied by the S-duality invariant IIB couplings play a central role in the analysis. This procedure yields partial contributions to several multi-loop type IIB string amplitudes, from which we extract the coefficients of...

  3. 商陆药理作用及毒性研究进展%Review on Pharmacological Effects and Toxicity of Phytolaccae

    Institute of Scientific and Technical Information of China (English)

    李一飞; 姚广涛

    2011-01-01

    This article summarizes its pharmacological effects, toxicity, and adverse reactions, reported in the literatures in recent some 20 years. Modern pharmacological study has proved its multiple function, such as anti-bacteria, anti-inflammatory, anti-virus, anti-tumor, enhancing immunity etc, the main clinical indication includes thrombocytopenic purpura,acute and chronic nephritis,renal edema and psoriasis. Among them,the actions of anti-inflammatory and immunity are prominent. Polysaccharides and saponins could extensively regulate many cytokines.At present, clinical reports on acute poisoning have been found. Patients all show sympathetic nerve excitement and gastrointestinal irritation with different degrees. Toxic performances were related to digestive, central nervous,cardiovascular, respiratory and other systems. Death could be induced as serious toxicity happened. Animal experiments have also confirmed its toxicity, including potential mutagenicity. Therefore, for safety and effectiveness in the clinic, further research and attention should be paid to the adverse responses of Phytolaccae and the approach of decreasing the toxicity.%查阅了近20年有关商陆药理效应,毒性作用及不良反应的报道.药理研究发现具有抗菌、抗炎、抗病毒、抗肿瘤、增强免疫等多重疗效,临床主要用于治疗血小板减少性紫癜、急慢性肾炎、肾水肿、银屑病等病症.其在抗炎和免疫方面的作用尤为突出,多糖和皂苷类成分能够广泛调节多种细胞因子.目前已有关于商陆急性中毒的临床报道,表现为不同程度的交感神经兴奋和胃肠道刺激症状,甚至可能引起死亡.毒性表现涉及消化、中枢神经、心血管、呼吸等多系统;动物实验也证实其毒性,甚至有潜在突变性.为此,在商陆的研究中需要特别关注毒性与减毒的研究,以达到临床使用安全有效的目的.

  4. [Pharmacological treatment of chronic pain].

    Science.gov (United States)

    Willimann, Patrick

    2011-09-01

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

  5. Pharmacologically distinct cardiovascular effects of box jellyfish (Chironex fleckeri) venom and a tentacle-only extract in rats.

    Science.gov (United States)

    Ramasamy, Sharmaine; Isbister, Geoffrey K; Seymour, Jamie E; Hodgson, Wayne C

    2005-02-15

    Using a recently developed technique to extract jellyfish venom from nematocysts, the present study investigated the in vivo cardiovascular effects of Chironex fleckeri venom and tentacle extract (devoid of nematocysts). In anaesthetised rats, venom (10 microg/kg, i.v.) produced a transient pressor response (23+/-4 mmHg) followed, in two of five animals, by cardiovascular collapse. Tentacle extract (100 microg/kg, i.v.) produced a more prolonged hypertensive effect (31+/-3 mmHg) without cardiovascular collapse. Prazosin (50 microg/kg, i.v.) did not have any significant effect on the cardiovascular effects produced by venom. However, prazosin significantly attenuated the pressor response produced by tentacle extract. Ketanserin (1 mg/kg, i.v.) did not have any significant effect on the cardiovascular response of the anaesthetised rat to venom (10 microg/kg, i.v.; 25+/-1 mmHg). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to compare the two jellyfish samples used in the present study. In addition to ensuring reproducibility of future studies and allow comparison with previous research. We show, for the first time, that a pure venom sample extracted from C. fleckeri nematocysts and a tentacle extract have cardiovascular effects in the anaesthetised rat which are different and pharmacologically distinct.

  6. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

    Directory of Open Access Journals (Sweden)

    Lynch Tadhg

    2009-04-01

    Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  7. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

    LENUS (Irish Health Repository)

    Maharaj, Chrisen H

    2009-01-01

    OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  8. Analysis on Pharmacologic Action Features of Active Ingredients of Single Chinese Herbal Medicine for the Treatment of Fatty Liver Based on Literature%基于文献的单味中药有效成分治疗脂肪肝药理作用特点分析

    Institute of Scientific and Technical Information of China (English)

    钟周; 邓焱坤; 胡志希; 许潜; 赖永金; 云波

    2016-01-01

    Objective To analyze pharmacologic action features of single Chinese herbal medicine for the treatment of fatty liver based on literature; To provide references for clinical treatment of fatty liver.Methods Animal research literature about single Chinese herbal medicine for the treatment of fatty liver in CNKI, Wanfang database, and VIP from January 2003 to December 2014 was retrieved by computers. The number of single Chinese herbal medicine and the pharmacologic action features of active ingredients (or extracts) were statistically concluded. Results A total of 279 articles were retrieved, including 67 kinds of single Chinese herbal medicine, among which 8 were used to treat AFLD, 45 were used to treat NAFLD, and 14 were used to treat AFLD and NAFLD simultaneously. Pharmacologic action features of the medicine for AFLD mainly included reducing lipid, protecting liver, antioxidation, and anti-inflammation. Pharmacologic action features of the medicine for NAFLD had the effects of improving insulin resistance additionally.Conclusion Chinese herbal medicine for the treatment of AFLD and NAFLD shows significant efficacy, having the features of multiple pathways and liver damage resistance, which provide references for clinical treatment of fatty liver.%目的:基于文献统计分析单味中药有效成分治疗脂肪肝的药理作用特点,为进一步研究及临床治疗脂肪肝提供参考。方法计算机检索中国知识资源总库(CNKI)、万方数据库、中文科技期刊数据库(VIP)2003年1月-2014年12月报道的单味中药治疗脂肪肝动物研究文献,统计治疗脂肪肝的中药味数,归纳单味中药有效成分(提取成分、水煎剂)的药理作用特点。结果检出符合标准文献279篇,共涉及药物67味,其中用于治疗酒精性脂肪肝(AFLD)的药物8味,治疗非酒精性脂肪肝(NAFLD)的药物45味,同时治疗AFLD及NAFLD的药物14味;治疗AFLD药理作用以调节血

  9. SYNERGIC EFFECT OF THE ACTION OF OPERATIONAL AND FINANCIAL RISK

    Directory of Open Access Journals (Sweden)

    MELANIA ELENA MICULEAC

    2014-10-01

    Full Text Available This paper allows us to understand the complex action of total risk at microeconomic level, taking into account several factors: the area in which it acts: the operating activity, generating an economic risk, and the financing activity, generating a financial risk; the nature of the observed indicators: the nature of the profit and the nature of the cash; the synergic effect of the action of operational and financial risk, resulting the total risk. We consider that the innovative value of the article resides in the suggested model of correlation between the activity volume and the capital structure, because different approaches give different results, that is why we suggest a unitary approach, a more pragmatic one of the phenomenon. Also, we established the phases observed in order to establish the global profitability threshold of an international corporation which develops activities in several sectors, through several branches. In this article we have used the method of real leverage which measures the total risk of a company by mixing the operating leverage with the financial leverage.

  10. Dura’s Effect on Securities Class Actions

    Directory of Open Access Journals (Sweden)

    Scotland M. Duncan

    2008-12-01

    Full Text Available On April 19, 2005, the United States Supreme Court rendered a unanimous decision in Dura Pharmaceuticals, Inc. v. Broudo, which had been described as “the most important securities case in a decade.” Simply put, the decision raises the pleading standard for Rule 10b-5 cases asserting fraud-onthe-market; instead of requiring a showing of ex ante losses, such as inflation at the time of purchase, Dura requires a showing of ex post losses, such as market decline resulting from a corrective disclosure. This paper assesses the decision’s practical implications by examining and empirically testing whether the Supreme Court’s enhanced pleading requirements have impacted the frequency and magnitude of post-Reform Act (PSLRA class action securities cases. Specifically, this paper examines Dura’s effect on the filing and settling of cases, as well as on settlement amount. In particular, the results suggest that Dura, ceteris paribus, has had a statistically significant impact on both the filing and settlement of class actions, suggesting a reduction in frivolous litigation.

  11. Overview of safety pharmacology.

    Science.gov (United States)

    Goineau, Sonia; Lemaire, Martine; Froget, Guillaume

    2013-12-02

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

  12. Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone.

    Directory of Open Access Journals (Sweden)

    Khalid S Mohammad

    Full Text Available During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-beta has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-beta signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-beta signaling on bone remain unclear. To examine the role of TGF-beta in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-beta type I receptor (TbetaRI kinase on bone mass, architecture and material properties. Inhibition of TbetaRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TbetaRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TbetaRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TbetaRI inhibitors may be effective in treating conditions of skeletal fragility.

  13. Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings.

    Science.gov (United States)

    Zanda, Mary T; Fadda, Paola; Chiamulera, Cristiano; Fratta, Walter; Fattore, Liana

    2016-09-01

    An increasing number of novel psychoactive substances are currently available and sold as 'legal highs' or 'research chemicals' accompanied by the indication that they are 'not for human consumption'. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a 'safe' drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties. Yet, very recent preclinical data highlighted a stimulatory effect of MXE on dopamine neurotransmission within the mesolimbic pathway. The aim of this review is to provide an updated review of the behavioral and toxicological effects of MXE as well as the latest findings on its pharmacology that might explain sought effects and frequent occurrence of adverse effects. In light of the growing number of intoxications induced by MXE, knowledge of its short-term and long-term effects is urgently needed. However, the hypothetical rapid antidepressant activity of MXE suggested by its chemical analogy with ketamine and supported by recent preclinical findings deserves further investigation.

  14. Modulatory Effects and Action Mechanisms of Tryptanthrin on Murine Myeloid Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    Hoi-Ling Chan; Hon-Yan Yip; Nai-Ki Mak; Kwok-Nam Leung

    2009-01-01

    Leukemia is the disorder of hematopoietic cell development and is characterized by an uncoupling of cell proliferation and differentiation. There is a pressing need for the development of novel tactics for leukemia therapy as conventional treatments often have severe adverse side effects. Tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) is a naturally-occurring, weakly basic alkaloid isolated from the dried roots of medicinal indigo plants (Ban-Lan-Gen). It has been reported to have various biological and pharmacological activities, including anti-microbial, anti-inflammatory, immunomodulatory and anti-tumor effects. However, its modulatory effects and action mechanisms on myeloid cells remain poorly understood. In this study, tryptanthrin was shown to suppress the proliferation of the murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. It also significantly reduced the growth of WEHI-3B JCS cells in vivo in syngeneic BALB/c mice. However, it exhibited no significant direct cytotoxicity on normal murine peritoneal macrophages. Flow cytometric analysis showed an obvious cell cycle arrest of the tryptanthrin-treated WEHI-3B JCS cells at the G0/G1 phase. The expression of cyclin D2,D3, Cdk 2, 4 and 6 genes in WEHI-3B JCS cells was found to be down-regulated at 24 h as measured by RT-PCR. Morphological and functional studies revealed that tryptanthrin could induce differentiation in WEHI-3B JCS cells, as shown by the increases in vacuolation, cellular granularity and NBT-reducing activity in tryptanthrin-treated cells. Collectively, our findings suggest that tryptanthrin might exert its anti-tumor effect on the murine myelomonocytic leukemia WEHI-3B JCS cells by causing cell cycle arrest and by triggering cell differentiation. Cellular & Molecular Immunology. 2009;6(5):335-342.

  15. Theoretical results on the effect of `shortcut' actions in MDPs

    Science.gov (United States)

    McCarthy, Sara M.; Precup, Doina

    2014-04-01

    Temporally extended actions have been used extensively in reinforcement learning in order to speed up the process of learning good behaviours. While such actions are intuitively appealing, very little work has provided a formal analysis of the advantage that can be obtained by using such actions. In this paper, we tackle this problem using the methodology of stochastic processes. We present case studies of Markov decision processes with actions that allow 'shortcuts' between different parts of the environment, and show how such actions affect the travel time between states. Our main finding is that such actions allow for provably quicker travel around the environment, and the benefit increases with the dimensionality of the state space. Hence, extended actions help in efficiently exploring large, high-dimensional domains.

  16. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized,

  17. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized, double

  18. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized, double

  19. Effective Actions of IIB Matrix Model on S^3

    CERN Document Server

    Kaneko, Hiromichi; Matsumoto, Koichiro

    2007-01-01

    S^3 is a simple principle bundle which is locally S^2 \\times S^1. It has been shown that such a space can be constructed in terms of matrix models. It has been also shown that such a space can be realized by a generalized compactification procedure in the S^1 direction. We investigate the effective action of supersymmetric gauge theory on S^3 with an angular momentum cutoff and that of a matrix model compactification. The both cases can be realized in a deformed IIB matrix model with a Myers Term. We find that the highly divergent contributions at the tree and one loop level are sensitive to the uv cutoff. However the two loop level contributions are universal since they are only logarithmically divergent. We expect that the higher loop contributions are insensitive to the uv cutoff since 3d gauge theory is super renormalizable.

  20. Effective action and vacuum expectations in nonlinear $\\sigma$ model

    CERN Document Server

    Fayzullaev, B A

    2015-01-01

    The equations for effective action for nonlinear $\\sigma$ model are derived using DeWitt method in two forms - for generator of vertex parts $\\Gamma$ and for generator of weakly connected parts $W$. Loop-expansion solutions to these equations are found. It is shown that vacuum expectation values for various quantities including divergence of a N\\"{o}ther current, trace of the energy-momentum tensor and so on, can be calculated by this method. Also it is shown that vacuum expectation to the sigma-field is determined by an explicit combination of tree Green function and classical solution. It is shown that the limit when coupling constant tends to zero is singular one.

  1. Effective action in a higher-spin background

    CERN Document Server

    Bekaert, Xavier; Mourad, Jihad

    2010-01-01

    We consider a free massless scalar field coupled to an infinite tower of background higher-spin gauge fields via minimal coupling to the traceless conserved currents. The set of Abelian gauge transformations is deformed to the non-Abelian group of unitary operators acting on the scalar field. The gauge invariant effective action is computed perturbatively in the external fields. The structure of the various (divergent or finite) terms is determined. In particular, the quadratic part of the logarithmically divergent (or of the finite) term is expressed in terms of curvatures and related to conformal higher-spin gravity. The generalized higher-spin Weyl anomalies are also determined. The relation with the theory of interacting higher-spin gauge fields on anti de Sitter spacetime via the holographic correspondence is discussed.

  2. Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model.

    Science.gov (United States)

    Yaacob, Nik Soriani; Yankuzo, Hassan Muhammad; Devaraj, Sutha; Wong, Jimmy Ka Ming; Lai, Choon-Sheen

    2015-01-01

    Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3) using N-methyl-N-Nitrosourea (NMU)-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.

  3. Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model.

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    Full Text Available Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3 using N-methyl-N-Nitrosourea (NMU-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.

  4. Mephedrone: Public health risk, mechanisms of action, and behavioral effects.

    Science.gov (United States)

    Dybdal-Hargreaves, Nicholas F; Holder, Nicholas D; Ottoson, Paige E; Sweeney, Melanie D; Williams, Tyisha

    2013-08-15

    The recent shortage of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) has led to an increased demand for alternative amphetamine-like drugs such as the synthetic cathinone, 4-methylmethcathinone (mephedrone). Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues. Currently, there is little literature investigating the mechanism of action and long-term effects of mephedrone. As such, we reviewed the current understanding of amphetamines, cathinones, and cocaine emphasizing the potentially translational aspects to mephedrone, as well as contrasting with the work that has been done specifically on mephedrone in order to present the current state of understanding of mephedrone in terms of its risks, mechanisms, and behavioral effects. Emerging research suggests that while there are structural and behavioral similarities of mephedrone with amphetamine-like compounds, it appears that serotonergic signaling may mediate more of mephedrone's effects unlike the more dopaminergic dependent effects observed in traditional amphetamine-like compounds. As new designer drugs are produced, current and continuing research on mephedrone and other synthetic cathinones should help inform policymakers' decisions regarding the regulation of novel 'legal highs.'

  5. Recent Pharmacology Studies on the International Space Station

    Science.gov (United States)

    Wotring, Virginia

    2014-01-01

    The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during long-duration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.

  6. In silico methods for drug repurposing and pharmacology.

    Science.gov (United States)

    Hodos, Rachel A; Kidd, Brian A; Shameer, Khader; Readhead, Ben P; Dudley, Joel T

    2016-05-01

    Data in the biological, chemical, and clinical domains are accumulating at ever-increasing rates and have the potential to accelerate and inform drug development in new ways. Challenges and opportunities now lie in developing analytic tools to transform these often complex and heterogeneous data into testable hypotheses and actionable insights. This is the aim of computational pharmacology, which uses in silico techniques to better understand and predict how drugs affect biological systems, which can in turn improve clinical use, avoid unwanted side effects, and guide selection and development of better treatments. One exciting application of computational pharmacology is drug repurposing-finding new uses for existing drugs. Already yielding many promising candidates, this strategy has the potential to improve the efficiency of the drug development process and reach patient populations with previously unmet needs such as those with rare diseases. While current techniques in computational pharmacology and drug repurposing often focus on just a single data modality such as gene expression or drug-target interactions, we argue that methods such as matrix factorization that can integrate data within and across diverse data types have the potential to improve predictive performance and provide a fuller picture of a drug's pharmacological action. WIREs Syst Biol Med 2016, 8:186-210. doi: 10.1002/wsbm.1337 For further resources related to this article, please visit the WIREs website.

  7. Social Pharmacology: Expanding horizons

    Science.gov (United States)

    Maiti, Rituparna; Alloza, José Luis

    2014-01-01

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

  8. Research Progress in Chemical Components,Pharmacological Actions and Toxicity of Diterpene Lactones Isolated from Dioscoreae Bulbifera L.Rhizome%黄药子二萜内酯类成分化学、药理及毒性研究进展

    Institute of Scientific and Technical Information of China (English)

    王君明; 崔大鹏; 崔瑛

    2011-01-01

    Objective;To explore the research progress in chemical components,pharmacological actions and toxicity of diterpene lactones isolated from dioscoreae bulbifera L. Rhizome. Methods;The related information and references were looked through,and further analyzed and reviewed. Results;Up to now,the diterpene lactones isolated from D. Bulbifera rhizome mainly include diosbulbins A-M,8-epidios-bulbin E acetate,etc. Pharmacological references show that such diterpene lactones have effect on antitumor,anti-inflammation,antimicrobial and so on. However,they may induce hepatotoxicity. Conclusion;We should carry out further studies on dosage-effect relationship and mechanisms of the diterpene lactones isolated from D. Bulbifera rhizome, and finally to determine the safe and effective dose ranges so as to ensure the safety and validity in clinic application.%目的:探讨黄药予二萜内酯类成分化学、药理作用及毒性研究进展.方法:查阅国内外相关研究资料并进行汇总、分析、综述.结果:已发现的二萜内酯类成分主要有黄独素A-M、8-表黄独素乙酸酯等;二萜内酯类成分既是黄药子发挥抗肿瘤、抗炎、抗菌等作用的物质基础,也是其诱导肝毒性的毒性成分.结论:建议开展黄药子二萜内酯类成分的量效关系及作用机制研究,建立其安全有效的剂量范围,最终为其安全有效用药提供有意义的参考.

  9. 中药白芍的药理作用和质量控制研究进展%Advances in research on pharmacological actions and quality control of Paeoniae Radix Alba

    Institute of Scientific and Technical Information of China (English)

    李文艳; 黄山君; 王瑞

    2012-01-01

    Paeoniae Radix Alba, the dry root of Rranunculaceae Paeonia lactiflora Pall. ,is one of commonly used Chinese materia medica. Referring to related literature,studies on pharmacological actions,.such as anti-inflammation,immunoregulation, anti-rheumatoid arthritis and endothclial cells protection,and qualitative and quantitative analyses of Paeoniae Radix Alba are summarized in this paper in order to provide reference for further study on Paeoniae Radix Alba and its preparations.%中药白芍来源于毛茛科植物芍药的干燥根,是常用中药材之一.本文经查阅文献,对白芍的抗炎、免疫调节、抗类风湿关节炎和保护内皮细胞等药理作用,及定性、定量分析方法进行综述,以期为更深入研究白芍药材及其制剂提供参考.

  10. 47 CFR 1.102 - Effective dates of actions taken pursuant to delegated authority.

    Science.gov (United States)

    2010-10-01

    ... delegated authority. 1.102 Section 1.102 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL... by the Commission and Pursuant to Delegated Authority; Effective Dates and Finality Dates of Actions § 1.102 Effective dates of actions taken pursuant to delegated authority. (a) Final actions following...

  11. Learning Associations between Action and Perception: Effects of Incompatible Training on Body Part and Spatial Priming

    Science.gov (United States)

    Wiggett, Alison J.; Hudson, Matt; Tipper, Steve P.; Downing, Paul E.

    2011-01-01

    Observation of another person executing an action primes the same action in the observer's motor system. Recent evidence has shown that these priming effects are flexible, where training of new associations, such as making a foot response when viewing a moving hand, can reduce standard action priming effects (Gillmeister, Catmur, Liepelt, Brass,…

  12. 43 CFR 46.115 - Consideration of past actions in the analysis of cumulative effects.

    Science.gov (United States)

    2010-10-01

    ... Environmental Quality § 46.115 Consideration of past actions in the analysis of cumulative effects. When... Memorandum on Consideration of Past Actions in Cumulative Effects Analysis” dated June 24, 2005, or any... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Consideration of past actions in...

  13. The Pharmacological Effects of Morroniside and Loganin Isolated from Liuweidihuang Wan, on MC3T3-E1 Cells

    OpenAIRE

    Xijun Wang; Hui Sun; Ping Wang; Kun Yang; Wei Wang; Manyu Li

    2010-01-01

    Liuweidihuang Wan (LW), initially a well-known formula for curing “wu chi wu ruan”, is commonly used nowadays for clinical treatment of Postmenopausal Osteoporosis (PO), but the identity of the effective substance(s) remains unclear. The present study was designed to evaluate the effects of morroniside and loganin isolated from LW on the proliferation, differentiation and apoptosis of MC3T3-E1 cells, as well as the possible mechanism of action. Morroniside and loganin had no effects on the pr...

  14. Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren Hein; Holbech, J.; Demant, Dyveke T

    2017-01-01

    baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed. Results: Diabetes as etiology...... of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points......, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years. Conclusion: Despite...

  15. Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers

    NARCIS (Netherlands)

    Doorn, M. van; Vogels, J.; Tas, A.; Hoogdalem, E.J. van; Burggraaf, J.; Cohen, A.; Greef, J. van der

    2007-01-01

    Aims: To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the differen

  16. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.

  17. [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.

  18. Mechanism of Action and Pharmacology of Patiromer, a Nonabsorbed Cross-Linked Polymer That Lowers Serum Potassium Concentration in Patients With Hyperkalemia

    Science.gov (United States)

    Harrison, Stephen D.; Cope, M. Jamie; Park, Craig; Lee, Lawrence; Salaymeh, Faleh; Madsen, Deidre; Benton, Wade W.; Berman, Lance; Buysse, Jerry

    2016-01-01

    Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin–angiotensin–aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin–angiotensin–aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance. PMID:26856345

  19. Ecological effects of contaminants and remedial actions in Bear Creek

    Energy Technology Data Exchange (ETDEWEB)

    Southworth, G.R.; Loar, J.M.; Ryon, M.G.; Smith, J.G.; Stewart, A.J. (Oak Ridge National Lab., TN (United States)); Burris, J.A. (C. E. Environmental, Inc., Tallahassee, FL (United States))

    1992-01-01

    Ecological studies of the Bear Creek watershed, which drains the area surrounding several Oak Ridge Y-12 Plant waste disposal facilities, were initiated in May 1984 and are continuing at present. These studies consisted of an initial, detailed characterization of the benthic invertebrate and fish communities in Bear Creek, and they were followed by a presently ongoing monitoring phase that involves reduced sampling intensities. The characterization phase utilized two approaches: (1) instream sampling of benthic invertebrate and fish communities in Bear Creek to identify spatial and temporal patterns in distribution and abundance and (2) laboratory bioassays on water samples from Bear Creek and selected tributaries to identify potential sources of toxicity to biota. The monitoring phase of the ecological program relates to the long-term goals of identifying and prioritizing contaminant sources and assessing the effectiveness of remedial actions. It continues activities of the characterization phase at less frequent intervals. The Bear Greek Valley is a watershed that drains the area surrounding several closed Oak Ridge Y-12 Plant waste disposal facilities. Past waste disposal practices in Bear Creek Valley resulted in contamination of Bear Creek and consequent ecological damage. Extensive remedial actions have been proposed at waste sites, and some of the have been implemented or are now underway. The proposed study plan consists of an initial, detailed characterization of the benthic invertebrate and fish communities in Bear Creek in the first year followed by a reduction in sampling intensity during the monitoring phase of the plan. The results of sampling conducted from May 1984 through early 1989 are presented in this report.

  20. PHARMACOLOGICAL SCREENING OF ISOLATED COMPOUND FROM MADHUKA LONGIFOLIA SEEDS GIVES SIGNIFICANT ANALGESIC EFFECT

    Directory of Open Access Journals (Sweden)

    Chirantan S. Chakma

    2011-08-01

    Full Text Available The study was carried out to assess the analgesic effect of aqueous and ethanolic extracts of isolated compound from M.longifolia seeds in rats and mice model. All three animal groups were administered the aq. and alc.ext of M.longifolia at a dose of 4 mg to 64 mg/kg body weight. The standard drug diclofenac 5 mg/kg b.w is used in three screening method. The paw licking time, tail withdrawal time and chemical writhings in mice both aq. and alc. extracts of M.longifolia prevents significant dose dependent anti-nociceptive effect. Diclofenac 5 mg/kg failed to alter significantly the antinociceptive effect of 16 to 32 mg of both extracts or the effect on chemical assay.

  1. Vascular effects of aqueous extract of Chamaemelum nobile: in vitro pharmacological studies in rats.

    Science.gov (United States)

    Zeggwagh, Naoufel Ali; Michel, Jean Baptiste; Eddouks, Mohamed

    2013-01-01

    This study aims to evaluate the in vitro vasorelaxant effect of C. nobile aqueous extract. We use aortic ring isolated from Wistar rats and aqueous C. nobile extract at doses of 5, 10 and 20 mg/ml. Incubation of aqueous C. nobile extract for 30 minutes produced a significant shift of the dose-response curve to norepinephrine (NE) (10(-8) to 10(-5) M) (p nobile extract possesses in vitro vasorelaxant effect.

  2. Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports.

    Science.gov (United States)

    Ehrnborg, Christer; Rosén, Thord

    2008-05-01

    Growth Hormone (GH) is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombinant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH's rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span (24-36 hours) from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial.However, work with different approaches to develop an alternative, reliable test is ongoing.

  3. Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma.

    Science.gov (United States)

    Zhang, Issan; Cui, Yiming; Amiri, Abdolali; Ding, Yidan; Campbell, Robert E; Maysinger, Dusica

    2016-03-01

    Increased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

  4. Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis

    Directory of Open Access Journals (Sweden)

    J. Ruth Wu-Wong

    2010-01-01

    Full Text Available Vitamin D receptor agonists (VDRAs directly suppress parathyroid hormone (PTH mRNA expression. Different VDRAs are known to have differential effects on serum calcium (Ca, which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the Ca-sensing receptor (CaSR. In this study, we compared the effects of paricalcitol and doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR mRNA. The 5/6 nephrectomized (NX Sprague-Dawley rats on a normal or hyperphosphatemia-inducing diet were treated with vehicle, paricalcitol, or doxercalciferol for two weeks. Both drugs at the tested doses (0.042–0.33 g/kg suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol. In pig parathyroid cells, paricalcitol and the active form of doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH mRNA expression and inhibited cell proliferation in a similar manner, although paricalcitol induced the expression of CaSR mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH mRNA reflect the complex involvement of the vitamin D axis in regulating the mineral homeostasis system.

  5. Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease

    Science.gov (United States)

    Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Álvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

    2012-01-01

    BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. PMID:22747838

  6. Effect of pharmacological interventions on the fronto-cingulo-parietal cognitive control network in psychiatric disorders: a transdiagnostic systematic review of fMRI studies

    Directory of Open Access Journals (Sweden)

    Therese eVan Amelsvoort

    2016-05-01

    Full Text Available Executive function deficits such as working memory, decision-making, and attention problems are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future pro-cognitive pharmacological interventions. 29 manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n=11, depression (n=4, bipolar disorder (n=4, ADHD (n=4, OCD (n=2, smoking dependence (n=2, alcohol dependence (n=1 and pathological gambling (n=1. In terms of impact on the fronto-cingulo-parietal networks, the preliminary evidence for catechol-o-methyl-transferase inhibitors, nicotinic receptor agonists and atomoxetine suggested was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future pro-cognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds.

  7. Effect of Pharmacological Interventions on the Fronto-Cingulo-Parietal Cognitive Control Network in Psychiatric Disorders: A Transdiagnostic Systematic Review of fMRI Studies

    Science.gov (United States)

    van Amelsvoort, Thérèse; Hernaus, Dennis

    2016-01-01

    Executive function deficits, such as working memory, decision-making, and attention problems, are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate) on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future procognitive pharmacological interventions. Twenty-nine manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n = 11), depression (n = 4), bipolar disorder (n = 4), ADHD (n = 4), OCD (n = 2), smoking dependence (n = 2), alcohol dependence (n = 1), and pathological gambling (n = 1). In terms of impact on the fronto-cingulo-parietal network, the preliminary evidence for catechol-O-methyl-transferase inhibitors, nicotinic receptor agonists, and atomoxetine was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future procognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds. PMID:27242552

  8. A Review of the Pharmacological Effects of the Dried Root of Polygonum cuspidatum (Hu Zhang and Its Constituents

    Directory of Open Access Journals (Sweden)

    Huan Zhang

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM has been widely used in China for thousands of years to treat and prevent diseases. TCM has been proven safe and effective, and it is being considered as one of the important types of complementary and alternative medicine and receives increasing attention worldwide. The dried root of Polygonum cuspidatum Sieb. et Zucc. (also known as “Hu Zhang” in Chinese is one of the medicinal herbs listed in the Pharmacopoeia of the People's Republic of China. Hu Zhang is widely distributed in the world. It can be found in Asia and North America and is used as folk medicine in countries such as Japan and Korea. In China, Hu Zhang is usually used in combination with other TCM herbs. The therapeutic uses of those Hu Zhang-containing TCM prescriptions or formulations are for treating cough, hepatitis, jaundice, amenorrhea, leucorrhea, arthralgia, burns and snake bites. Recent pharmacological and clinical studies have indicated that Hu Zhang has antiviral, antimicrobial, anti-inflammatory, neuroprotective, and cardioprotective functions. This review gives a summary of the reported therapeutic effects of the active compounds and the different extracts of Hu Zhang.

  9. Flupirtine : Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    S Harish

    2012-01-01

    Full Text Available Flupirtine is neither an opioid nor a non steroidal anti-inflammatory drug (NSAID producing its analgesic action through blockade of glutamate N-methyl-D-aspartate receptor. It is devoid of adverse effects of routinely used analgesic drugs, but is equally efficacious in reducing pain sensation. It has a distinctive mechanism of action, exerting a dual therapeutic effect with both analgesic and muscle relaxant properties that has utility in the treatment of pain, including that associated with muscle tension.

  10. Pharmacology of Casimiroa edulis; Part I. Blood pressure and heart rate effects in the anesthetized rat.

    Science.gov (United States)

    Magos, G A; Vidrio, H

    1991-02-01

    The effect of an alcoholic extract of seeds of Casimiroa edulis on blood pressure and heart rate was determined in rats anesthetized with pentobarbital and compared with that of histamine. The extract induced hypotension, accompanied at high doses by tachycardia. Hypotension after histamine was more transient and was not accompanied by changes in heart rate. Experiments with a variety of autonomic antagonists revealed that extract-induced hypotension was not mediated by histamine H2, muscarinic, or beta-adrenergic receptors, but involved an H1 mechanism. After H1 blockade, the depressor response was reversed to a pressor effect, mediated by alpha-adrenoceptor stimulation. The increase in heart rate was due in part to H1 and in part to beta-adrenergic receptor activation. It was suggested that imidazole derivatives could be responsible for the depressor effect observed. The pressor response could be caused by these or other components of the extract.

  11. Pharmacology of Casimiroa edulis; III. Relaxant and contractile effects in rat aortic rings.

    Science.gov (United States)

    Magos, G A; Vidrio, H; Enríquez, R

    1995-06-23

    The relaxant and contractile effects of an aqueous extract of the seeds of the hypotensive plant Casimiroa edulis were investigated in rat aortic rings. The extract inhibited contractions elicited by noradrenaline, serotonin and prostaglandin F2 alpha, but did not affect responses to KCl. Inhibition did not require the presence of intact vascular endothelium and was not affected by histamine antagonists. In this preparation, the extract also elicited concentration-related contractions which were more marked in the absence of endothelium, were not blocked by histamine antagonists, and were completely suppressed by alpha-adrenergic blockade. It was concluded that the relaxant effect of the extract is not exerted through release of an endothelial relaxing factor nor through blockade of calcium channels or of specific smooth muscle receptors, and does not involve histaminergic mechanisms. The contractile effect is modulated by vascular endothelium and is alpha-adrenergic in nature.

  12. Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder.

    Science.gov (United States)

    Heuzenroeder, Louise; Donnelly, Marie; Haby, Michelle M; Mihalopoulos, Cathrine; Rossell, Ruth; Carter, Rob; Andrews, Gavin; Vos, Theo

    2004-08-01

    To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filter criteria ("equity", "strength of evidence", "feasibility" and "acceptability to stakeholders") is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

  13. Evaluation of pharmacological effect of Teucrium stocksianum extract on angiogenesis using chorioallantoic membrane assay

    Directory of Open Access Journals (Sweden)

    Nazia Tabassum

    2016-09-01

    Full Text Available The present study was aimed to evaluate the effect of Teucrium stocksianum on angiogenesis by using chorioallantoic membrane (CAM assay. Fertilized eggs were incubated on the 5th day and dose of different dilutions 0.03%, 0.05%, 0.1%, and 0.5% of the plant extract was applied on 6th day. Evaluation of primary, secondary and tertiary blood vessels diameter and CAM area on 7th day by SPIP software. T. stocksianum showed antiangiogenic effect by reducing the diameter of CAM of blood vessels by applying the dilutions while significant results were obtained at dilution of 0.5%.

  14. Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical

    OpenAIRE

    Keppel Hesselink JM

    2013-01-01

    Jan M Keppel Hesselink Department of Pharmacology, University of Witten/Herdecke, Witten, Germany Abstract: The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA) and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome prolifera...

  15. Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach.

    Science.gov (United States)

    Orvos, Péter; Virág, László; Tálosi, László; Hajdú, Zsuzsanna; Csupor, Dezső; Jedlinszki, Nikoletta; Szél, Tamás; Varró, András; Hohmann, Judit

    2015-01-01

    Chelidonium majus or greater celandine is spread throughout the world, and it is a very common and frequent component of modern phytotherapy. Although C. majus contains alkaloids with remarkable physiological effect, moreover, safety pharmacology properties of this plant are not widely clarified, medications prepared from this plant are often used internally. In our study the inhibitory effects of C. majus herb extracts and alkaloids on hERG potassium current as well as on cardiac action potential were investigated. Our data show that hydroalcoholic extracts of greater celandine and its alkaloids, especially berberine, chelidonine and sanguinarine have a significant hERG potassium channel blocking effect. These extracts and alkaloids also prolong the cardiac action potential in dog ventricular muscle. Therefore these compounds may consequently delay cardiac repolarization, which may result in the prolongation of the QT interval and increase the risk of potentially fatal ventricular arrhythmias. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module IV. General Pharmacology.

    Science.gov (United States)

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on general pharmacology is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Five units of study are presented: (1) the sources of drugs, drug names, solids and liquids, and the different forms in which drugs may be dispersed; (2) the action (effects) of…

  17. Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications

    DEFF Research Database (Denmark)

    Dzieciuch-Rojek, Monika; Poojari, Chetan; Bednar, Jan

    2017-01-01

    Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore, ...

  18. Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

    Directory of Open Access Journals (Sweden)

    Freek J. Zijlstra

    2003-01-01

    Full Text Available Background: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon.

  19. Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis

    NARCIS (Netherlands)

    F.J. Zijlstra (Freek); M.E. van Meeteren (Marieke); I.M. Garrelds (Ingrid); M.A.C. Meijssen (Maarten)

    2003-01-01

    textabstractBACKGROUND: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth

  20. The pharmacological effect of positive KCNQ (Kv7) modulators on dopamine release from striatal slices

    DEFF Research Database (Denmark)

    Jensen, Majbrit M; Lange, Sofie Cecilie; Thomsen, Morten Skøtt;

    2011-01-01

    Retigabine is an anti-epileptic drug that inhibits neuronal firing by stabilizing the membrane potential through positive modulation of voltage-dependent KCNQ potassium channels in cortical neurons and in mesencephalic dopamine (DA) neurons. The purpose of this study was to compare the effect of ...