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Sample records for action pharmacology effects

  1. Pharmacological action and mechanisms of ginkgolide B

    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.

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

    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. PMID:26644208

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

    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.

  4. Eugenol: a natural compound with versatile pharmacological actions.

    Pramod, Kannissery; Ansari, Shahid H; Ali, Javed

    2010-12-01

    Eugenol, the major constituent of clove oil, has been widely used for its anesthetic and analgesic action in dentistry. Eugenol exhibits pharmacological effects on almost all systems and our aim is to review the research work that has identified these pharmacological actions. Eugenol possesses significant antioxidant, anti-inflammatory and cardiovascular properties, in addition to analgesic and local anesthetic activity. The metabolism and pharmacokinetics of the compound in humans have been studied. Eugenol has also been used as a penetration enhancer. The compound is a very promising candidate for versatile applications, and the design of new drugs based on the pharmacological effects of eugenol could be beneficial. PMID:21299140

  5. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis.

    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

  6. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

    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.

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

    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

  8. Pharmacological actions of statins: potential utility in COPD

    T. E. Eaton

    2009-12-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-B mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1 Inhibition of cytokine production (tumour necrosis factor-, interleukin (IL-6 and IL-8 and neutrophil infiltration into the lung; 2 inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3 antioxidant and anti-inflammatory (IL-6 mediated effects on skeletal muscle; 4 reduced inflammatory response to pulmonary infection; and 5 inhibition of the development (or reversal of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

  9. Pharmacological actions of statins: potential utility in COPD.

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  10. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

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

    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 ph...

  11. CURCUMIN- PHARMACOLOGICAL ACTIONS AND ITS ROLE IN DENTISTRY

    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.   

  12. Pharmacological effects of Sapindus mukorossi.

    Upadhyay, Aparna; Singh, D K

    2012-01-01

    Sapindus mukorossi is an extremely valuable medicinal plant, distributed in tropical and sub-tropical regions of Asia. The aim of present review is to form a short compilation of the phytochemical composition and pharmacological properties of this multipurpose tree. The main phytoconstituents isolated and identified from different parts of this plant are triterpenoidal saponins of oleanane, dammarane and tirucullane type. The structure and chemical names of all the types of triterpenoidal saponins reported in Sapindus mukorossi are included in this review. Many research studies have been conducted to prove the plant's potential as being spermicidal, contraceptive, hepatoprotective, emetic, anti-inflammatory and anti-protozoal. The present review highlights some of the salient pharmacological uses of Sapindus mukorossi. PMID:22983291

  13. Pharmacological effects of Sapindus mukorossi

    Aparna Upadhyay

    2012-10-01

    Full Text Available Sapindus mukorossi is an extremely valuable medicinal plant, distributed in tropical and sub-tropical regions of Asia. The aim of present review is to form a short compilation of the phytochemical composition and pharmacological properties of this multipurpose tree. The main phytoconstituents isolated and identified from different parts of this plant are triterpenoidal saponins of oleanane, dammarane and tirucullane type. The structure and chemical names of all the types of triterpenoidal saponins reported in Sapindus mukorossi are included in this review. Many research studies have been conducted to prove the plant's potential as being spermicidal, contraceptive, hepatoprotective, emetic, anti-inflammatory and anti-protozoal. The present review highlights some of the salient pharmacological uses of Sapindus mukorossi.

  14. Pharmacological effects of Sapindus mukorossi

    Aparna Upadhyay; D K Singh

    2012-01-01

    Sapindus mukorossi is an extremely valuable medicinal plant, distributed in tropical and sub-tropical regions of Asia. The aim of present review is to form a short compilation of the phytochemical composition and pharmacological properties of this multipurpose tree. The main phytoconstituents isolated and identified from different parts of this plant are triterpenoidal saponins of oleanane, dammarane and tirucullane type. The structure and chemical names of all the types of triterpenoidal sap...

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

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. PMID:26174880

  16. Pharmacological effects of medicinal plants on skin

    Zohreh Bakhtiyari, MSc; Mohammadreza Radan, MD

    2013-01-01

    Skin is one of the most sensitive parts of the body and is important to maintain the beauty of man. Herbal products have fewer side effects than chemicals and have pharmacological effects on the skin, so are used in cosmetic preparations. Books, articles and electronic databases including ISI Web of Science, PubMed, Magiran and IranMedex were searched to identify plants with positive effects on the skin, regardless of adverse effects and their interactions. A number of plants which were...

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

    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…

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

    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

  19. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

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

    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.

  1. [Comparison with the pharmacological actions of Morinda officinalis, Damnacanthus officinarum and Schisandra propinqua].

    Qiao, Z S; Wu, H; Su, Z W

    1991-07-01

    There are three kinds of plants, Morinda officinalis (1), Damnacanthus officinarum (2), and Schisandra propinqua (3) whose roots have been used since the ancient time. In this paper, some of their pharmacological actions that are related to tonifying and invigorating Yang were examined and compared. The body weight, the thymus weight, the amount of leukocyte in the blood, and the continuing swimming times of the young mice could be increased with the oral administration of the water extractions of (1) and (2) (P less than 0.05-0.001). The Rt of M-receptor in the brains of the hypothyroidism mice were decreased after administration of the water extracts of (1) and (2) (P less than 0.05). (1) could also increased the amount of leukocyte in the blood of leukocytopenia mice caused by radiation of gamma-ray (P less than 0.01). (3) has not shown the obvious effects (P greater than 0.05). The results indicate that (1) and (2) have the ability of anti-fatigue, improving the immunological action of the young mice, and reducing the excitability of the para-sympathetic nervous system of the hypothyroidism mice through decreasing the Rt of M-receptor in their brains. All of them did not show acute toxicity, inducing mutation, and sexual hormone like actions. PMID:1914038

  2. Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

    Al-Taweel, A M; Fawzy, G A; Perveen, S; El Tahir, K E H

    2013-09-01

    The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws. PMID:23780497

  3. Effective actions near singularities

    We study the heterotic string compactified on K3x T2 near the line T=U, where the effective action becomes singular due to an SU(2) gauge symmetry enhancement. By 'integrating in' the light W± vector multiplets we derive a quantum corrected effective action which is manifestly SU(2) invariant and non-singular. This effective action is found to be consistent with a residual SL(2,Ζ) quantum symmetry on the line T=U. In an appropriate decompactification limit, we recover the known SU(2) invariant action in five dimensions. (author)

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

    Caviola, L.; Faber, NS

    2015-01-01

    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 consisten...

  5. Pills or Push-Ups? Effectiveness and Public Perception of Pharmacological and Non-Pharmacological Cognitive Enhancement

    Caviola, Lucius; Nadira S. Faber

    2015-01-01

    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 consisten...

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

    Lucius eCaviola; Nadira S. Faber

    2015-01-01

    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 consisten...

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

    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.

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

    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. PMID:20942780

  9. Life-history responses of Daphnia magna Straus to binary mixtures of toxic substances: Pharmacological versus ecotoxicological modes of action

    Two prevailing theoretical models: concentration addition (CA) and independent action (IA), predict mixture toxicity on the basis of known toxicities of the mixture components. To date, both models have been in most occasions evaluated using unicellular in vivo responses or biochemical in vitro responses. However, when considering more complex models such as the whole organism physiology or life-history traits, the dominant ecotoxicological mode of action, based on the exposure concentrations at which various toxicological effects become operative at the level of whole organism, should be considered. Offspring production in Daphnia magna is driven by the resources acquired from food, and the number of live offspring produced by an organism is the result of two independent factors: the number of eggs produced and the percentage of eggs that survive egg development. In this study joint toxicity effects on offspring production in D. magna were tested using binary mixtures of toxic contaminants known to specifically impair food acquisition (λ-cyhalothrin and cadmium) or to cause egg mortality during development (3,4 dichloroaniline). Tests were performed using a simplified 10-day reproduction assay initiated with gravid females. The results obtained indicate that irrespective of their primary pharmacological mode of action, the joint toxicity of cadmium and λ-cyhalothrin was predicted by the CA model, whereas the joint toxicity of cadmium and 3,4 dichloroaniline was predicted by the IA model. Thus, the results obtained indicate that for life-history traits such as reproduction responses, the dominant ecotoxicological rather than the pharmacological mode of action should be used for predicting joint mixture effects

  10. Pharmacological Actions of Glucagon-Like Peptide-1, Gastric Inhibitory Polypeptide, and Glucagon.

    Sekar, R; Singh, K; Arokiaraj, A W R; Chow, B K C

    2016-01-01

    Glucagon family of peptide hormones is a group of structurally related brain-gut peptides that exert their pleiotropic actions through interactions with unique members of class B1 G protein-coupled receptors (GPCRs). They are key regulators of hormonal homeostasis and are important drug targets for metabolic disorders such as type-2 diabetes mellitus (T2DM), obesity, and dysregulations of the nervous systems such as migraine, anxiety, depression, neurodegeneration, psychiatric disorders, and cardiovascular diseases. The current review aims to provide a detailed overview of the current understanding of the pharmacological actions and therapeutic advances of three members within this family including glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. PMID:27572131

  11. 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

    Hadrup, Niels

    2014-01-01

    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...

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

    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. PMID:26778456

  13. Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse.

    Frank, M; Weckman, T J; Wood, T; Woods, W E; Tai, C L; Chang, S L; Ewing, A; Blake, J W; Tobin, T

    1990-11-01

    Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. These effects were transient, and the animals appeared normal within 30 mins of dosing. Treated horses were tested in a variable interval responding apparatus 30 mins after dosing and no residual stimulation or depressant effects of hordenine were apparent. Animals dosed orally with 2.0 mg/kg bwt of hordenine showed no changes in heart rate, respiratory rate, basal body temperature or behaviour. After iv injection of hordenine, (2.0 mg/kg bwt) plasma reached a maximum value of about 1.0 micrograms/ml, and declined thereafter in a biexponential fashion. Kinetics of plasma concentration satisfied the concept of a two compartment open system, with an alpha-phase half-life of about 3 mins, and a beta-phase half-life of about 35 mins. Total urinary concentrations of hordenine (free and conjugated) peaked at about 400 micrograms/ml, and then declined exponentially to background levels by 24 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2269269

  14. Parameter Trajectory Analysis to Identify Treatment Effects of Pharmacological Interventions

    Tiemann, Christian A.; Vanlier, Joep; Oosterveer, Maaike H.; Albert K Groen; Hilbers, Peter A. J.; Natal A W van Riel

    2013-01-01

    The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological) treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT), to analyze the long-t...

  15. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects.

    Pfister, Christina; Dawzcynski, Horst; Schingale, Franz-Josef

    2016-09-01

    A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression. PMID:27267968

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

    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. PMID:23103297

  17. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity.

    Ghanem, Carolina I; Pérez, María J; Manautou, José E; Mottino, Aldo D

    2016-07-01

    Acetaminophen (APAP) is a well-known analgesic and antipyretic drug. It is considered to be safe when administered within its therapeutic range, but in cases of acute intoxication, hepatotoxicity can occur. APAP overdose is the leading cause of acute liver failure in the northern hemisphere. Historically, studies on APAP toxicity have been focused on liver, with alterations in brain function attributed to secondary effects of acute liver failure. However, in the last decade the pharmacological mechanism of APAP as a cannabinoid system modulator has been documented and some articles have reported "in situ" toxicity by APAP in brain tissue at high doses. Paradoxically, low doses of APAP have been reported to produce the opposite, neuroprotective effects. In this paper we present a comprehensive, up-to-date overview of hepatic toxicity as well as a thorough review of both toxic and beneficial effects of APAP in brain. PMID:26921661

  18. Carum copticum L.: a herbal medicine with various pharmacological effects.

    Boskabady, Mohammad Hossein; Alitaneh, Saeed; Alavinezhad, Azam

    2014-01-01

    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. PMID:25089273

  19. Pharmacological Drug Delivery Strategies for Improved Therapeutic Effects: Recent Advances.

    Savaliya, Reema; Singh, Poornima; Singh, Sanjay

    2016-01-01

    The latest pharmacologic research has resulted number of new molecules with the potential to modernize the prevention or treatment of different complex diseases, including cancer. The therapeutics generally include moieties such as proteins, drugs and genes, etc. Current activities in the pharmacological field include the development of novel drug-delivery systems to overcome pharmacokinetic glitches such as limited bioavailability, unwanted distribution, drug resistant, and stability, etc. Therefore, to address these issues various biotechnological and pharmacological techniques has been introduced. However, effective drug delivery with improved efficacy remains challenging. This review is focused towards different strategies such as physical and biological methods for efficacious delivery at desired tissues and even sub-cellular targeting. Emphasis is also given about nanotechnology based drug or gene delivery strategies and co-delivery of drug-drug; gene-gene or combinations of drug-gene, etc. are the current cuttingedge methods, which are under clinical or pre-clinical stage of research. Uses of biodegradable materials, such as liposomes and polymeric particles are another class of drug delivery vehicles, which have shown tremendous success, are also discussed. Towards the end, future directions of pharmacological drug delivery methods have also been summarized. PMID:26654439

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

    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...... is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus...... certain mode of action of the drug in cluster headache....

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

    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.

  2. [Research progress of trans-cinnamaldehyde pharmacological effects].

    Zhang, Li-qing; Zhang, Zhan-gang; Fu, Yan; Xu, Ying

    2015-12-01

    Trans-cinnamaldehyde, the main component of volatile oil from cassia twig or Cinnamomum cassia, which is a traditional Chinese herbal medicine. Trans-cinnamaldehyde is a kind olefine aldehyde of organic compounds and has many pharmacological properties, such as anti-inflammatory, anti-tumor, anti-bacterial, antidiabetic, anti-obesity, and neuroprotection etc. The compound has preventive and therapeutic effects on the nervous system, cardiovascular, cancer, diabetes and other diseases. Trans-cinnamaldehyde, as a preventive care of nature medicine, has great clinical and market potential. This paper gives a review about the pharmacological effects and mechanism of trans-cinnamaldehyde researched in the latest five years. We hope to provide some basic information for further research on trans-cinnamaldehyde. PMID:27141665

  3. Effects of Security actions

    Bergman, Ramona; Andersson-Sköld, Yvonne; Nyberg, Lars; Johansson, Magnus

    2010-05-01

    In a project funded by the Swedish Civil Contingencies Agency, the effort and work to reduce different kinds of accidents are being evaluated. The project wants to illuminate the links between actions and outcome, so we can learn from today's performance and in the future select more effective measures and overall deal with accidents more efficiently. The project ESS covers the field of frequent accidents such as sliding accidents at home, in house fires and less common accidents such as chemical and land fill accidents up to even more rare accidents such as natural accidents and hazards. In the ESS project SGI (Swedish geotechnical institute) will evaluate the work and effort concerning various natural hazards limited to landslides, erosion and flooding. The aim is to investigate how municipalities handle, especially prevention, of such natural disasters today. The project includes several aspects such as: • which are the driving forces for risk analysis in a municipality • do one use risk mapping (and what type) in municipal risk analysis • which aspects are most important when selecting preventive measures • in which way do one learn from past accidents • and from previous accidents elsewhere, by for example use existing databases • etc There are many aspects that play a role in a well-functioning safety promotion work. The overall goal is to examine present work and activities, highlight what is well functioning and identify weak points. The aim is to find out where more resources are needed and give suggestions for a more efficient security work. This includes identification of the most efficient "tools" in use or needed. Such tools can be education, directives, funding, more easily available maps and information regarding previous accidents and preventive measures etc. The project will result in recommendations for more effective ways to deal with landslides, erosion and flooding. Since different kinds of problems can occur depending on level of

  4. Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

    Christian A Tiemann

    Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

  5. Effects of various pharmacological agents on exposed heart of uromastix hardwickii

    Background: The pharmacological and physiological studies on cardiac activity of reptiles specifically of Uromastix hardwickii are scarcely available in literature, as well as the effects of parasympathetic and sympathetic agonists together are also not available. Therefore, the mechanical and electrophysiological effects of pharmacological agents, like Physostigmine and its effects before and after Adrenaline administration were observed on the exposed and intact heart of a reptile, Uromastix hardwickii. Method: To work on exposed heart of Uromastix hardwickii, Physostigmine and Adrenaline were prepared by dissolving 0.01 gm in 10 ml of distilled water. Oscillograph was used to record the mechanical and electrical activity of intact heart through isotonic transducer. Result: Physostigmine was found to produce significant effect on Systolic Force (SF), Duration of cardiac cycle (DCC) and Duration of Phase 4 (DP4). Significant effect of Physostigmine was also observed on heart rate (HR) before Adrenaline administration and on DP4 after Adrenaline administration. Conclusion: It was confirmed that Physostigmine does not exhibit its normal effect on Amplitude of Action Potential, cardiac cycle (CC), Duration of action potential (DAP), Plateau Duration and DP4. Physostigmine is affecting the cardiac activity of this reptile without inhibiting the cholinesterase and not accumulating the Acetylcholine. It modulates the effects of Adrenaline when used before the administration of Adrenaline. (author)

  6. Research Progress of Pharmacological Action of Hawthorn Leaves Flavonoids%山楂叶总黄酮药理作用研究进展

    于栋华; 包顺茹; 于纯淼; 刘树民

    2013-01-01

    我国山楂叶资源丰富,价廉易得,而山楂叶总黄酮为山楂叶提取物中的主要成分,具有广泛的药理作用.现就其对心脑血管、降脂降糖降压、抗氧化等方面的研究进展做一综述,并对应用前景进行了展望.%The hawthorn leaves resource in our country is abundant and easy to get. As the major component of hawthorn leaves, hawthorn leaves flavonoids ( HLF ) has an extensive pharmacological effect. This article reviews the research progress of its pharmacological action on cardio-cerebral-vascular, conquering the blood lipid, blood glucose sugar and blood pressure, antioxidation and so on. Moreover, it puts forward the prospects for its application.

  7. How MDMA's pharmacology and pharmacokinetics drive desired effects and harms.

    Michael White, C

    2014-03-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment. PMID:24431106

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

    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.

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

    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).

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

    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

  11. The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

    Chen, John; Patel, Roshni; Friedman, Theodore C.; Jones, Kevin S

    2010-01-01

    Dizocilpine maleate (MK-801) is one of several NMDA receptor antagonists that is widely used to pharmacologically model the symptoms of psychosis and schizophrenia in animals. MK-801 elicits behaviors in adult zebrafish (Danio rerio) that are phenotypically consistent with behaviors observed in humans and rodents exposed to tbhe drug. However, the molecular and cellular processes that mediate the psychotomimetic, cognitive and locomotive behaviors of MK-801 are unclear. We exposed zebrafish l...

  12. The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

    Chen, John; Patel, Roshni; Friedman, Theodore C.; Jones, Kevin S

    2010-01-01

    Dizocilpine maleate (MK-801) is one of several NMDA receptor antagonists that is widely used to pharmacologically model the symptoms of psychosis and schizophrenia in animals. MK-801 elicits behaviors in adult zebrafish (Danio rerio) that are phenotypically consistent with behaviors observed in humans and rodents exposed to the drug. However, the molecular and cellular processes that mediate the psychotomimetic, cognitive and locomotive behaviors of MK-801 are unclear. We exposed zebrafish la...

  13. Developmental paediatric anaesthetic pharmacology

    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...

  14. Pharmacological and therapeutic effects of Mentha Longifolia L. and its main constituent, menthol

    Peyman Mikaili; Sina Mojaverrostami; Milad Moloudizargari; Shahin Aghajanshakeri

    2013-01-01

    Mentha longifolia (wild mint) is a popular folk remedy. Some parts of this plant have been used in traditional medicine of Iran and other countries. Many studies have shown various pharmacological and therapeutic effects of the plant. Our aim in preparing this study was to review the traditional uses of M. longifolia together with the pharmacological and therapeutic effects of its entire extract and major compounds. Mentha longifolia is an herb with a wide range of pharmacological properties ...

  15. Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals

    Pieramico, Valentina; Esposito, Roberto; Cesinaro, Stefano; Frazzini, Valerio; Sensi, Stefano L.

    2014-01-01

    Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia. PMID:25228860

  16. Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals.

    Pieramico, Valentina; Esposito, Roberto; Cesinaro, Stefano; Frazzini, Valerio; Sensi, Stefano L

    2014-01-01

    Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia. PMID:25228860

  17. Citalopram--a review of pharmacological and clinical effects.

    Bezchlibnyk-Butler, K; Aleksic, I; Kennedy, S. H.

    2000-01-01

    OBJECTIVE: To provide clinicians with a critical evaluation of citalopram, a selective serotonin reuptake inhibitor (SSRI) that has been available in Canada since March 1999. DATA SOURCES: Commercial searches (MEDLINE and BiblioTech) and an "in-house" search (InfoDrug) were used to find published English-language references for clinical and preclinical publications. There was no restriction of publication dates. Primary index terms used were: pharmacological properties, receptors, pharmacolog...

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

    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.

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

    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.

  20. 紫菀的化学成分及其药理活性研究进展%Advances on chemical components and pharmacological actions of Aster tataricus

    房慧勇; 单高威; 秦桂芳; 甄林娜; 李旻辉; 郝丽静

    2012-01-01

      紫菀具有良好的润肺、祛痰、止咳效果,通过查阅国内外相关文献,综述了其化学成分和化痰镇咳、抗肿瘤等方面的药理作用,为紫菀的综合开发利用提供参考。%  Aster tataricus L. f. has a good effect upon moistening lung, eliminating phlegm, and suppressing cough. The literature reviews its chemical compositions and pharmacological action of eliminating phlegm, anti-tumor and etc.. The literature could provide reference for development and utilization of Aster tataricus.

  1. Effectiveness of integrated teaching module in pharmacology among medical undergraduates

    Yadav, Preeti P; Chaudhary, Mayur; Patel, Jayshree; Shah, Aashal; Kantharia, ND

    2016-01-01

    Context: Over the years with advancement of science and technology, each subject has become highly specialized. Teaching of medical students has still remained separate in various departments with no scope of integration in majority of medical institutes in India. Study was planned to have an experience of integration in institute and sensitize faculty for integrated teaching–learning (TL) method. Aims: To prepare and test effectiveness of integrated teaching module for 2nd year MBBS student in pharmacology and to sensitize and motivate faculties toward advantages of implementing integrated module. Settings and Design: Education intervention project implemented 2nd year MBBS students of Government Medical College and New Civil Hospital, Surat. Subjects and Methods: Students of second MBBS were divided into two groups. One group was exposed to integrated teaching sessions and another to traditional method. Both the groups were assessed by pre- and post-test questionnaire, feedback and focus group discussions were conducted to know their experience about process. Results: A total of 165 students of the 2nd year MBBS were exposed to the integrated teaching module for two topics in two groups. One group was taught by traditional teaching, and another group was exposed to the integrated TL session. Both the groups have shown a significant improvement in posttest scores but increase in mean score was more in integrated group. During analysis of feedback forms, it was noted that students preferred integrated TL methods since they help in better understanding. Faculty feedback shows consensus over the adaptation of integrated TL methods. Conclusions: Integrated TL sessions were well-appreciated by students and faculties. To improve the critical reasoning skills and self-directed learning of students, integrated TL is highly recommended for must know areas of curriculum.

  2. PHYTOCHEMICAL, PHARMACOLOGICAL AND PHARMACOKINETICS EFFECTS OF ROSMARINIC ACID

    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.

  3. Histamine reverses IL-5-Afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

    Hasala, Hannele; Giembycz, Mark A.; Janka-Junttila, Mirkka; Moilanen, Eeva; Kankaanranta, Hannu

    2008-01-01

    Histamine reverses IL-5-Afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine correspondence: Corresponding author. Tel.: +358335517318; fax: +358335518082. (Kankaanranta, Hannu) (Kankaanranta, Hannu) The Immunopharmacology Research Group--> , Medical School--> , University of Tampere--> , Tampere--> - FINLAND (Hasala, H...

  4. Effect of metal complexation to anti-inflammatory over the action against oxidative and free radicals: ketoprofen action

    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)

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

    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. .

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

    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.

  7. Structural and Pharmacological Effects of Ring-Closing Metathesis in Peptides

    Pål Rongved

    2010-09-01

    Full Text Available Applications of ring-closing alkene metathesis (RCM in acyclic α- and β-peptides and closely related systems are reviewed, with a special emphasis on the structural and pharmacological effects of cyclization by RCM.

  8. Structural and Pharmacological Effects of Ring-Closing Metathesis in Peptides

    Pål Rongved; Øyvind Jacobsen; Jo Klaveness

    2010-01-01

    Applications of ring-closing alkene metathesis (RCM) in acyclic α- and β-peptides and closely related systems are reviewed, with a special emphasis on the structural and pharmacological effects of cyclization by RCM.

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

    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.

  10. Mechanisms of Action in Cognitive-Behavioral and Pharmacological Interventions for Obesity and Bulimia Nervosa.

    Craighead, Linda W.; Agras, W. Stewart

    1991-01-01

    Summarizes data pertaining to separate and combined effects of cognitive-behavioral and psychopharmacologic treatments for obesity and bulimia nervosa. Anorexiant medication appears to enhance restraint and facilitates weight loss with behavioral interventions in the treatment of obesity, but relapse occurs once medication is withdrawn.…

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

    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

  12. Pharmacological Action of Mentha piperita on Lipid Profile in Fructose-Fed Rats.

    Mani Badal, Rajendra; Badal, Divya; Badal, Pourush; Khare, Ashish; Shrivastava, Jyoti; Kumar, Vinod

    2011-01-01

    Cardiovascular diseases with an incidence of approximately 50% are the main causes of death in most advanced countries and an increasing trend in the developing world as well. The World Health Organization estimates that 12 million people per year worldwide die from cardiovascular diseases. Cardiovascular diseases are becoming an increasing problem worldwide and hypercholesterolemia has been correlated for coronary heart diseases. Nearly all lipoproteins are involved in this process including cholesterol carried by very low density lipoproteins (VLDL), remnant lipoproteins and low density lipoproteins (LDL). Currently, available hypolipidemic drugs have been associated with the number of side effects. Herbal treatment for hyperlipidemia poses no side effects and is relatively cheap and locally available. In view of this, the present study was carried out to investigate the effect of Menthe piperita on serum lipid levels of albino rats. Mentha piperita aqueous extract (100 mg/Kg, 250 mg/Kg p.o. daily) was fed for 3 weeks on fructose-fed rats and the levels of glucose, cholesterol, triglycerides, very low density lipoprotein, low density lipoprotein, and atherogenic index was measured. Twenty-four male Sprague Dawley rats were divided into four groups (6 per group). The results of present study indicate that Mentha piperita had significant beneficial effects against fructose-induced hyperlipidemia and showed good antioxidant activity. The aqueous extract of the plant produced a significant decrease (p < 0.05) in elevated levels of glucose, cholesterol, triglycerides, very low density lipoprotein, low density lipoprotein and atherogenic index and also increased the high density lipoprotein cholesterol levels and HDL-ratio without affecting serum insulin levels in fructose-fed rats. PMID:24250421

  13. Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

    Antonio V Gaddi

    2010-07-01

    Full Text Available Antonio V Gaddi1, Arrigo FG Cicero1, Giovanni Gambaro21Atherosclerosis and Metabolic disease Research Unit, Internal Medicine, Aging and Kidney diseases Dept., University of Bologna, Italy; 2Nephrology and Dialysis Unit, Gemelli University Hospital, Sacred Heart Catholic University, Rome, ItalyAbstract: A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin–angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment.Keywords: glycosaminoglycans, sulodexide, albuminuria, proteinuria, diabetic nephropathy

  14. A novel method for imaging the pharmacological effects of antibiotic treatment on Clostridium difficile.

    Endres, Bradley T; Bassères, Eugénie; Memariani, Ali; Chang, Long; Alam, M Jahangir; Vickers, Richard J; Kakadiaris, Ioannis A; Garey, Kevin W

    2016-08-01

    Clostridium difficile is a significant cause of nosocomial-acquired infection that results in severe diarrhea and can lead to mortality. Treatment options for C. difficile infection (CDI) are limited, however, new antibiotics are being developed. Current methods for determining efficacy of experimental antibiotics on C. difficile involve antibiotic killing rates and do not give insight into the drug's pharmacologic effects. Considering this, we hypothesized that by using scanning electron microscopy (SEM) in tandem to drug killing curves, we would be able to determine efficacy and visualize the phenotypic response to drug treatment. To test this hypothesis, supraMIC kill curves were conducted using vancomycin, metronidazole, fidaxomicin, and ridinilazole. Following collection, cells were either plated or imaged using a scanning electron microscope (SEM). Consistent with previous reports, we found that the tested antibiotics had significant bactericidal activity at supraMIC concentrations. By SEM imaging and using a semi-automatic pipeline for image analysis, we were able to determine that vancomycin and to a lesser extent fidaxomicin and ridinilazole significantly affected the cell wall, whereas metronidazole, fidaxomicin, and ridinilazole had significant effects on cell length suggesting a metabolic effect. While the phenotypic response to drug treatment has not been documented previously in this manner, the results observed are consistent with the drug's mechanism of action. These techniques demonstrate the versatility and reliability of imaging and measurements that could be applied to other experimental compounds. We believe the strategies laid out here are vital for characterizing new antibiotics in development for treating CDI. PMID:27108094

  15. Anti-pressor effects of whole body exposure to static magnetic field on pharmacologically induced hypertension in conscious rabbits.

    Okano, Hideyuki; Ohkubo, Chiyoji

    2003-02-01

    Acute effects of whole body exposure to static magnetic field (SMF) on pharmacologically induced hypertension in a conscious rabbit were evaluated. Hypertensive and vasoconstrictive actions were induced by norepinephrine (NE) or a nonselective nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME). The hemodynamics in a central artery of the ear lobe was measured continuously and analyzed by penetrating microphotoelectric plethysmography (MPPG). Concurrently, blood pressure (BP) changes in a central artery, contralateral to that of the MPPG measured ear lobe, were monitored. Magnetic flux densities were 5.5 mT (Bmax), the magnetic gradient peaked in the throat at the level of approximately 0.09 mT/mm, and the duration of exposure was 30 min. The results demonstrated that under normal physiological conditions without treatment of pharmacological agents, there were no statistically significant differences in the hemodynamics and BP changes between the sham and the SMF exposure alone. Under pharmacologically induced hypertensive conditions, the whole body exposure to nonuniform SMF with peak magnetic gradient in the carotid sinus baroreceptor significantly attenuated the vasoconstriction and suppressed the elevation of BPs. These findings suggest that antipressor effects of the SMF on the hemodynamics under NE or l-NAME induced high vascular tone might be, in part, dependent on modulation of NE mediated response in conjunction with alteration in NOS activity, thereby modulating BPs. PMID:12524681

  16. In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.

    Rolf, Michael G; Curwen, Jon O; Veldman-Jones, Margaret; Eberlein, Cath; Wang, Jianyan; Harmer, Alex; Hellawell, Caroline J; Braddock, Martin

    2015-10-01

    Off-target pharmacology may contribute to both adverse and beneficial effects of a new drug. In vitro pharmacological profiling is often applied early in drug discovery; there are fewer reports addressing the relevance of broad profiles to clinical adverse effects. Here, we have characterized the pharmacological profile of the active metabolite of fostamatinib, R406, linking an understanding of drug selectivity to the increase in blood pressure observed in clinical studies. R406 was profiled in a broad range of in vitro assays to generate a comprehensive pharmacological profile and key targets were further investigated using functional and cellular assay systems. A combination of traditional literature searches and text-mining approaches established potential mechanistic links between the profile of R406 and clinical side effects. R406 was selective outside the kinase domain, with only antagonist activity at the adenosine A3 receptor in the range relevant to clinical effects. R406 was less selective in the kinase domain, having activity at many protein kinases at therapeutically relevant concentrations when tested in multiple in vitro systems. Systematic literature analyses identified KDR as the probable target underlying the blood pressure increase observed in patients. While the in vitro pharmacological profile of R406 suggests a lack of selectivity among kinases, a combination of classical searching and text-mining approaches rationalized the complex profile establishing linkage between off-target pharmacology and clinically observed effects. These results demonstrate the utility of in vitro pharmacological profiling for a compound in late-stage clinical development. PMID:26516587

  17. [Pharmacological effects of CM6912 and its main metabolites].

    Morishita, H; Kushiku, K; Furukawa, T; Yamaki, Y; Izawa, M; Shibazaki, Y; Shibata, U

    1985-07-01

    Pharmacodynamic effects of ethyl 7-chloro-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4- benzodiazepine-3-carboxylate (CM6912), a new benzodiazepine derivative, and its main metabolites (CM6913 = M1, CM7116 = M2) on the peripheral systems were investigated in several species of animals. In pentobarbital-anesthetized rabbits, CM6912 and M2 (1 or 5 mg/kg, i.v.) had little effect on blood pressure, heart rate and ECG, but it slightly reduced the respiration rate. M1 decreased the heart rate without affecting respiration, blood pressure and ECG. In conscious rabbits, CM6912 and M2 (1 mg/kg, i.v.) did not affect respiration, blood pressure, heart rate and ECG, but M1 (1 mg/kg, i.v.) increased the heart rate. CM6912 (5 or 30 mg/kg), when administered orally, also increased heart rate. In pentobarbital-anesthetized dogs, CM6912 and its metabolites (5 mg/kg, i.v.) decreased respiration and heart rate without affecting blood pressure and ECG. CM 6912 (5 mg/kg, i.v.) did not affect cardiovascular responses to the carotid occlusion, vagus stimulation, and pre- and post-ganglionic stimulation of cardiac ganglion in anesthetized dogs. CM6912 and its metabolites affected neither the spontaneous contraction nor the heart rate of isolated rabbit atria. These compounds also had no action on isolated aortic strips from rabbits. CM6912 and its metabolites did not affect the muscle tone of isolated guinea pig intestine, and it had no effects on the contractile responses to acetylcholine, histamine, serotonin and barium chloride. In isolated rabbit intestine, CM6912 and M2 slightly reduced the amplitude of contraction, while M1 had no effect. CM6912 and its metabolites did not affect the spontaneous motility of isolated non-pregnant and pregnant rat uteri as well as in situ non-pregnant rat uterus and isolated guinea pig vas deferens, including the contractile response to adrenaline. CM6912 and M2 relaxed isolated guinea pig trachea strips only at high concentrations. CM6912 and its

  18. Effect of Pharmacologically-Induced Hypovolemia on Aerobic Capacity

    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, pbpm). The AUC for VO2 and HR was different (p<0.05) between conditions only in the highest quartile: HR was 4% higher and VO2 was 5% lower during the hypovolemia condition. Conclusion: The mean difference in VO2pk (-12%) between normovolemia and hypovolemia was similar to the mean difference in PV (-17%). Similar decreases in PV and VO2pk have been observed following short duration space flight, suggesting that pharmacologically-induced PV loss can be used to model

  19. Effect of Pharmacologically-Induced Hypovolemia on Aerobic Capacity

    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, p<0.05) and VO2pk (3.30+/-0.67 vs. 2.90+/-0.57 L.min(sup -1), p<0.05) were lower during hypovolemia than during normovolemia, but peak HR was not different (187+/-5 vs. 187+/-5 bpm). The AUC for VO2 and HR was different (p<0.05) between conditions only in the highest quartile: HR was 4% higher and VO2 was 5% lower during the hypovolemia condition. Conclusion: The mean difference in VO2pk (-12%) between normovolemia and hypovolemia was similar to the mean difference in

  20. Wilsonian Effective Action of Superstring Theory

    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.

  1. The pharmacological effect of Bothrops neuwiedii pauloensis (jararaca-pintada snake venom on avian neuromuscular transmission

    C.R. Borja-Oliveira

    2003-05-01

    Full Text Available The neuromuscular effects of Bothrops neuwiedii pauloensis (jararaca-pintada venom were studied on isolated chick biventer cervicis nerve-muscle preparations. Venom concentrations of 5-50 µg/ml produced an initial inhibition and a secondary increase of indirectly evoked twitches followed by a progressive concentration-dependent and irreversible neuromuscular blockade. At venom concentrations of 1-20 µg/ml, the responses to 13.4 mM KCl were inhibited whereas those to 110 µM acetylcholine alone and cumulative concentrations of 1 µM to 10 mM were unaffected. At venom concentrations higher than 50 µg/ml, there was pronounced muscle contracture with inhibition of the responses to acetylcholine, KCl and direct stimulation. At 20-24ºC, the venom (50 µg/ml produced only partial neuromuscular blockade (30.7 ± 8.0%, N = 3 after 120 min and the initial inhibition and the secondary increase of the twitch responses caused by the venom were prolonged and pronounced and the response to KCl was unchanged. These results indicate that B.n. pauloensis venom is neurotoxic, acting primarily at presynaptic sites, and that enzyme activity may be involved in this pharmacological action.

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

    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. PMID:12660312

  3. On String Field Theory and Effective Actions

    Giveon, Amit

    1992-01-01

    A truncation of string field theory is compared with the duality invariant effective action of $D=4, N=4$ heterotic strings to cubic order. The three string vertex must satisfy a set of compatibility conditions. Any cyclic three string vertex is compatible with the $D=4, N=4$ effective field theory. The effective actions may be useful in understanding the non--polynomial structure and the underlying symmetry of covariant closed string field theory, and in addressing issues of background indep...

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

    Tahara, Atsuo; Takasu, Toshiyuki; Yokono, Masanori; Imamura, Masakazu; Kurosaki, Eiji

    2016-03-01

    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. PMID:26970780

  5. Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi.

    Rogliani, Paola; Calzetta, Luigino; Ora, Josuel; Lipsi, Roberto; Segreti, Andrea; Matera, Maria Gabriella; Cazzola, Mario

    2015-08-15

    Preclinical studies suggested that aclidinium and glycopyrronium might have a faster onset of action than tiotropium. In this study we assessed the onset of action of aclidinium and glycopyrronium versus tiotropium, all administered at the approved clinical doses, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and in human isolated bronchi by using different concentrations. Sixteen COPD patients inhaled single doses of aclidinium 400µg, glycopyrronium 50μg and tiotropium 18µg and FEV1 was measured to assess their onset of action. In human isolated bronchi the time to evoke half maximal relaxation of transmural stimulation was tested from 10nM to 1µM for each drug. Nine, eight and twelve patients did not achieve 15% increase of FEV1 after inhalation of aclidinium, glycopyrronium and tiotropium, respectively. Aclidinium (15.6±7.5min) and glycopyrronium (17.9±10.4min) enhanced 15% FEV1 more rapidly than tiotropium (42.5±19.4min), with no significant difference (P>0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of action (10nM: 8.2±1.3min, 100nM: 7.1±2.1min, 1μM: 3.4±0.4min) that was faster compared to that induced by aclidinium (1μM: 6.4±0.5min) and tiotropium (1μM: 8.4±1.1min) (Pglycopyrronium was faster than that induced by tiotropium, but since our analysis was restricted to the acute effect of these LAMAs and the inhaled doses were not isoeffective, the real differences in their impact on the onset of bronchodilation will be definitely determined after a long-term challenge of these treatments at isoeffective doses in COPD patients. PMID:25952728

  6. [Pharmacological action on emotional sphere with phenazepam and caffeine changes preference of ethanol in Wistar male rats].

    2014-01-01

    Earlier we have shown that essential for formation of preference to alcohol is not that much the initial anxiety level, but rather direction of its change in the process of forced alcoholization. The goal of this work was study of effect of change in the anxiety level on formation of action on the emotional sphere. Out of four groups, for 4 months of experiment, the 1st group had access only to the 10 % ethanol solution; the 2nd group--to the 10% ethanol with addition of 0.4 g/l caffeine; the 3rd - to 10% ethanol with 0.5 mg/l phenazepam; the 4th (control)--only to water. The anxiety level and behavioral parameters were estimated prior to the experiment and after each 5 weeks with aid of the test "the open field". Preference of ethanol was determined with aid of the test "the two-glass sample" before the experiment and each 4 weeks. In experimental groups of rats the long-term consumption of ethanol, of ethanol with caffeine, and of ethanol with phenazepam led to an increase in preference of alcohol as compared with control. A decrease of motor activity at the period of forced alcoholization was found to correlate positively with the low level of preference of alcohol. The rats consuming ethanol with caffeine and sensitive to action of the psychostimulator enhancing anxiety formed faster the preference to alcohol. In rats not sensitive to action of caffeine the preference to alcohol was not formed. Rats sensitive to the sedative action of phenazepam were less anxious and subsequently did not prefer alcohol. In rats not sensitive to phenazepam, anxiety was enhanced and preference to alcohol was formed. PMID:25508949

  7. Pharmacology Information System Ready

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses the development and future of Prophet,'' a specialized information handling system for pharmacology research. It is designed to facilitate the acquisition and dissemination of knowledge about mechanisms of drug action, and it is hoped that it will aid in converting pharmacology research from an empirical to a predictive science. (JR)

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

    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 on sexual function in postmenopausal women. Sufficient evidence for the effects of tibolone on sexual function and dysfunction in postmenopausal women was, until now not available. As tibolone does...

  9. Dissociation of the Pharmacological Effects of THC by mTOR Blockade

    Puighermanal E; Busquets-Garcia A; Gomis-Gonz\\xe1lez M; Marsicano G; Maldonado R; Ozaita A.

    2013-01-01

    The potential therapeutic benefits of cannabinoid compounds have raised interest in understanding the molecular mechanisms that underlie cannabinoid-mediated effects. We previously showed that the acute amnesic-like effects of delta9-tetrahydrocannabinol (THC) were prevented by the subchronic inhibition of the mammalian target of rapamycin (mTOR) pathway. In the present study, we assess the relevance of the mTOR pathway in other acute and chronic pharmacological effects of THC. The rapamycin ...

  10. [STUDYING SOME PHARMACOLOGICAL EFFECTS OF NEW 3-HYDROXYPYRIDINE DERIVATIVE].

    Yasnetsov, V V; Tsublova, E G; Yasnetsov, Vic V; Skachilova, S Ya; Karsanova, S K; Ivanov, Yu V

    2016-01-01

    It was established that a new 3-hydroxypyridine (3-HP) derivative, 2-ethyl-6-methyl-3-hydroxypyridine L-aspartate (3-HP), in small doses (1 and 5 mg/kg) increased physical performance in treadmill and swimming tests on rats. The new substance showed greater or equal effects compared to the reference actoprotector drugs metaprot and ladasten in much higher doses. The gluconeogenesis inhibitor tryptophan significantly (74 ± 5%, p nootropic drug piracetam in a dose of 200 mg/kg, but had equal effect with these drugs in doses of 50 and 800 mg/kg, respectively. 3-HPA (30 mg/kg per day) had neuroprotective effect in rats with brain ischemia and decreased the neurologic deficiency more effectively than mexidol (50 mg/kg per day). PMID:27416675

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

    Phanthunane, Pudtan; Vos, Theo; Whiteford, Harvey; Bertram, Melanie

    2011-01-01

    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 i...

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

    Vos Theo; Phanthunane Pudtan; Whiteford Harvey; Bertram Melanie

    2011-01-01

    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...

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

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

    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

  15. [Dizziness as a side effect of pharmacological therapy].

    Borup Johansen, Nanna; Ayadipanah, Mahnaz; Sonnenschein, Emilie Sofia; Christensen, Hanne Rolighed; Jürgens, Gesche

    2013-11-01

    Dizziness is a well-known side effect of a wide range of drugs. However, the side effects reported in the summary of product characteristics are not exclusively based on placebo-controlled trials. Based on a systematic review of the literature including randomised placebo-controlled clinical trials, antihypertensive combination drugs, methylphenidate, high doses of tramadol and serotonin-norepinephrine reuptake inhibitors were associated with an increased risk of dizziness. Antihypertensive monotherapy and selective serotonin reuptake inhibitors were generally not associated with an increased risk of dizziness when compared with placebo. PMID:24629236

  16. 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

    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.

  17. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

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

    2006-01-01

    the existence of different receptors in the ureter and renal pelvis. The ureteric and pelvic responses to the corresponding neurotransmitters have been determined. It seems that alpha-adrenergic and cholinergic agents are stimulating whereas beta-adrenergic agents inhibit ureteric activity. The effect...

  18. Action-based effects on music perception

    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

  19. Action-based effects on music perception.

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

    2014-01-01

    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

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

    ArvidHerwig

    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.

  1. Effective actions for anomalous hydrodynamics

    We argue that an effective field theory of local fluid elements captures the constraints on hydrodynamic transport stemming from the presence of quantum anomalies in the underlying microscopic theory. Focussing on global current anomalies for an arbitrary flavour group, we derive the anomalous constitutive relations in arbitrary even dimensions. We demonstrate that our results agree with the constraints on anomaly governed transport derived hitherto using a local version of the second law of thermodynamics. The construction crucially uses the anomaly inflow mechanism and involves a novel thermofield double construction. In particular, we show that the anomalous Ward identities necessitate non-trivial interaction between the two parts of the Schwinger-Keldysh contour

  2. Principles of Safety Pharmacology

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

    2008-01-01

    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. Thi...

  3. Chemical compounds and pharmacological effects of Rabdosia excisa

    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.

  4. Pharmacological modulation of late radio-induced side effects

    After normal tissue exposure to radiation therapy, late side effects can occur and may reduce patients' quality of life due to their progressive nature. Late toxicities occurrence is the main limiting factor of radiotherapy. Various biological disorders related to irradiation are involved in the development of late toxicities including fibrosis. The present review will focus on the recent physiopathological and molecular mechanisms described to be involved in the development of late radio-induced toxicities, that provide therapeutic perspective for pharmaco-modulation. (authors)

  5. Effect of vitamin D status on pharmacological treatment efficiency

    Karczmarewicz, Elżbieta; Czekuć-Kryśkiewicz, Edyta; Płudowski, Paweł

    2013-01-01

    At least 80% of the whole Polish population, including prepubertal children and adolescents, adults and seniors, are vitamin D deficient, defined as 25(OH)D < 50 nmol/L. 83% of Polish newborns start their lives at the state of vitamin D deficiency because 78% of their mothers are also deficient. It was observed that treating patient vitamin D deficiency to vitamin D status serum 25(OH)D) 75–100 nmol/L increased effectiveness of therapies in infectious diseases (chronic hepatitis C, tuberculos...

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

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

    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 ph...

  7. Pharmacological classification of the abuse-related discriminative stimulus effects of trichloroethylene vapor

    Shelton, Keith L.; Nicholson, Katherine L.

    2014-01-01

    Inhalants are distinguished as a class primarily based upon a shared route of administration. Grouping inhalants according to their abuse-related in vivo pharmacological effects using the drug discrimination procedure has the potential to provide a more relevant classification scheme to the research and treatment community. Mice were trained to differentiate the introceptive effects of the trichloroethylene vapor from air using an operant procedure. Trichloroethylene is a chlorinated hydrocar...

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

    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. PMID:27485890

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

    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. PMID:24075352

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

    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.

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

    冯筱巍

    2015-01-01

    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.%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 .

  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

    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. Effects of non-pharmacological or pharmacological interventions to promote cognition and brain plasticity in aging individuals

    Valentina ePieramico

    2014-09-01

    Full Text Available Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline.A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia.

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

    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.

  15. Effect of Disposition of Mannich Antimalarial Agents on Their Pharmacology and Toxicology

    Ruscoe, J. E.; Tingle, M. D.; O’Neill, P. M.; S.A. Ward; Park, B K

    1998-01-01

    The use of the antimalarial agent amodiaquine has been curtailed due to drug-induced idiosyncratic reactions. These have been attributed to the formation of a protein-reactive quinoneimine species via oxidation of the 4-aminophenol group. Therefore, the effects of chemical modifications on the disposition of amodiaquine in relation to its metabolism, distribution, and pharmacological activity have been investigated. The inclusion of a group at the C-5′ position of amodiaquine reduced or elimi...

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

    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.

  17. Combined pharmacological activation of AMPK and PPAR δ potentiates the effects of exercise in trained mice

    Manio, Mark Christian C.; Inoue, Kazuo; Fujitani, Mina; Matsumura, Shigenobu; Fushiki, Tohru

    2016-01-01

    Abstract The combined activation of the cellular energy sensor AMP‐activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator‐activated receptor delta (PPAR δ) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the P...

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

    N.K. Hashilkar; M.H. Gelula

    2014-01-01

    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 KL...

  19. Effective boundary action in fermion string theory

    Continual Polyakov integral for the Neveu-Schwarz-Ramon (NSR) type fermion string is calculated on the Riemann Surface with special choice of local boundary conditions for the fermion fields. The derived expressions are used when studying behaviour of the string Green function in configurational space. Generalization of the effective fermion action for the case of non-Archimedean strings is discussed. 11 refs

  20. Low energy effective actions with composite fields

    We investigate a Wilson real space renormalization gorup approach for theories in which composite fields are needed at low energies. It furnishes a sequence of effective actions SΛ which depend on an UV cut-off Λ. We adopt Wilsons fundamental postulate that these effective actions should be local. This is our basic guiding principle on how to construct ''blockspins'', i.e. the fields which appear in the effective actions. Given a fundamental high energy theory which does not contain composite fields we gradually integrate out high frequency modes in order to lower the cut-off Λ. Eventually appearing nonlocalities at some cut-off value Λc indicate the necessity to introduce new composite degrees of freedom into the theory. An analysis based on Symanzik's infinite set of Bethe-Salpeter equations for all n-point functions shows that a local low energy effective action containing composite fields can be constructed at the compositeness scale Λc. Further integration of high frequency modes generates new nonlocalities which can be absorbed into the composite degrees of freedom. There are indications from an 1/N expansion that this suffices already to eliminate high energy degrees of freedom from the composite field so that no separate integration is needed to achieve this. In general the composite field will have self interactions. (orig.)

  1. Holographic effective actions from black holes

    Using the Wald's relation between the Noether charge of diffeomorphisms and the entropy for a generic spacetime possessing a bifurcation surface, we introduce a method to obtain a family of higher order derivatives effective actions from the entropy of black holes. We consider the entropy as the starting point and we analyze the procedure of derivation of the action functional. We specialize to a particular class of theories which simplifies the calculations, f(R) theories. We apply the procedure to loop quantum gravity and to a general class of log-corrected entropy formulas.

  2. Modafinil and γ-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep

    Zeitzer, Jamie M.; Buckmaster, Christine L.; Landolt, Hans-Peter; David M Lyons; Mignot, Emmanuel

    2009-01-01

    Hypocretin-1 is a hypothalamic neuropeptide that is important in the regulation of wake and the lack of which results in the sleep disorder narcolepsy. Using a monkey that has consolidated wake akin to humans, we examined pharmacological manipulation of sleep and wake and its effects on hypocretin physiology. Monkeys were given the sleep-inducing gamma-hydroxybutyrate (GHB) and the wake-inducing modafinil both in the morning and in the evening. Cerebrospinal fluid (CSF) hypocretin-1 concentra...

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

    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.

  4. Symmetry-improved CJT effective action

    The formalism introduced by Cornwall, Jackiw and Tomboulis (CJT) provides a systematic approach to consistently resumming non-perturbative effects in Quantum Thermal Field Theory. One major limitation of the CJT effective action is that its loopwise expansion introduces residual violations of possible global symmetries, thus giving rise to massive Goldstone bosons in the spontaneously broken phase of the theory. In this paper we develop a novel symmetry-improved CJT formalism for consistently encoding global symmetries in a loopwise expansion. In our formalism, the extremal solutions of the fields and propagators to a loopwise truncated CJT effective action are subject to additional constraints given by the Ward Identities due to global symmetries. By considering a simple O(2) scalar model, we show that, unlike other methods, our approach satisfies a number of important field-theoretic properties. In particular, we find that the Goldstone boson resulting from spontaneous symmetry breaking of O(2) is massless and the phase transition is a second-order one, already in the Hartree–Fock approximation. After taking the sunset diagrams into account, we show how our approach properly describes the threshold properties of the massless Goldstone boson and the Higgs particle in the loops. Finally, assuming minimal modifications to the Hartree–Fock approximated CJT effective action, we calculate the corresponding symmetry-improved CJT effective potential and discuss the conditions for its uniqueness for scalar-field values away from its minimum

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

    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.

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

    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.

  7. 小槐花水提物药理作用研究%Study on Pharmacological Action of Aqueous Extract from Desmodium Caudatum

    李燕婧; 钟正贤; 卢文杰

    2013-01-01

      目的:观察小槐花水提物的药理作用.方法:采用对戊巴比妥钠小鼠睡眠时间的影响实验;小鼠醋酸扭体法;小鼠碳末廓清法和对正常小鼠血清SOD活性和MDA含量的影响实验,以及急性毒性试验.结果:小槐花水提物能明显促进小鼠睡眠并延长其睡眠时间,减少醋酸所致的小鼠扭体反应次数,能提高单核巨噬细胞吞噬指数,降低小鼠血清MDA含量,同时提高SOD活性.小鼠最大给药量为220.5g生药/kg.结论:提示小槐花水提物具有明显的镇静催眠,镇痛,免疫增强和抗氧化作用,且毒性较低.%Objective: To observe the pharmacological action of aqueous extract from Desmodium Caudatum. Methods: The experience was made with pentobarbital-induced hypnosis in mice, the rat's body torsion test, the rat carbo clearance method for Serum SOD and MDA in normal mice and acute toxicity test. Results: Aqueous Extract from Desmodium Caudatum can obviously facilitate sleep, extend sleep time, reduce the body torsion induced by acetic acid, enhance the mononuclear macrophage phagocytic index, reduce the blood serum content of MDA and improve the activity of SOD in mice. The maxi-mum dosage was 220.5 g crude drug/kg. Conclusion: Aqueous Extract from Desmodium Caudatum can provide obvious sedative, hypnotic, analgesia, immune enhancement and antioxygenation effects,with low toxicity.

  8. Cosmic fluctuations from quantum effective action

    Wetterich, C

    2015-01-01

    Does the observable spectrum of cosmic fluctuations depend on detailed initial conditions? This addresses the question if the general inflationary paradigm is sufficient to predict within a given model the spectrum and amplitude of cosmic fluctuations, or if additional particular assumptions about the initial conditions are needed. The answer depends on the number of e-foldings $N_{in}$ between the beginning of inflation and horizon crossing of the observable fluctuations. We discuss an interacting inflaton field in an arbitrary homogeneous and isotropic geometry, employing the quantum effective action $\\Gamma$. An exact time evolution equation for the correlation function involves the second functional derivative $\\Gamma^{(2)}$. The operator formalism and quantum vacua for interacting fields are not needed. Use of the effective action also allows one to address the change of frames by field transformations (field relativity). For not too large $N_{in}$ we find that memory of the initial conditions is preserv...

  9. Effectively Discriminating Fighting Shots in Action Movies

    Shu-Gao Ma; Wei-Qiang Wang

    2011-01-01

    Fighting shots are the highlights of action movies and an effective approach to discriminating fighting shots is very useful for many applications, such as movie trailer construction, movie content filtering, and movie content retrieval. In this paper, we present a novel method for this task. Our approach first extracts the reliable motion information of local invariant features through a robust keypoint tracking computation; then foreground keypoints are distinguished from background keypoints by a sophisticated voting process; further, the parameters of the camera motion model is computed based on the motion information of background keypoints, and this model is then used as a reference to compute the actual motion of foreground keypoints; finally, the corresponding feature vectors are extracted to characterizing the motions of foreground keypoints, and a support vector machine (SVM) classifier is trained based on the extracted feature vectors to discriminate fighting shots. Experimental results on representative action movies show our approach is very effective.

  10. Effective action in general chiral superfield model

    Petrov, A. Yu.

    2000-01-01

    The effective action in general chiral superfield model with arbitrary k\\"{a}hlerian potential $K(\\bar{\\Phi},\\Phi)$ and chiral (holomorphic) potential $W(\\Phi)$ is considered. The one-loop and two-loop contributions to k\\"{a}hlerian effective potential and two-loop (first non-zero) contribution to chiral effective potential are found for arbitrary form of functions $K(\\bar{\\Phi},\\Phi)$ and $W(\\Phi)$. It is found that despite the theory is non-renormalizable in general case two-loop contributi...

  11. Pharmacology in space. Part 2. Controlling motion sickness

    Lathers, C. M.; Charles, J. B.; Bungo, M. W.

    1989-01-01

    In this second article in the two-part series on pharmacology in space, Claire Lathers and colleagues discuss the pharmacology of drugs used to control motion sickness in space and note that the pharmacology of the 'ideal' agent has yet to be worked out. That motion sickness may impair the pharmacological action of a drug by interfering with its absorption and distribution because of alteration of physiology is a problem unique to pharmacology in space. The authors comment on the problem of designing suitable ground-based studies to evaluate the pharmacological effect of drugs to be used in space and discuss the use of salivary samples collected during space flight to allow pharmacokinetic evaluations necessary for non-invasive clinical drug monitoring.

  12. Instant Attraction: Immediate Action-Effect Bindings Occur for Both, Stimulus- and Goal-Driven Actions

    Janczyk, Markus; Heinemann, Alexander; Pfister, Roland

    2012-01-01

    Flexible behavior is only possible if contingencies between own actions and following environmental effects are acquired as quickly as possible; and recent findings indeed point toward an immediate formation of action-effect bindings already after a single coupling of an action and its effect. The present study explored whether these short-term bindings occur for both, stimulus- and goal-driven actions (“forced-choice actions” vs. “free-choice actions”). Two experiments confirmed that immedia...

  13. Ways of pharmacological prophylaxis of stochastic and deterministic effects of chronical radiation exposure

    The prophylactics of late effects of exposure is the actual medico-social problem, because now there are large groups of persons who were exposed during occupational contact and living on territories contaminated by radionuclides. Most probable consequences of external and internal chronic influence of radiation may be the increase of malignant tumour frequency, the development of secondary myelo- and immuno-depressions, the earlier forming of sclerous and destructive processes, and the acceleration of senescence. The role of damages in immune system was not yet understood in pathogenesis of the late effects of radiation, but there are evidences that the decreasing of the immunologic supervision in period of forming the consequences of radiation influence enables to realize the cancerogenic effect of radiation. The purposes of this investigation are to decrease the frequency or to prevent the development of radiation consequences dangerous for health and life by using the method of modification of radiogenic damages in hemopoietic and immune systems by applying the pharmacological preparations with immunomodulating effects. The investigation tasks include: the study of modifying influence of pharmacological substances with different mechanisms of effect: myelopid (immunomodulating, and regulatory), β-carotin, Calendula officinalis (immunomodulating, and antioxidant), lipamid (detoxicating); the separate or complex applications of these substances; and the development of the optimum medico-prophylactic schemes. The advantages of these indicated preparations in comparison with the known (T-activin, thymogen, cytokines, etc.) are the absence of contraindications and the possibility to use per os. (author)

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

    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.

  15. Instant attraction: Immediate action-effect bindings occur for both, stimulus- and goal-driven actions

    MarkusJanczyk

    2012-10-01

    Full Text Available Flexible behavior is only possible if contingencies between own actions and following environmental effects are acquired as quickly as possible; and recent findings indeed point toward an immediate formation of action-effect bindings already after a single coupling of an action and its effect. The present study explored whether these short-term bindings occur for both, stimulus- and goal-driven actions (“forced-choice actions” vs. “free-choice actions”. Two experiments confirmed that immediate action-effect bindings are formed for both types of actions and affect upcoming behavior. These findings support the view that action-effect binding is a ubiquitous phenomenon which occurs for any type of action.

  16. Effective action approach to quantum chromodynamics

    Though the Lagrangian of quantum chromodynamics is well known, it has proven extremely difficult to derive precisely all its consequences to compare with experiment. Approximations based on physical reasoning must be made. One method is to calculate the effective action for some particularly simple configuration of gluons and use this to analyze an arbitrary system of interacting quarks. In the first chapter, the one-loop correction to the gluon propagator is computed in two different ways - dimensional regularization and Schwinger's proper time method. The renormalization mass parameters appearing in the two treatments can then be related and the exact one-loop effective action of a constant gluon field can be expressed in terms of the experimentally determinable Λ/sub MS/. In the following chapter, the interaction of a heavy quark-antiquark pair governed by this action is considered and it is shown how the spectrum, and, in particular, the spin splittings of the bound states can be found. Due to asymptotic freedom, a massive quarkonium is analogous to a non-relativistic electromagnetic system. At short distances, the results are the same as those derived from perturbation theory though, for example, the hyperfine structure arises in a different way. At large distances, the analysis is qualitative but our results agree with the predictions of strong coupling lattice gauge theories

  17. Effective actions for relativistic fluids from holography

    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...

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

    Valérian Chambon; Nura Sidarus

    2014-01-01

    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. Accordi...

  19. Cosmic fluctuations from a quantum effective action

    Wetterich, C.

    2015-10-01

    Does the observable spectrum of cosmic fluctuations depend on detailed initial conditions? This addresses the question if the general inflationary paradigm is sufficient to predict within a given model the spectrum and amplitude of cosmic fluctuations, or if additional particular assumptions about the initial conditions are needed. The answer depends on the number of e -foldings Nin between the beginning of inflation and horizon crossing of the observable fluctuations. We discuss an interacting inflaton field in an arbitrary homogeneous and isotropic geometry, employing the quantum effective action Γ . An exact time evolution equation for the correlation function involves the second functional derivative Γ(2 ) . The operator formalism and quantum vacua for interacting fields are not needed. Use of the effective action also allows one to address the change of frames by field transformations (field relativity). Within the approximation of a derivative expansion for the effective action we find the most general solution for the correlation function, including mixed quantum states. For not too large Nin the memory of the initial conditions is preserved. In this case the cosmic microwave background cannot disentangle between the initial spectrum and its processing at horizon crossing. The inflaton potential cannot be reconstructed without assumptions about the initial state of the universe. We argue that for very large Nin a universal scaling form of the correlation function is reached for the range of observable modes. This can be due to symmetrization and equilibration effects, not yet contained in our approximation, which drive the short distance tail of the correlation function toward the Lorentz invariant propagator in flat space.

  20. Understanding Medicines: Conceptual Analysis of Nurses' Needs for Knowledge and Understanding of Pharmacology (Part I). Understanding Medicines: Extending Pharmacology Education for Dependent and Independent Prescribing (Part II).

    Leathard, Helen L.

    2001-01-01

    Part I reviews what nurses need to know about the administration and prescription of medicines. Part II addresses drug classifications, actions and effects, and interactions. Also discussed are the challenges pharmacological issues pose for nursing education. (SK)

  1. Effective actions for statistical data assimilation

    Data assimilation is a problem in estimating the fixed parameters and state of a model of an observed dynamical system as it receives inputs from measurements passing information to the model. Using methods developed in statistical physics, we present effective actions and equations of motion for the mean orbits associated with the temporal development of a dynamical model when it has errors, there is uncertainty in its initial state, and it receives information from noisy measurements. If there are statistical dependences among errors in the measurements they can be included in this approach.

  2. Effective action of domain wall networks

    U(NC) gauge theory with NF fundamental scalars admits BPS junctions of domain walls. When the networks/webs of these walls contain loops, their size moduli give localized massless modes. We construct Kaehler potential of their effective action. In the large size limit Kaehler metric is well approximated by kinetic energy of walls and junctions, which is understood in terms of tropical geometry. Kaehler potential can be expressed in terms of hypergeometric functions that are useful to understand small size behavior. Even when the loop shrinks, the metric is regular with positive curvature. Moduli space of a single triangle loop has a geometry between a cone and a cigar

  3. Effective action calculation in lattice QCD

    A method (called the effective action method) devised to make analytic calculations in Quantum Chromodynamics in the region of strong coupling is presented. First, the author deals with developing the calculation of a strong coupling expansion of the generating functional for gauge systems on a lattice with arbitrary sources. An accompanying manual describes the implementation of this calculation on a computer. The next step consists of substituting the expressions for the one-link free energies for a specific gauge group in the result of the previous calculation. This process of substitution, together with the replacement of the sources by a bilinear combination of fermion fields, is described for the group SU(3). More details on the implementation of the substitution scheme on a computer can be found in the accompanying manual. From the effective action thus obtained in terms of meson fields and baryon fields the Green functions of the theory can be derived. As an illustrative application the effective potential determining the vacuum expectation value of the meson field is calculated. (Auth.)

  4. Studies in neuroendocrine pharmacology

    Maickel, R. P.

    1976-01-01

    The expertise and facilities available within the Medical Sciences Program section on Pharmacology were used along with informational input from various NASA sources to study areas relevant to the manned space effort. Topics discussed include effects of drugs on deprivation-induced fluid consumption, brain biogenic amines, biochemical responses to stressful stimuli, biochemical and behavioral pharmacology of amphetamines, biochemical and pharmacological studies of analogues to biologically active indole compounds, chemical pharmacology: drug metabolism and disposition, toxicology, and chemical methodology. Appendices include a bibliography, and papers submitted for publication or already published.

  5. The ventral surface of the medulla in the rat: pharmacologic and autoradiographic localization of GABA-induced cardiovascular effects.

    Keeler, J R; Shults, C W; Chase, T N; Helke, C J

    1984-04-16

    Experiments were done to evaluate a rat model for studying the cardiovascular effects of pharmacological manipulations of the ventral surface of the medulla. GABAergic drugs were used because of their well-characterized actions at the ventral surface of the medulla in the cat. GABA and muscimol, applied to the exposed ventral surface with filter paper pledgets, produced dose-dependent decreases in heart rate (HR) and mean arterial pressure (MAP) which were reversed with bicuculline but not with strychnine. Bicuculline alone raised HR and MAP. The GABA- or bicuculline-induced cardiovascular effects were mediated primarily by inhibition of sympathetic outflow. The most sensitive site was localized to an intermediate area on the ventral surface of the medulla, between the trapezoid body and exits of the hypoglossal nerves and just lateral to the pyramids. Topical application of [3H]GABA to the intermediate area resulted in labeling that was concentrated at the site of application, and which penetrated the parenchyma 1 mm dorsally. The heaviest labeling was found primarily in the ventral halves of the lateral paragigantocellular nuclei. No tritium was detected in peripheral blood. These data provide evidence for a neuronal system at the ventral medullary surface of the rat which influences sympathetic outflow and is modulated by GABA. PMID:6326937

  6. Exploring soft constraints on effective actions

    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...

  7. Prenatal manipulation of the serotonergic system: Biochemical, pharmacological and behavioral effects

    Rat pups were exposed in utero to pharmacological agents that stimulated or diminished serotonergic activity in vivo. Dams received 5-Methoxytryptamine 1mg/kg, from day 12 of gestation to birth, or parachlorophenylalanine, the serotonin synthesis inhibitor, from day 7 to 17 of gestation. Both groups of offspring showed significant reductions in the specific high affinity uptake of 3H-5-HT into brainstem and forebrain areas on postnatal days 1, 15, and 30, indicating reduced outgrowth of serotonin. At 15 days of age, both groups of treated offspring showed deficits in activity and in performing behaviors that required inhibition, but these deficits were no longer apparent on Day 30. Dose response experiments for 5-MT produced a dual effect: enhanced uptake in forebrain and inhibition of uptake in brainstem and forebrain on postnatal days 1, 15 and 30. Prenatal 5-MT caused deficits in avoidance and activity. Prenatal exposure to PAT, the 5-HT1a agonist caused reduced uptake in brainstem, while exposure to TFMPP (the 5-HT1b agonist) produced enhanced uptake in forebrain, as did the high dose of 5-MT. Sensitivity of the pharmacological response to acute 5-MT, 1 mg/kg, and apomorphine, 5 mg/kg was measured in an activity test

  8. Prenatal manipulation of the serotonergic system: Biochemical, pharmacological and behavioral effects

    Shemer, A.V.

    1988-01-01

    Rat pups were exposed in utero to pharmacological agents that stimulated or diminished serotonergic activity in vivo. Dams received 5-Methoxytryptamine 1mg/kg, from day 12 of gestation to birth, or parachlorophenylalanine, the serotonin synthesis inhibitor, from day 7 to 17 of gestation. Both groups of offspring showed significant reductions in the specific high affinity uptake of {sup 3}H-5-HT into brainstem and forebrain areas on postnatal days 1, 15, and 30, indicating reduced outgrowth of serotonin. At 15 days of age, both groups of treated offspring showed deficits in activity and in performing behaviors that required inhibition, but these deficits were no longer apparent on Day 30. Dose response experiments for 5-MT produced a dual effect: enhanced uptake in forebrain and inhibition of uptake in brainstem and forebrain on postnatal days 1, 15 and 30. Prenatal 5-MT caused deficits in avoidance and activity. Prenatal exposure to PAT, the 5-HT{sub 1a} agonist caused reduced uptake in brainstem, while exposure to TFMPP (the 5-HT{sub 1b} agonist) produced enhanced uptake in forebrain, as did the high dose of 5-MT. Sensitivity of the pharmacological response to acute 5-MT, 1 mg/kg, and apomorphine, 5 mg/kg was measured in an activity test.

  9. Effects of modified pharmacologic stress approaches on hyperemic myocardial blood flow

    Czernin, J.; Auerbach, M.; Sun, K.T. [Univ. of California, Los Angeles, CA (United States)] [and others

    1995-04-01

    Pharmacologic stress testing with 0.56 mg/kg of intravenous dipyridamole is frequently used to noninvasively detect coronary artery disease (CAD). However, high-dose dipyridamole (0.80 mg/kg) or the combination of standard-dose dipyridamole (0.56 mg/kg) with the isometric handgrip maneuver might evoke a greater coronary hyperemic response. To evaluate the effect of modified pharmacologic stress tests, myocardial blood flow was quantified in 11 male subjects (mean age: 27 {plus_minus} 7 yr) during standard-dose dipyridamole (0.56 mg/kg), high-dose dipyridamole (0.80 mg/kg) and standard-dose dipyridamole combined with the isometric handgrip exercise using dynamic PET and a two-compartment model for {sup 13}N-ammonia. Systolic blood pressure, heart rate and rate pressure product remained unchanged from standard to high-dose dipyridamole but increased with the addition of the isometric handgrip. Myocardial blood flow was unchanged from standard to high-dose dipyridamole but was lower with the addition of the isometric handgrip. The hyperemic response induced by standard-dose dipyridamole cannot be further enhanced by high-dose dipyridamole. The addition of the isometric handgrip exercise results in a modest, but significant decline in hyperemic blood flow possibly due to increased extravascular resistive forces or an increase in a mediated coronary vasoconstriction associated with exercise. 31 refs., 2 figs., 1 tab.

  10. 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

    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。

  11. 姜黄素药理作用及其机制研究进展%Research progress of curcumin pharmacological action and mechanism

    刘红艳; 王海燕; 叶松

    2012-01-01

    Curcumin is a phenolic pigment of the ginger family Curcuma root-Curcuma longa L, it is the effective drug monomer. Turmeric is a commonly used traditional Chinese medicine, mainly growing in Japan, the United States, Africa, China and so on. Pharmacological studies suggest, curcumin possesses anti-inflammatory, antioxidant, anticoagulation, hypolipidemic, scavenging free radicals, atherosclerosis and inhibits tumor growth in many aspects such as the function, diseases of the cardiovascular system also has a certain role. This paper discusses the pharmacological effect of curcumin and its clinical application.%姜黄素是一种从姜黄提取的酚类色素,有效的药物单体.药理研究表明,姜黄素具有抗炎、抗凝、降血脂、抗氧化、清除自由基、抗动脉粥样硬化及抑制肿瘤生长等多方面的功能,对心血管系统疾病也有一定的作用.本文讨论了姜黄素的药理作用及临床应用.

  12. The Universal One-Loop Effective Action

    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.

  13. The universal one-loop effective action

    Drozd, Aleksandra; Ellis, John; Quevillon, Jérémie; You, Tevong

    2016-03-01

    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.

  14. The effective action for composite Higgs particles

    There is reason to believe that massive composite (fermion-antifermion) scalar particles closely resembling the usual fundamental scalar Higgs fields exist in theories with dynamically broken gauge symmetries. This composite Higgs couples directly to the fermions in proportion to their symmetry-violating self-energies. Induced couplings to the gauge bosons and self-couplings are claculated as loop effects. This involves deriving the effective action in terms of the full propagators and background fields. The couplings between the composite Higgs and the gauge bosons are the same as those in models with fundamental scalars. The self-couplings are determined and fix all parameters associated with the composite scalars. Comments regarding extending work to higher orders and concerning the symmetry-violating solutions to the fermion Schwinger-Dyson equation are given in this paper

  15. Curriculum Guidelines for Pharmacology.

    Shaw, David H.; And Others

    1990-01-01

    Pharmacology embraces the physical and chemical properties of drugs; the preparation of pharmaceutical agents; the absorption, fate, and excretion of drugs; and the effects of drugs on living systems. These guidelines represent a consensus on what would constitute a minimally acceptable pharmacology course for predoctoral dental students. (MLW)

  16. Action-based effects on music perception

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

    2014-01-01

    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 cornerst...

  17. Action-based effects on music perception

    Pieter-Jan eMaes; Marc eLeman; Caroline ePalmer; Marcelo eWanderley

    2014-01-01

    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 co...

  18. Effective Action of Domain Wall Networks

    Eto, M; Nagashima, T; Nitta, M; Ohashi, K; Sakai, N; Eto, Minoru; Fujimori, Toshiaki; Nagashima, Takayuki; Nitta, Muneto; Ohashi, Keisuke; Sakai, Norisuke

    2007-01-01

    U(Nc) gauge theory with Nf fundamental scalars admits BPS junctions of domain walls. When the networks/webs of these walls contain loops, their size moduli give localized massless modes. We construct K\\"ahler potential of their effective action. In the large size limit K\\"ahler metric is well approximated by kinetic energy of walls and junctions, which is understood in terms of tropical geometry. K\\"ahler potential can be expressed in terms of hypergeometric functions which are useful to understand small size behavior. Even when the loop shrinks, the metric is regular with positive curvature. Moduli space of a single triangle loop has a geometry between a cone and a cigar.

  19. Boundary Effective Action for Quantum Hall States

    Gromov, Andrey; Jensen, Kristan; Abanov, Alexander G.

    2016-03-01

    We consider quantum Hall states on a space with boundary, focusing on the aspects of the edge physics which are completely determined by the symmetries of the problem. There are four distinct terms of Chern-Simons type that appear in the low-energy effective action of the state. Two of these protect gapless edge modes. They describe Hall conductance and, with some provisions, thermal Hall conductance. The remaining two, including the Wen-Zee term, which contributes to the Hall viscosity, do not protect gapless edge modes but are instead related to the local boundary response fixed by symmetries. We highlight some basic features of this response. It follows that the coefficient of the Wen-Zee term can change across an interface without closing a gap or breaking a symmetry.

  20. Pharmacological and clinical properties of curcumin

    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

  1. Pharmacological actions of Uncaria alkaloids,rhynchophylline and isorhynchophylline%钩藤总碱、钩藤碱和异钩藤碱的药理作用

    石京山; 余俊先; 陈修平; 徐瑞霞

    2003-01-01

    The pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline extracted from Uncaria rhynchophylla Miq Jacks were reviewed. The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension, brachycardia, antiarrhythmia, and protection of cerebral ischemia and sedation.The active mechanisms were related to blocking of calcium channel, opening of potassium channel,and regulating of nerve transmitters transport and metabolism,etc.%综述了钩藤总碱、钩藤碱和异钩藤碱对心血管系统和神经系统等方面的药理作用,包括降低血压、减慢心率、抗心律失常、脑缺血保护,以及镇静等作用,其作用机制与钙通道阻滞、钾通道开放、以及神经递质转运和代谢的调节有关.

  2. Methamphetamine exposure during pregnancy at pharmacological doses produces neurodevelopmental and behavioural effects in rat offspring.

    McDonnell-Dowling, Kate; Donlon, Michelle; Kelly, John P

    2014-06-01

    In recent years methamphetamine (MA) use has become more prevalent, and of particular concern is its growing popularity of MA among women of childbearing age. However, to date, studies examining MA effects on the developing offspring in laboratory animals are limited. Thus, the aim of this study was to determine if in utero MA exposure in rats at pharmacological doses can have a negative impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral gavage from gestational day 7 to 21. Maternal body weight, food and water consumption were recorded daily. A range of standard neurodevelopment parameters was examined in the offspring during the neonatal period. There were no neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in fact, there were enhancements of neurodevelopment in some parameters at this low dose. However, exposure to the 1.25mg/kg MA dose resulted in significant impairments in surface righting reflex and forelimb grip in both sexes. Exposure to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital distance in males, and in both sexes resulted in delayed fur appearance and eye opening, impairments in surface righting reflex and negative geotaxis, and a reduction in body length. In conclusion, this study demonstrates that pharmacologically relevant doses of MA can have profound dose-related effects on neonatal outcome. If extrapolated to the clinical scenario this will give cause for concern regarding the risks associated with this drug of abuse at relatively low doses. PMID:24667147

  3. Perception of actions performed by external agents presupposes knowledge about the relationship between action and effect.

    Raos, Vassilis; Savaki, Helen E

    2016-05-15

    We used the (14)C-deoxyglucose method to reveal changes in activity, in the lateral sulcus of monkeys, elicited by reaching-to-grasp in the light or in the dark and by observation of the same action executed by an external agent. Both visually-guided execution and observation of the same action activated the secondary somatosensory cortex, the ventral somatosensory area, the somatorecipient parietal ventral area, the retroinsula and the caudo-medial area of the auditory belt. These matching activations indicate that the somesthetic consequences of movements, generated bottom-up during action execution, may also be triggered top-down during action observation to represent the predicted sensory consequences of the perceived movement. The posterior granular part of insula found to be activated only for action execution and its anterior agranular part activated only for action observation may contribute to the attribution of action to the correct agent. Also, execution in the dark implicated all components activated by execution in the light but the retroinsula. In conclusion, activation of the somatorecipient parietal areas, not only for action-execution but also for action-observation, indicates that perception of actions performed by an external agent presupposes knowledge about the action-effect relationships, and that understanding others' actions consists of running off-line previously stored sensory-motor programs. PMID:26892857

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

    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

  5. Pharmacological Actions of NGB 2904, a Selective Dopamine D3 Receptor Antagonist, in Animal Models of Drug Addiction

    Xi, Zheng-Xiong; Gardner, Eliot L

    2007-01-01

    As a continuation of our work with SB-277011A, we have examined the effects of another highly elective dopamine (DA) D3 receptor antagonist, N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904), in animal models of addiction. Our results indicate that by systemic administration, NGB 2904 inhibits intravenous cocaine self-administration maintained under a progressive-ratio (PR) reinforcement schedule, cocaine-or cocaine cue–induced reinstatement of cocaine-seekin...

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

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

    2011-07-01

    Full Text Available 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 & 7.5 mg/kg respectively while, that of the native venom was (0.39 mg/kg. Moreover, the distribution of 125I-labeled L.q venom was studied in male Swiss mice tissue using chloramine-T method by being injected intravenously. At various time intervals, urine and blood were collected and the animals were sacrificed. Brain, lungs, heart, liver, kidneys, spleen, intestine, bone and muscle were isolated in order to determine the radioactivity content. The highest contents of 125I-labeled L.q venom were found in the liver and kidney that were quickly excreted into the urinary tract. Trial to label irradiated (1.5 & 3 KGy L.q venom was unsuccessful due to its decomposition. For that reason the utilization of the labeled irradiated L.q venom is of no meaning. In immunodiffusion technique, both irradiated and native venoms exhibited prominent precipitin bands indicating high concentration of specific antibodies against polyvalent antivenin with venom. Furthermore, the effect of half the LD50 of native or irradiated (1.5 KGy L.q venom was studied on the activities of certain enzymes: ASAT, ALAT, LDH, CPK, CPK-MB, and the levels of total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol and the oxidative stress biomarkers (plasma MDA & blood GSH. Biochemical measurements showed that scorpion venom envenomation caused significant (p < 0.05 elevation in serum ASAT, ALAT, LDH, CPK as well as CPK-MB activities, blood GSH level while, caused significant (p < 0

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

    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 ...

  8. Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

    Kang, Jung-Woo; Yun, Nari; Han, Hae-Jung; Kim, Jeom-Yong; Kim, Joo-Young; Lee, Sun-Mee

    2014-01-01

    Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101) on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and ...

  9. Gaultheria: Phytochemical and pharmacological characteristics.

    Liu, Wei-Rui; Qiao, Wen-Lin; Liu, Zi-Zhen; Wang, Xiao-Hong; Jiang, Rui; Li, Shu-Yi; Shi, Ren-Bing; She, Gai-Mei

    2013-01-01

    The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C₆-C₃ constituents, organic acids, terpenoids, steroids, and other compounds. Methyl salicylate glycoside is considered as a characteristic ingredient in this genus, whose anti-rheumatic effects may have a new mechanism of action. In this review, comprehensive information on the phytochemistry, volatile components and the pharmacology of the genus Gaultheria is provided to explore its potential and advance research. PMID:24084015

  10. Gaultheria: Phytochemical and Pharmacological Characteristics

    Ren-Bing Shi

    2013-09-01

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

  11. The role of action effects in 12-month-olds' action control: a comparison of televised model and live model.

    Klein, Annette M; Hauf, Petra; Aschersleben, Gisa

    2006-12-01

    The present study investigated differences in infant imitation after watching a televised model and a live model and addressed the issue of whether action effects influence infants' action control in both cases. In a 2x2 design, 12-month-old infants observed a live or a televised model performing a three-step action sequence, in which either the 2nd or the 3rd action step was combined with an acoustical action effect. We assumed that infants would use the observed action-effect relations for their own action control in the test phase afterwards. Even though results exhibited differences in the absolute amount of imitation between the two demonstration groups, both groups showed similar result patterns regarding the action effect manipulation: infants imitated the action step that was followed by a salient action effect more often and mostly as the first target action, emphasizing the important role of action effects in infants' action control. PMID:17138306

  12. Combined pharmacological activation of AMPK and PPARδ potentiates the effects of exercise in trained mice.

    Manio, Mark Christian C; Inoue, Kazuo; Fujitani, Mina; Matsumura, Shigenobu; Fushiki, Tohru

    2016-03-01

    The combined activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator-activated receptor delta (PPARδ) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks. AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively). Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion. Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression. Citrate synthase activity was elevated in AICAR-treated groups, while PGC-1α protein level tended to be increased in GW0742-treated groups. At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle. A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver. Our data show that combined pharmacological activation of AMPK and PPARδ potentiates endurance in trained mice by transcriptional changes in muscle and liver, increased available energy substrates, delayed hypoglycemia through glycogen sparing accompanied by increased NEFA availability, and improved substrate shift from carbohydrate to fat. PMID:26997622

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

    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.

  14. 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

    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.

  15. Chemical constituents and pharmacologic actions of Cynomorium plants%锁阳属植物的化学成分及药理作用

    蒙昊聪; 王硕; 李颖; 况园园; 马超美

    2013-01-01

    锁阳是锁阳科植物Cynomorium songaricum的根茎,是以具有强壮作用而著名的中药材.生长在北非及地中海地区的同属植物C coccineum被阿拉伯人看作是“宝药”.研究表明锁阳属植物的主要成分为酚类、甾体和三萜类化合物等.锁阳属植物的药理作用包括抗氧化、提高免疫力、抗糖尿病及神经保护等.锁阳的一些化学成分结构容易发生变化,因此不同生产条件得到的锁阳类药物成分会有所不同.该文综述锁阳属植物的药理作用及化学成分,检索的文献截至2011年底.%The stem of Cynomorium songaricum is a traditional Chinese medicine reputed to have tonic effects.C.coccineum growing in northern Africa and the Mediterranean region is regarded in Arabian medical practice as the "treasure of drugs".The major constituents of Cynomorium plants have been revealed to be phenolic compounds,steroids,triterpenes,etc.Pharmacologic studies showed that the Cynomorium plants had antioxidant,immunity-improving,anti-diabetic,neuroprotective,and other bioactivities.Some chemical constituents in Cynomorium plants are unstable,implying that the chemical components of the herbal medicines produced under different conditions may be variable.This review covers the literature published until December,2011 and describes the pharmacologic effects and secondary metabolites of Cynomorium species.

  16. The effective action in four-dimensional CDT

    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. [Pharmacology of bone resorption inhibitor].

    Menuki, Kunitaka; Sakai, Akinori

    2015-10-01

    Currently, bone resorption inhibitor is mainly used for osteoporosis. A number of these agents have been developed. These pharmacological action are various. Bisphosphonate inhibit functions of the osteoclasts by inducing apoptosis. On the one hand, RANK-ligand inhibitor and selective estrogen receptor modulator inhibit formation of osteoclasts. It is important to understand these pharmacological action for the selection of the appropriate medicine. PMID:26529923

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

    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

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

    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

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

    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

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

    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. PMID:23212430

  2. STUDENTS’ ATTITUDE TOWARDS DIFFERENT EVALUATION METHODS IN PHARMACOLOGY

    Majagi Suneel Ishwar

    2012-08-01

    Full Text Available Literature review suggests the importance and the need of students’ feedback which may be used to effectively reform evaluation methods in medical sciences. The present study has been conducted to obtain student’s attitude (perception of towards different evaluation methods of pharmacology. The sample consisted of second phase M.B.B.S (n=108 students. Students answered 115 items/questions designed according to Likert’s five point (in agreement with items scale. These items/questions assessed student’s attitude (perception of towards different constituents of evaluation methods of pharmacology like sessional exams, traditional practical exams, objective structured practical exam (OSPE, MCQs, long essays, viva voce, pharmacy practical exercise, experimental pharmacology exercise etc in relation with various aspects of pharmacology subject like understanding, retention, learning clinical applications, mechanism of action of drugs, pharmacological actions, therapeutic uses, prescribing drugs etc. Results of the present study indicated the degree to which each evaluation method like sessional/preliminary theory exams, traditional practical exams and OSPE helps to elicit different constituents of pharmacology subject (ex: mechanism of action of drugs, therapeutic uses etc and the reason for the same is discussed. Similarly usefulness of different constituents of theory exams (MCQs, long essay etc and practical exams (spotters, pharmacy exercises etc towards eliciting the understanding pharmacology is revealed. Present study indicated the merits and demerits of different evaluation methods used in pharmacology. If any reformations/changes have to be incorporated in the evaluation methods, outcomes of this study will definitely help towards improving/modifying the evaluation methods of teaching and learning of pharmacology subject.

  3. Pharmacological Action of Adenophora Polysaccharides

    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.

  4. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

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

    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. PMID:24295631

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

    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

  7. 热毒宁注射液的药理作用、临床应用及不良反应分析%Toxic heat ning injection pharmacological action, clinical application and adverse reactions

    黄克冬

    2015-01-01

    Objective To toxic heat ning injection pharmacological action, clinical application and adverse reactions to contrast analysis. Methods The 86 patients treated by toxic heat ning injection on research and analysis, to analyze its clinical effects, pharmacological effects and adverse reactions. Results This study selected patients, the clinical total effective rate was 98.48%in patients with acute upper respiratory tract infection, viral pneumonia in patients with clinical treatment the total effective rate was 92.86%, rotavirus viral enteritis patients clinical total effective rate was 83.33%; The incidence of adverse reactions was 4.65%, allergy 2 cases,blood in the urine 1 case,damage to the skin and attachment 1 case , but no serious adverse reactions such as anaphylactic shock and acute laryngeal edema. Conclusion Patients with toxic heat ning injection used in the treatment effect is signiifcant, and less adverse reaction, improve the prognosis of patients.%目的:对热毒宁注射液的药理作用、临床应用及不良反应展开分析。方法对通过热毒宁注射液治疗的患者86例进行研究分析,分析其疗效、药理作用和出现的不良反应。结果本次研究选取患者中,急性上呼吸道感染患者治疗总有效率为98.48%,病毒性肺炎患者治疗总有效率为92.86%,轮状病毒性肠炎患者治疗总有效率为83.33%;不良反应发生率为4.65%,过敏2例,血尿1例,皮肤和附件损害1例,但均没有出现过敏性休克和急性喉头水肿等严重不良反应。结论患者在采用热毒宁注射液治疗时疗效较为显著,且出现的不良反应较少,改善患者预后。

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

    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

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

    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

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

    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.

  11. Effects of streptozotocin-induced diabetes on the pharmacology of rat conduit and resistance intrapulmonary arteries

    Howarth Frank C

    2009-01-01

    Full Text Available Abstract Background Poor control of blood glucose in diabetes is known to promote vascular dysfunction and hypertension. Diabetes was recently shown to be linked to an increased prevalence of pulmonary hypertension. The aim of this study was to determine how the pharmacological reactivity of intrapulmonary arteries is altered in a rat model of diabetes. Methods Diabetes was induced in rats by the β-cell toxin, streptozotocin (STZ, 60 mg/kg, and isolated conduit and resistance intrapulmonary arteries studied 3–4 months later. Isometric tension responses to the vasoconstrictors phenylephrine, serotonin and PGF2α, and the vasodilators carbachol and glyceryl trinitrate, were compared in STZ-treated rats and age-matched controls. Results STZ-induced diabetes significantly blunted the maximum response of conduit, but not resistance pulmonary arteries to phenylephrine and serotonin, without a change in pEC50. Agonist responses were differentially reduced, with serotonin (46% smaller affected more than phenylephrine (32% smaller and responses to PGF2α unaltered. Vasoconstriction caused by K+-induced depolarisation remained normal in diabetic rats. Endothelium-dependent dilation to carbachol and endothelium-independent dilation to glyceryl trinitrate were also unaffected. Conclusion The small resistance pulmonary arteries are relatively resistant to STZ-induced diabetes. The impaired constrictor responsiveness of conduit vessels was agonist dependent, suggesting possible loss of receptor expression or function. The observed effects cannot account for pulmonary hypertension in diabetes, rather the impaired reactivity to vasoconstrictors would counteract the development of pulmonary hypertensive disease.

  12. Comparative study of native and irradiated crotoxin. Biochemical and pharmacological effects

    Ionizing radiation is able to detoxify several venoms, including snake venom, without affecting significantly their antigenic and immunogenic properties. In order to elucidate this phenomena, we conceived a comparative biochemical and pharmacological study between native and gamma irradiated (2000Gy) crotoxin, main toxin of south american rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified from crude venom by molecular exclusion chromatography, pI precipitation and then irradiated. Immunodiffusion, electrophoresis and gel filtration showed that the molecular integrity was preserved after irradiation with some higher molecular weight aggregate formation and maintenance of its antigenic capacity. The antibodies induced by irradiated toxin had a similar titer to the antibodies induced by native crotoxin; however with higher protective effects in mice. Crotoxin toxicity became 15 times lower after irradiation, as determined by LD sub(50) in mice. Native and irradiated crotoxin biodistribution occurred with a similar general pattern, with renal elimination. In contrast to irradiated crotoxin, the native crotoxin is initially retained in kidneys. A later concentration (2-3hs) occurs in phagocyticmononuclear cells rich organs (liver and spleen) and neural junctions rich organs (muscle and brain). (author)

  13. Faddeev-Niemi Conjecture and Effective Action of QCD

    Cho, Y. M.; Lee, H. W.; Pak, D. G.

    2001-01-01

    We calculate a one loop effective action of SU(2) QCD in the presence of the monopole background, and find a possible connection between the resulting QCD effective action and a generalized Skyrme-Faddeev action of the non-linear sigma model. The result is obtained using the gauge-independent decomposotion of the gauge potential into the topological degrees which describes the non-Abelian monopoles and the local dynamical degrees of the potential, and integrating out all the dynamical degrees...

  14. Statistics in Pharmacology

    Spina, D.

    2007-01-01

    Statistics is an important tool in pharmacological research that is used to summarize (descriptive statistics) experimental data in terms of central tendency (mean or median) and variance (standard deviation, standard error of the mean, confidence interval or range) but more importantly it enables us to conduct hypothesis testing. This is of particular importance when attempting to determine whether the pharmacological effect of one drug is superior to another which clearly has implications f...

  15. Pharmacology of cannabinoids.

    Grotenhermen, Franjo

    2004-01-01

    Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several countries. The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. PMID:15159677

  16. Effective action for supersymmetrical chiral anomaly

    It is proved that the consistency conditions of the type of Wess-Zumino conditions are necessary and sufficient for local integrability of supersymmetrical chiral anomaly. The global integrability condition implies discreteness of the coefficient in anomalous action. Explicit formulas for consistent anomalies and corresponding functional depending on superfields of various types are obtained

  17. Conformally covariant operators and effective action in external gravitational field

    The n-dimensional expressions for the second order conformally covariant differentional operators acting on vector and tensor fields and for the fourth order conformally covariant operator acting on scalar fields are obtained. For the fourth order operator one-loop effective action is evaluated in four dimensions. The possibility of effective action evaluation for other conformally covariant operators is discussed

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

    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.

  19. Pharmacological effects of Eugenia uniflora (Myrtaceae) aqueous crude extract on rat's heart.

    Consolini, Alicia E; Sarubbio, Marisol Gracía

    2002-06-01

    The effect of aqueous crude extract (ACE) of Eugenia uniflora L. (Myrtaceae) was studied on rat's perfused ventricles. This plant is used in South American traditional medicine as an antihypertensive and we already demonstrated previously its hypotensive properties. In this paper, maximal left intraventriclular pressure (P) of rat's hearts beating at 0.2 Hz firstly increased to 162.1+/-11.1% of basal value during 1-3 min of perfusing ACE 0.6%. Maximum rate of contraction (+P) also increased to duplicating +P/P ratio. Both types of effect were significantly decreased by either propranolol 0.35 microM, and pre-treatment with reserpine (5 mg/kg), suggesting that they were caused by a compound that releases cathecolamines with beta-adrenergic action. Nevertheless, after 20 min of perfusing ACE, ventricles decreased P to about 50% of their basal value, suggesting a negative-inotropic compound present in the extract. The perfusion of 1.2% ACE decreased P in a pressure-[Ca](o) curve (0.5-2 mM) in a non-competitive manner, suggesting that an irreversible Ca-blocking compound is also present in the extract. In summary, E. uniflora ACE has a dual effect on the heart related to its hypotensive action and is probably responsible for the therapeutic or adverse effects in patients under cardiac risk. PMID:12020928

  20. Review on the Research of the Components, Pharmacological Actions and Toxicity of Polygonum Multiflorum Thunb(Heshouwu)%何首乌成分、药理及毒副作用相关的研究进展

    楼招欢; 吕圭源; 俞静静

    2014-01-01

    [Objective] To sum up researches on components, pharmacological actions and toxicity of Polygonum multiflorum Thunb(Heshouwu). [Method] The research reference about Heshouwu in CNKI, VIP and PUBMAD database is col ected and calssified to three aspects on components, pharmacological actions and toxicity.[Result]①On components:Heshouwu contains stilbene, lecithin, anthraquinone, flavonoids, tannin and trace elements. The stilbene and anthraquinone are the mainly active components. Producing area, growth years, harvest time and processing methods are factors affecting the content of the components such as TSG in Heshouwu; Macroporous adsorption resin is the main separation method for preconcentration of TSG and anthraquinone constituents; ② On pharmacological actions and toxicity: Heshouwu has effects of hypolipidemic and liver protection, antioxidative, anti-osteoporosi, hpyerglycemic, antidepressive and antibiosis, the hypolipidemic and liver protection are the main effects which have been studied more. A reversible liver injury which displays as abnormal liver function parameter and bile metabolic disorder would be induced if the Heshouwu is administrated with a large dosage for long term. The possible components which would induce the toxicity in Heshouwu are tannin and anthraquinone, and the anthraquinone is the component with double effects of toxicity and therapy which should be considered in clinical application. [Conclusion]Reducing lipid and protecting liver is the main pharmaceutical function of the herb. As a commonly used Chinese herb for liver protection, the studies on alcoholic hepatic injury protection of Heshouwu may be a point for the researchers to focus on. The comparison studies on hypolipidemic and liver protection between Hesouwu and its processing products, and the correlations between components and pharmacological actions are worth study further.%[目的]总结何首乌在成分、药理和毒副作用方面的研究情况。[方法]查

  1. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances

    Trnovec, T.; Kallay, Z.; Bezek, S. (Institute of Experimental Pharmacology, Bratislava (Yugoslavia))

    1990-12-01

    Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultrastructural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. 68 references.

  2. Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness.

    Chacon-Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro J; Mateu-Jimenez, Mercè; Diament, Miriam J; de Kier Joffé, Elisa D Bal; Sandri, Marco; Barreiro, Esther

    2014-11-01

    Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-κB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-κB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-κB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-κB and MAPK, but not the proteasome system, induced in cancer cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. Attenuation of MAPK and NF-κB signaling pathway effects on muscles is beneficial in cancer-induced cachexia. PMID:24615622

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

    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.

  4. 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

    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)

  5. 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

    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.

  6. Assessment of Acute and Chronic Pharmacological Effects on Energy Expenditure and Macronutrient Oxidation in Humans: Responses to Ephedrine

    Derek J. R. Nunez; Steve O'Rahilly; Peter R. Murgatroyd; Nick Finer; Hussey, Elizabeth K.; Robert Dobbins; Antonella Napolitano

    2010-01-01

    Evidence of active brown adipose tissue in human adults suggests that this may become a pharmacological target to induce negative energy balance. We have explored whole-body indirect calorimetry to detect the metabolic effects of thermogenic drugs through administration of ephedrine hydrochloride and have assessed ephedrine's merits as a comparator compound in the evaluation of novel thermogenic agents. Volunteers randomly given ephedrine hydrochloride 15 mg QID (n = 8) or placebo (n = 6) wer...

  7. A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain

    Kuijpers, T; van Middelkoop, M.; Rubinstein, S.M.; Ostelo, R.; Verhagen, A.; Koes, B W; van Tulder, M. W

    2010-01-01

    The objective of this review was to determine the effectiveness of pharmacological interventions [i.e., non-steroid anti-inflammatory drugs (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions were screened for studies fulfilling the inclusion criteria. Then, the literature searches were updated. Only randomized controlled trials on adults (≥18 years) with chronic (≥12 weeks) non-specific L...

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

    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...

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

    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.

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

    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...

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

    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...

  12. 78 FR 42966 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  13. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  14. 77 FR 41790 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  15. 78 FR 58315 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  16. 75 FR 10488 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  17. 75 FR 11551 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

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

    PaulSimonMuhle-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.

  19. 明党参活性成分及药理作用研究进展%Overview of studies on active constituents and pharmacological actions of Changium smy rnioides

    季晓; 宣槐斌; 黄宝康

    2015-01-01

    Changium smyrnioides (C . smyrnioides) Wolff is one species of monotypic genus in the A piaceae family w hich is a Chinese endemic species medicinal plant .It has the effect of nourishing the body ,improving health ,moiste‐ning the lung ,eliminating sputum and suppressing cough ,regulating stomach and relieving vomiting ,neutralizing toxins and subsiding swelling .C .smyrnioides as one kind of medicinal food and tonic agents ,is one of the important export medicinal ma‐terials .The tonic effect may be related with immuno‐regulatory ,anti‐fatigue and anti‐stress activities ,and polysaccharides are the main active constituents .The progress of the active constituents and pharmacological actions of C .smyrnioides are re‐viewed to provide basis for future rational development and utilization .%明党参是中国特有单种属植物,有滋补强壮、润肺化痰、养阴和胃及平肝解毒之功效,常作药膳及滋补强壮剂用,是我国外贸出口药材的重要品种之一。明党参的滋补强壮作用与其增强机体免疫功能、缓解疲劳和提高机体适应能力有关,多糖是其主要的活性成分。对近年来明党参活性成分及药理作用方面的研究进行综述,为合理开发和综合利用明党参提供依据。

  20. Study of gamma radiation from 60Co effects on Apis mellifera venom: biochemical, pharmacological and immunological aspects

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. Ionizing radiation is able to modify molecular structures affecting the biological properties of proteins. It decreases toxic and enzymatic activities and so, it appears promising as a venom detoxification tool. The main objective of this work was to study the effects of gamma radiation on bee venom, regarding biochemical, pharmacological and immunological aspects. Africanized Apis mellifera whole venom (2 mg/ml) in 0.15 M NaCl solution was irradiated with 2 kGy in a 60Co source. Native and irradiated bee venoms were submitted to high performance size exclusion chromatography (Tosohaas G2000SW column), high performance reversed phase chromatography in a C-18 column under water/acetonitrile gradient, SDS-PAGE. For both venoms studies have been carried out in UV absorption spectrum, protein concentration, hemolytic activity, and PLA2 activity analysis, lethality assay (LD50). Biodistribution studies was carried out after labelling native and irradiated bee venom with 99mTc. The results showed that gamma radiation did not change the protein concentration nor its immunogenicity, although it could be observed that irradiated bee venom UV spectrum and SDS-PAGE profile presented differences when compared to native bee venom. This suggests that some structural alterations in bee venom components could have occurred after irradiation. HPLC-RP profiles showed that gamma radiation could have caused conformational changes, such as unfolding of molecule chains, changing their hydrophobic groups exposuring. The hemolytic and the PLA2 activities of irradiated bee venom were smaller than the native ones. The gamma radiation diminished the toxicity of bee venom, but did not abolish its bioactivity, like hemolysis. Biodistribution studies showed

  1. Effective average action for gauge theories and exact evolution equations

    We propose a new nonperturbative evolution equation for Yang-Mills theories. It describes the scale dependence of an effective action. The running of the nonabelian gauge coupling in arbitrary dimension is computed. (orig.)

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

    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.

  3. Effects of some pharmacological agents on the survival of unipedicled venous flaps: an experimental study.

    Askar, I; Saray, A; Gurlek, A; Sevin, K; Sabuncuoglu, B T

    2001-01-01

    Clinical and experimental studies have been conducted to improve the survival of venous flaps. As a result of these studies, although various survival mechanisms were raised, none obtained satisfactory information. Venous stasis, and the resultant venous thrombosis, is a factor that decreases the survival of venous flaps. In this study, we evaluated the effects of two antiinflammatory agents, etodolac and etofenamate, on the survival of unipedicled venous flaps. In this study, 35 male New Zealand white rabbits (3,500-4,000 g) (70 ears) were used. Perichondrocutaneous flaps, 3 x 4.5 cm in size, were designed and raised, keeping the central veins intact in the middle of venous flap. Central arteries and nerves were ligated and transected both proximally and distally, to prepare unipedicled venous flaps. A silicone sheet was placed between the cartilage tissue and flap, to prevent blood flow and revascularization beneath. The subjects were divided into seven groups, consisting of five rabbits (10 ears). In the negative control group (group I), the single vascular pedicle of venous flaps, central veins were ligated and flaps sutured into their own place as the composite graft. In the positive control group (group II), after venous flaps were prepared, normal saline, 0.2 mL, was given subcutaneously. In the first of five experimental groups (group III), unfractionated heparin (100 U/day) was given subcutaneously. In the second experimental group (group IV), etodolac (5 mg/kg/day) was given subcutaneously. In the third experimental group (group V), etophenamate (5 mg/kg/day) was given orally through a feeding tube. In the fourth experimental group (group VI), parnaparin (5 anti-Xa U/kg/day) was given subcutaneously. In the fifth experimental group (group VII), nadroparin (5 anti-Xa U/kg/day) was given subcutaneously, about 7 days postoperatively. At the eighth postoperative day, surviving areas of venous flaps were measured, and the results were evaluated by Kruskal

  4. Morphology, pharmacological activity, pharmaceutical preparation, doses and side effect of Coccinia indica (Wight & Arn.): An overview

    Mayank Kumar; Shashi Alok; Sanjay Kumar Jain; Amita Verma; Alok Mahor; Monika Sabharwal

    2013-01-01

    Traditional system of medicine consists of large number of plants with various medicinal and pharmacological importances and hence represents a priceless tank of new bioactive molecules. Coccinia indica belongs to the family Cucurbitaceae. It is a rapidly growing, perennial climber or trailing vine. Traditionally different parts of this plant namely the roots, leaves and fruits are used in folklore medicine for several purposes like jaundice, diabetes, wound healing, ulcers, stoma...

  5. Impact of Benign Prostatic Hyperplasia Pharmacological Treatment on Transrectal Prostate Biopsy Adverse Effects

    Marina Zamuner; Ciro Eduardo Falcone; Arnaldo Amstalden Neto; Tomás Bernardo Costa Moretti; Luis Alberto Magna; Fernandes Denardi; Leonardo Oliveira Reis

    2014-01-01

    Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients w...

  6. Arsenic: health effects, mechanisms of actions, and research issues.

    Abernathy, C O; Liu, Y. P.; Longfellow, D; Aposhian, H V; Beck, B.; Fowler, B.; Goyer, R; Menzer, R.; Rossman, T; Thompson, C.; Waalkes, M

    1999-01-01

    A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Alth...

  7. Holographic RG flow and the quantum effective action

    The calculation of the full (renormalized) holographic action is undertaken in general Einstein-scalar theories. The appropriate formalism is developed and the renormalized effective action is calculated up to two derivatives in the metric and scalar operators. The holographic RG equations involve a generalized Ricci flow for the space-time metric as well as the standard β-function flow for scalar operators. Several examples are analyzed and the effective action is calculated. A set of conserved quantities of the holographic flow is found, whose interpretation is not yet understood. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. New Development on Pharmacological Effects ofPunica Granatum L.%石榴药理研究新进展

    刘宇; 蔡霞; 曾勇; 王平; 孟宪丽; 张艺

    2015-01-01

    本文主要对近年来国内外石榴的药理研究进展进行综述.石榴药用历史悠久,不同部位在中医药与民族医药中应用广泛,其化学成分以鞣质类、黄酮类、生物碱和有机酸化合物为主,具有明显的药理活性.近年来,有关石榴的抗菌抗病毒、降血糖、抗肿瘤、调血脂及抗氧化、免疫调节等药理研究进展迅速.通过整理归纳并科学的分析石榴的功效及其新的药理学研究成果,以期能对石榴的研究、临床应用及相关产品的开发利用提供依据.%This article reviewed pharmacological study development of Punica granatum L. both at home and abroad in recent years. P. granatum has a long medical usage history. Different parts of P. granatum have wide applications in both traditional Chinese medicine (TCM) and other ethnic medicine. Its main chemical compositions were tannins, flavonoids, alkaloids and organic acids. It has obvious pharmacological activities. In recent years, the pharmacological research progress on P. granatum in terms of antibacterial, antiviral, hypoglycemic, antitumor, adjusting blood lipids, antioxidant, and immunoregulation has rapid development. The scientific collection and analysis on effects and new pharmacological research results of P. granatum are hoped to provide references for the study, clinical application, development and utilization of P. granatum and its products.

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

    Bhattacharya, Jyotirmoy; Bhattacharyya, Sayantani; Rangamani, Mukund

    2013-01-01

    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 ...

  10. Pharmacologically effective red yeast rice preparations marketed as dietary supplements illustrated by a case report.

    Venhuis, B J; van Hunsel, F; van de Koppel, S; Keizers, P H J; Jeurissen, S M F; De Kaste, D

    2016-03-01

    This paper reports a typical statin-related adverse reaction from a red yeast rice (RYR) supplement and the analytical findings from the supplement. It also examines the regulatory framework governing botanical supplements in Europe. Two key events that shaped the current regulatory framework are reviewed. First, the Hecht-Pharma judgement by the European Court of Justice (ECJ) that inverted the precautionary principle in the Medicines Act to a reactionary principle. Following the Hecht-Pharma judgement, pharmacological active dietary supplements can be sold until sufficient signals of harm show that they are an unregistered medicine, placing a huge burden on regulatory authorities. Secondly, the European Food Safety Authority (EFSA) in 2011 approved the first health claim for pharmacologically active RYR dietary supplements. If the current regulatory status for pharmacologically active RYR dietary supplements does not permit adequate warning and active monitoring of adverse drug reactions, then the current regulatory framework may not be adequate to ensure consumer safety.Copyright © 2016 John Wiley & Sons, Ltd. PMID:26810781

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

    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.

  12. Quantum effective action from the AdS/CFT correspondence

    Skenderis, K; Skenderis, Kostas; Solodukhin, Sergey N.

    2000-01-01

    We obtain an Einstein metric of constant negative curvature given an arbitrary boundary metric in three dimensions, and a conformally flat one given an arbitrary conformally flat boundary metric in other dimensions. In order to compute the on-shell value of the gravitational action for these solutions, we propose to integrate the radial coordinate from the boundary till a critical value where the bulk volume element vanishes. The result, which is a functional of the boundary metric, provides a sector of the quantum effective action common to all conformal field theories that have a gravitational description. We verify that the so-defined boundary effective action is conformally invariant in odd (boundary) dimensions and has the correct conformal anomaly in even (boundary) dimensions. In three dimensions and for arbitrary static boundary metric the bulk metric takes a rather simple form. We explicitly carry out the computation of the corresponding effective action and find that it equals the non-local Polyakov...

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

    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.

  14. Urban Heat Island Effect Actions - Neighborhood Data

    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...

  15. Effect of mutagen combined action on Chlamydomonas reinhardtii cells. II

    The effect of UV radiation and UV radiation combined with alkylnitrosourea derivatives (N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea) was observed on survival of cells of the algae Chlamydomonas reinhardtii. In particular, single parts were evaluated of the overall lethal effect - dying of cells before division and dying of cells after division. It was found that the combined action of low doses of UV radiation and alkylnitrosoureas result in a pronounced protective effect which manifests itself by a higher frequency of surviving cells than was that effected by the action of alkylnitrosoureas alone. As a result of combined action with higher doses of UV radiation this effect is lost, and the resultant values will come close to the theoretically anticipated values. This gradual transition from a protective to an additive effect mainly manifests itself by changes in the proportion of cells dying before division. (author)

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

    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.

  17. 牛蒡的药理作用研究进展%Advances in Pharmacological Effects of Arctium Lappa L.

    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.

  18. Radiosensitizers action on Iodine 131 therapeutical effect

    Present studies were aimed to research the possible application of a radiosensitizer, nicotinamide, to increase the therapeutical effect of radioiodine. There were used goitrous and normal rats with growing dose of Iodine 131, with and without simultaneous treatment with nicotinamide. The obtained results show that the nicotinamide treatment importantly increases the thyroid radio destructive effect induced by radioiodine. Under these experimental conditions, nicotinamide induces to a significant increase of thyroid vascularisation, without changes in the proteins ADP-ribosylation activity. These results show, for the first time, the radiosensitizer effect of nicotinamide in front of Iodine 131 and give the possibility of using it in the treatment of hyperthyroid or thyroid difference cancer patients. (author)

  19. Fractional Effective Action at strong electromagnetic fields

    Kleinert, Hagen; Xue, She-Sheng

    2013-01-01

    In 1936, Weisskopf showed that for vanishing electric or magnetic fields the strong-field behavior of the one loop Euler-Heisenberg effective Lagrangian of quantum electro dynamics (QED) is logarithmic. Here we generalize this result for different limits of the Lorentz invariants \\(\\vec{E}^2-\\vec{B}^2\\) and \\(\\vec{B}\\cdot\\vec{E}\\). The logarithmic dependence can be interpreted as a lowest-order manifestation of an anomalous power behavior of the effective Lagrangian of QED, with critical exponents \\(\\delta=e^2/(12\\pi)\\) for spinor QED, and \\(\\delta_S=\\delta/4\\) for scalar QED.

  20. Background independent effective action from D=1 matrix model

    We derive the background independent form of the Das-Jevicki action. The tachyon terms are given to all orders by a generally covariant form of the Das-Jevicki action. The graviton-dilaton sector is the usual low energy effective action. This enables us to examine questions such as the back reaction of the tachyon on the metric. In particular the reason why the usual Liouville term is an exact solution of the conformal invariance conditions, as well as the fact that it has no back reaction, become manifest. We comment on the propagation of a tachyonic perturbation in the background of a black-hole metric. (orig.)

  1. Effectiveness of modified seminars as a teaching-learning method in pharmacology

    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.

  2. Pharmacological activities of Curcuma caesia

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

    2011-07-01

    ... 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... April 13, 2010, Advisory Committee for Pharmaceutical Science and Clinical Pharmacology...

  4. 76 FR 3912 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    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...

  5. Morphology, pharmacological activity, pharmaceutical preparation, doses and side effect of Coccinia indica (Wight & Arn.: An overview

    Mayank Kumar

    2013-11-01

    Full Text Available Traditional system of medicine consists of large number of plants with various medicinal and pharmacological importances and hence represents a priceless tank of new bioactive molecules. Coccinia indica belongs to the family Cucurbitaceae. It is a rapidly growing, perennial climber or trailing vine. Traditionally different parts of this plant namely the roots, leaves and fruits are used in folklore medicine for several purposes like jaundice, diabetes, wound healing, ulcers, stomach ache, skin disease, fever, asthma, cough. The leaf and its constituents have been reported to possess hypoglycaemic, hypolipidemic and antioxidant properties. This review provides adequate information to develop suitable therapeutics out of these plant parts.

  6. Renormalization and Effective Actions for General Relativity

    Neugebohrn, Falk

    2007-01-01

    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 Eucl...

  7. Renormalization and effective actions for general relativity

    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.)

  8. Renormalization and effective actions for general relativity

    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.)

  9. An investigation of sex-linked differences to the toxic and to the pharmacological actions of difenacoum: studies in mice and rats.

    Winn, M J; Clegg, J A; Park, B K

    1987-03-01

    We have investigated the actions of the coumarin anticoagulant, difenacoum, in male and female rats and mice. In our first experiment difenacoum (0.5 mg kg-1) killed 50% of male mice within 9 days of its administration, whereas no female mice died during this study. In a second group of experiments, the anticoagulant effect of difenacoum in male and female rats was determined. Under resting conditions, the prothrombin complex activities (PCA) of male and female rats were not significantly different. Over the first 24 h after administration of difenacoum (0.4 mg kg-1 i.p.), there was a monoexponential fall in PCA in both sexes. However, 6, 12 and 24 h after difenacoum, the PCA in male rats was significantly (P less than 0.05) lower than in female rats. PCA began to recover over the subsequent 48 h in both sexes, during which time there was marked variability in recovery in female rats. The difference between the onset of action of difenacoum in male and female rats did not appear to be due to a greater rate of elimination of the drug in female rats, since the plasma concentrations of difenacoum 24 h after its administration were the same in both sexes. The concentration of vitamin K1 in rat liver was also investigated. Vitamin K1 levels were 35.1 +/- 18.6 ng (g liver)-1 (male), and 29.4 +/- 5.4 ng (g liver)-1 (females) in control rats, but 24 h after difenacoum, vitamin K1 levels were either very low, or undetectable in all rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2883288

  10. Pharmacological approach to acute pancreatitis

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

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may....... Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted....

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

    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.

  12. Boldine action against the stannous chloride effect.

    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. PMID:10624900

  13. On the new definition of off-shell effective action

    We analyze the recently proposed definition of the off-shell, gauge invariant, gauge-independent, effective action GAMMA, utilizing an invariant metric on the field space. It is shown how to establish correspondence between GAMMA and the standard effective action, calculated in some particular (Landau-type) gauge. Several examples are explicitly discussed, including Yang-Mills theory, the effective potential in scalar QED, and one-loop quantum gravity. Generalization to the case of super-invariant theories (e.g. super-Yang Mills and supergravity) is also presented. (orig.)

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

    Garbrecht, Björn; Millington, Peter

    2016-05-01

    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 Teresi, we give an example of how the external sources can be used to preserve global symmetries in truncations of the 2PI effective action. Specifically, in the context of an O (2) model with spontaneous symmetry breaking, we show that this approach allows the Hartree-Fock approximation to be re-organized, such that the Goldstone boson remains massless algebraically in the symmetry-broken phase and we obtain the correct second-order thermal phase transition.

  15. Stratospheric ozone loss, ultraviolet effects and action spectroscopy

    Coohill, Thomas P.

    The major effect of stratospheric ozone loss will be an increase in the amount of ultraviolet radiation reaching the ground. This increase will be entirely contained within the UV-B (290-320nm). How this will impact life on Earth will be determined by the UV-B photobiology of exposed organisms, including humans. One of the analytical methods useful in estimating these effects is Action Spectroscopy (biological effect as a function of wavelength). Carefully constructed action spectra will allow us to partially predict the increase in bio-effect due to additional UV exposure. What effect this has on the organism and the system in which the organism resides is of paramount importance. Suitable action spectra already exist for human skin cancer, human cell mutation and killing, and for one immune response. Comprehensive and widely applicable action spectra for terrestrial and aquatic plant responses are being generated but are not yet suitable for extensive analysis. There is little data available for animals, other than those experiments completed in the laboratory as model systems for human studies. Some polychromatic action spectra have proven useful in determining the possible impact of ozone loss on biological systems. The pitfalls and limits of this approach will be addressed.

  16. Effective action of softly broken supersymmetric theories

    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. (author)

  17. Early markers of ongoing action-effect learning

    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.

  18. The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex.

    Spencer, Robert C; Devilbiss, David M; Berridge, Craig W

    2015-06-01

    Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. In contrast, while the striatum is a critical participant in PFC-dependent cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g., working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention-deficit/hyperactivity disorder and other conditions associated with PFC dysregulation. PMID:25499957

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

    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).

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

    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).

  1. Action and perception in social contexts: Intentional binding for social action effects

    Roland Pfister

    2014-09-01

    Full Text Available The subjective experience of controlling events in the environment alters the perception of these events. For instance, the interval between one’s own actions and their consequences is subjectively compressed – a phenomenon known as intentional binding. In two experiments, we studied intentional binding in a social setting in which actions of one agent prompted a second agent to perform another action. Participants worked in pairs and were assigned to a “leader” and a “follower” role, respectively. The leader’s key presses triggered (after a variable interval a tone effect and this tone served as go signal for the follower to perform a keypress as well. Leaders and followers estimated the interval between the leader’s keypress and the following tone, or the interval between the tone and the follower’s keypress. The leader showed reliable intentional binding for both intervals relative to the follower’s estimates. These results indicate that human agents experience a pre-reflective sense of agency for genuinely social consequences of their actions.

  2. Laxative effects and mechanism of action of Brazilian green propolis

    Kakino Mamoru; Izuta Hiroshi; Tsuruma Kazuhiro; Araki Yoko; Shimazawa Masamitsu; Ichihara Kenji; Hara Hideaki

    2012-01-01

    Abstract Background Brazilian green propolis is reported to have wide range of biological properties including antibacterial, anti-inflammatory, anti-influenza, and antioxidant activities. In the digestive system, a protective effect of propolis on gastric ulcer has been reported, but a laxative effect has not yet been reported. We investigated the effect and the mechanism of action of water and ethanol extracts of Brazilian green propolis. Methods We examined the laxative effect of propolis ...

  3. Effects of pH and Iminosugar Pharmacological Chaperones on Lysosomal Glycosidase Structure and Stability

    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

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

    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...

  5. In vivo EPR: an effective new tool for studying pathophysiology, physiology and pharmacology

    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)

  6. Effective actions near singularities: the STU-model

    We derive the low energy effective action of the STU-model in four and five dimensions near the line T=U where SU(2) gauge symmetry enhancement occurs. By 'integrating in' the light W± bosons together with their superpartners, the quantum corrected effective action becomes non-singular at T=U and manifestly SU(2) invariant. The four-dimensional theory is found to be consistent with modular invariance and the five-dimensional decompactification limit. (Abstract Copyright [2003], Wiley Periodicals, Inc.)

  7. Brane Effective Actions, Kappa-Symmetry and Applications

    Simon, Joan

    2011-01-01

    This is a review on brane effective actions, their symmetries and some of its applications. Its first part uncovers 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 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 non-tr...

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

    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...

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

    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.)

  10. Effective action for the field equations of charged black holes

    We consistently reduce the equations of motion for the bosonic N = 2 supergravity action, using a multi-centered black hole ansatz for the metric. This reduction is done in a general, non-supersymmetric setup, in which we extend concepts of BPS black hole technology. First we obtain a more general form of the black hole potential, as part of an effective action for both the scalars and the vectors in the supergravity theory. Furthermore, we show that there are extra constraints specifying the solution, which we calculate explicitly. In the literature, these constraints have already been studied in the one-center case. We also show that the effective action we obtain for non-static metrics can be linked to the 'entropy function' for the spherically symmetric case, as defined by Sen (2005 J. High Energy Phys. JHEP09(2005)038) and Cardoso et al (2007 J. High Energy Phys. JHEP03(2007)085)

  11. Resummed effective action in the world-line formalism

    Auer, T; Zahlten, C; Auer, Thomas; Schmidt, Michael G.; Zahlten, Claus

    2004-01-01

    Using the world-line method we resum the scalar one-loop effective action. This is based on an exact expression for the one-loop action obtained for a background potential and a Taylor expansion of the potential up to quadratic order in x-space. We thus reproduce results of Masso and Rota very economically. An alternative resummation scheme is suggested using ``center of mass'' based loops which is equivalent under the assumption of vanishing third and higher derivatives in the Taylor expansion but leads to simplified expressions. In an appendix some general issues concerning the relation between world-line integrals with fixed end points versus integrals with fixed center are clarified. We finally note that this method is also very valuable for gauge field effective actions where it is based on the Euler--Heisenberg type resummation.

  12. Resumed effective action in the world-line formalism

    Using the world-line method we resume the scalar one-loop effective action. This is based on an exact expression for the one-loop action obtained for a background potential and a Taylor expansion of the potential up to quadratic order in x-space. We thus reproduce results of Masso and Rota very economically. An alternative resummation scheme is suggested using 'center of mass' based loops which is equivalent under the assumption of vanishing third and higher derivatives in the Taylor expansion but leads to simplified expressions. In an Appendix A some general issues concerning the relation between world-line integrals with fixed end points versus integrals with fixed center are clarified. We finally note that this method is also very valuable for gauge field effective actions where it is based on the Euler-Heisenberg type resummation

  13. Phyto-pharmacology of Celastrus paniculatus: An Overview

    Bhanumathy, M.; S B Chandrasekar; Uma Chandur; Somasundaram, T

    2010-01-01

    Celastrus paniculatus (CP), a traditional Ayurvedic medicinal plant used for centuries as a memory enhancing, anti-inflammatory, analgesic, sedative and antiepileptic agent. The seed extract has been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, anticonvulsant and other pharmacological effects of CP preparations/extra...

  14. Pharmacological screening of the essential oil of pavonia oderata willd.

    Nakhare, Seema; Garg, S. C.; Bhagwat, A.W.

    1997-01-01

    Essential oil obtained from the rhizomes of pavonia odorata willd has been found to posses a number of interesting pharmacological actions on various parameters. The essential oil produced fall in blood pressure of anaesthethized dog and caused cardiac inhibition in frog's isolated heart. The essential oil caused relaxation of the rabbit's intestine and had no effect on rectus abdominus muscle of frog, but reduced the spasmogenic effect of acetylcholine and potassium.

  15. Social Pharmacology: Expanding horizons

    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.

  16. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect.

    Jaebok Choi

    Full Text Available We have recently reported that interferon gamma receptor deficient (IFNγR-/- allogeneic donor T cells result in significantly less graft-versus-host disease (GvHD than wild-type (WT T cells, while maintaining an anti-leukemia or graft-versus-leukemia (GvL effect after allogeneic hematopoietic stem cell transplantation (allo-HSCT. We demonstrated that IFNγR signaling regulates alloreactive T cell trafficking to GvHD target organs through expression of the chemokine receptor CXCR3 in alloreactive T cells. Since IFNγR signaling is mediated via JAK1/JAK2, we tested the effect of JAK1/JAK2 inhibition on GvHD. While we demonstrated that pharmacologic blockade of JAK1/JAK2 in WT T cells using the JAK1/JAK2 inhibitor, INCB018424 (Ruxolitinib, resulted in a similar effect to IFNγR-/- T cells both in vitro (reduction of CXCR3 expression in T cells and in vivo (mitigation of GvHD after allo-HSCT, it remains to be determined if in vivo administration of INCB018424 will result in preservation of GvL while reducing GvHD. Here, we report that INCB018424 reduces GvHD and preserves the beneficial GvL effect in two different murine MHC-mismatched allo-HSCT models and using two different murine leukemia models (lymphoid leukemia and myeloid leukemia. In addition, prolonged administration of INCB018424 further improves survival after allo-HSCT and is superior to other JAK1/JAK2 inhibitors, such as TG101348 or AZD1480. These data suggest that pharmacologic inhibition of JAK1/JAK2 might be a promising therapeutic approach to achieve the beneficial anti-leukemia effect and overcome HLA-barriers in allo-HSCT. It might also be exploited in other diseases besides GvHD, such as organ transplant rejection, chronic inflammatory diseases and autoimmune diseases.

  17. Ocular pharmacology.

    Novack, Gary D; Robin, Alan L

    2016-05-01

    Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many anterior segment diseases are treated pharmacologically through eye drops, which have an implied therapeutic index of local therapy. Unlike oral dosage forms administered for systemic diseases, eyedrops require patients not only to adhere to treatment, but to be able to accurately perform-ie, instill drops correctly. Anatomical and physiological barriers make topical delivery to the anterior chamber challenging-in some cases more challenging than absorption through the skin, nasal passages, or gut. Treatment of the posterior segment (eg, vitreous, retina, choroid, and optic nerve) is more challenging due to additional barriers. Recently, intravitreal injections have become a standard of care with biologics for the treatment of macular degeneration and other diseases. Although the eye has esterases, hydroxylases, and transporters, it has relatively little CYP450 enzymes. Because it is challenging to obtain drug concentrations at the target site, ocular clinical pharmacokinetics, and thus pharmacokinetic-pharmacodynamic interactions, are rarely available. Ophthalmic pharmaceuticals require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Although applied locally, ocular medications may be absorbed systemically, which results in morbidity and mortality (eg, systemic hypotension, bronchospasm, and bradycardia). PMID:26360129

  18. Zeta function regularization and effective action in curved spacetime. 16

    This article expounds on a sophisticated regularization technique for quantum field theories in arbitrary gravitational fields: the zeta function regularization. The effective action in curved spacetime is obtained and used to discuss phase transitions in the De Sitter Universe. (author). 5 refs.; 6 figs.; 1 tab

  19. Boundary Conditions for NHEK through Effective Action Approach

    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. (the physics of elementary particles and fields)

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

    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...

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

    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…

  2. Effective action approach to dynamical generation of fermion mixing

    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.

  3. Finiteness of the Coulomb gauge QCD perturbative effective action

    Andraši, A., E-mail: aandrasi@irb.hr [Vlaška 58, Zagreb (Croatia); Taylor, J.C., E-mail: jct@damtp.cam.ac.uk [DAMTP, University of Cambridge, Cambridge (United Kingdom)

    2015-05-15

    At 2-loop order in the Coulomb gauge, individual Feynman graphs contributing to the effective action have energy divergences. It is proved that these cancel in suitable combinations of graphs. This has previously been shown only for transverse external fields. The calculation results in a generalization of the Christ–Lee term which was inserted into the Hamiltonian.

  4. Finiteness of the Coulomb gauge QCD perturbative effective action

    Andrasi, A

    2015-01-01

    At 2-loop order in the Coulomb gauge, individual Feynman graphs contributing to the effective action have energy divergences. It is proved that these cancel in suitable combinations of graphs. This has previously been shown only for transverse external fields. The calculation results in a generalization of the Christ-Lee term which was inserted into the Hamiltonian.

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

    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.)

  6. 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

    陈薇; 付翔; 黄鹂莺姿; 毛柳珺; 戴莉琳

    2015-01-01

    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。%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.

  7. 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

    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。

  8. Effective action for the Abelian Higgs model in FLRW

    George, Damien P.; Mooij, Sander(Nikhef, Science Park 105, Amsterdam, 1098 XG The Netherlands); Postma, Marieke

    2012-01-01

    We compute the divergent contributions to the one-loop action of the U(1) Abelian Higgs model. The calculation allows for a Friedmann-Lemaitre-Robertson-Walker space-time and a time-dependent expectation value for the scalar field. Treating the time-dependent masses as two-point interactions, we use the in-in formalism to compute the first, second and third order graphs that contribute quadratic and logarithmic divergences to the effective scalar action. Working in R-xi gauge we show that the...

  9. Effective action for the Abelian Higgs model in FLRW

    George, Damien P; Postma, Marieke

    2012-01-01

    We compute the divergent contributions to the one-loop action of the U(1) Abelian Higgs model. The calculation allows for a Friedmann-Lemaitre-Robertson-Walker space-time and a time-dependent expectation value for the scalar field. Treating the time-dependent masses as two-point interactions, we use the in-in formalism to compute the first, second and third order graphs that contribute quadratic and logarithmic divergences to the effective scalar action. Working in R-xi gauge we show that the result is gauge invariant upon using the equations of motion.

  10. Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

    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

  11. Pharmacological Evaluation of Total Alkaloids from Nux Vomica: Effect of Reducing Strychnine Contents

    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.

  12. Pharmacological antagonism of the actions of group II and III mGluR agonists in the lateral perforant path of rat hippocampal slices.

    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

  13. Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin®) and metallic silver.

    Whitehouse, Michael; Butters, Desley; Vernon-Roberts, Barrie

    2013-08-01

    This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag°) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag° were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin(®)) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag° or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995

  14. Effect of mutagen combined action on Chlamydomonas Reinhardtii cells. I

    The effect was investigated of single and combined actions of alkylnitrosourea derivatives (N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea) and UV-radiation on the survival of cells of Chlamydomonas reinhardtii algae in dependence on the sequence of application of mutagens and on the given conditions of cultivation following mutagen activity. In particular, the single phases were investigated of the total lethal effect, i.e., the death of cells before division and their death after division. The most pronounced changes in dependence on the sequence of application of mutagens and on the given conditions of cultivation were noted in cell death before division. In dependence on the sequence of application of mutagens, the effect of the combined action on the survival of cells changed from an additive (alkylnitrosourea + UV-radiation) to a protective effect (UV-radiation + alkylnitrosourea). (author)

  15. Computing the Effective Action with the Functional Renormalization Group

    Codello, Alessandro; Rachwal, Leslaw; Tonero, Alberto

    2015-01-01

    The "exact" or "functional" renormalization group equation describes the renormalization group flow of the effective average action $\\Gamma_k$. The ordinary effective action $\\Gamma_0$ can be obtained by integrating the flow equation from an ultraviolet scale $k=\\Lambda$ down to $k=0$. We give several examples of such calculations at one-loop, both in renormalizable and in effective field theories. We use the results of Barvinsky, Vilkovisky and Avramidi on the non-local heat kernel coefficients to 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.

  16. Computing the effective action with the functional renormalization group

    Codello, Alessandro; Percacci, Roberto; Rachwał, Lesław; Tonero, Alberto

    2016-04-01

    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 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.

  17. Action video game training reduces the Simon Effect.

    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. PMID:26238760

  18. The end-state comfort effect facilitates joint action.

    Herbort, Oliver; Koning, Arno; van Uem, Janet; G J Meulenbroek, Ruud

    2012-03-01

    Motor experts can accurately predict the future actions of others by observing their movements. This report describes three experiments that investigate such predictions in everyday object manipulations and test whether these predictions facilitate responses to the actions of others. Observing video excerpts showing an actor reaching for a vertically mounted dial, participants in Experiment 1 needed to predict how the actor would rotate it. Their predictions were specific to the direction and extent of the dial rotation and improved proportionate to the length of the video clip shown. Testing whether such predictions facilitate responses, in the subsequent experiments responders had to undo an actor's actions, back-rotating a dial (Exp 2) and a bar (Exp 3). The responders' actions were initiated faster when the actors' movements obeyed the so-called end-state comfort principle than when they did not. Our experiments show that humans exploit the end-state comfort effect to tweak their predictions of the future actions of others. The results moreover suggest that the precision of these predictions is mediated by perceptual learning rather than by motor simulation. PMID:22321453

  19. Invariant effective actions, cohomology of homogeneous spaces and anomalies

    D`Hoker, E. [California Univ., Los Angeles, CA (United States). Dept. of Physics

    1995-10-02

    We construct the most general local effective actions for Goldstone boson fields associated with spontaneous symmetry breakdown from a group G to a subgroup H. In a preceding paper, it was shown that any G-invariant term in the action, which results from a non-invariant Lagrangian density, corresponds to a non-trivial generator of the de Rham cohomology classes of G/H. Here, we present an explicit construction of all the generators of this cohomology for any coset space G/H and compact, connected group G. Generators contributing to actions in 4-dimensional space-time arise either as products of generators of lower degree such as the Goldstone-Wilczek current, or are of the Wess-Zumino-Witten type. The latter arise if and only if G has a non-zero G-invariant symmetric d-symbol, which vanishes when restricted to the subgroup H, i.e. when G has anomalous representations in which H is embedded in an anomaly free way. Coupling of additional gauge fields leads to actions whose gauge variation coincides with the chiral anomaly, which is carried here by Goldstone boson fields at tree level. Generators contributing to actions in 3-dimensional space-time arise as Chern-Simons terms evaluated on connections that are composites of the Goldstone field. (orig.).

  20. Invariant effective actions, cohomology of homogeneous spaces and anomalies

    We construct the most general local effective actions for Goldstone boson fields associated with spontaneous symmetry breakdown from a group G to a subgroup H. In a preceding paper, it was shown that any G-invariant term in the action, which results from a non-invariant Lagrangian density, corresponds to a non-trivial generator of the de Rham cohomology classes of G/H. Here, we present an explicit construction of all the generators of this cohomology for any coset space G/H and compact, connected group G. Generators contributing to actions in 4-dimensional space-time arise either as products of generators of lower degree such as the Goldstone-Wilczek current, or are of the Wess-Zumino-Witten type. The latter arise if and only if G has a non-zero G-invariant symmetric d-symbol, which vanishes when restricted to the subgroup H, i.e. when G has anomalous representations in which H is embedded in an anomaly free way. Coupling of additional gauge fields leads to actions whose gauge variation coincides with the chiral anomaly, which is carried here by Goldstone boson fields at tree level. Generators contributing to actions in 3-dimensional space-time arise as Chern-Simons terms evaluated on connections that are composites of the Goldstone field. (orig.)

  1. 黄芪的药理作用在运动领域的研究综述%A study summary of the astragalus membranaceus’s pharmacologic actions in sports field

    贾瑞红

    2016-01-01

    从生物化学角度出发,阐述了黄芪提取液具有提高机体抗运动性疲劳、机体耐力和增强机体免疫力的作用,发掘黄芪的药理作用在运动领域的研究,从而更好地为运动训练服务,使运动员的竞技能力水平得到提高。%It is said from biochemistry that the extracting solution of astragalus membranaceus has the function of antifatigue, developing endurance, strengthening boost immunity, to explore the astragalus membranaceus ’s pharmacologic actions in sports field can benefit serving for sports training, and at last develop the athletes ’ competitive capacity level.

  2. Rehmannia glutinosa: review of botany, chemistry and pharmacology.

    Zhang, Ru-Xue; Li, Mao-Xing; Jia, Zheng-Ping

    2008-05-01

    Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish Yin and invigorate the kidney in traditional Chinese medicine (TCM) and has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development. PMID:18407446

  3. Pharmacologic treatment of sex offenders with paraphilic disorder.

    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. PMID:23572328

  4. 黄连素药理作用研究进展%The progress of berberine's pharmacological effects

    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。

  5. Evaluation of medical and health economic effectiveness of non-pharmacological secondary prevention of coronary heart disease

    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

  6. Surgical removal of visceral adipose tissue: effects on insulin action.

    Gabriely, Ilan; Barzilai, Nir

    2003-06-01

    Many studies have demonstrated that excess of visceral fat has deleterious effects on insulin action. Mainly, it has been shown to be associated with a decrease in hepatic and peripheral insulin sensitivity, which results in a clinical condition also known as insulin resistance. This report describes a novel experimental method that we employed in order to analyze the particular effects of visceral fat on insulin activity. By extracting visceral fat we were able to distinguish the specific role that it plays in insulin action, and to analyze its effects on the gene expression of a variety of fat-derived peptides, which may be considered to be (at least partially) mediators in the development of the metabolic syndrome and possibly diabetes mellitus. PMID:12762966

  7. Effect of exercise on insulin action in human skeletal muscle

    Richter, Erik; Mikines, K J; Galbo, Henrik;

    1989-01-01

    performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2......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...... 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...

  8. Pharmacology of Iron Transport

    Byrne, Shaina L.; Krishnamurthy, Divya; Wessling-Resnick, Marianne

    2012-01-01

    Elucidating the molecular basis for the regulation of iron uptake, storage, and distribution is necessary to understand iron homeostasis. Pharmacological tools are emerging to identify and distinguish among different iron transport pathways. Stimulatory or inhibitory small molecules with effects on iron uptake can help characterize the mechanistic elements of iron transport and the roles of the transporters involved in these processes. In particular, iron chelators can serve as potential phar...

  9. Effective action for scalar fields in two-dimensional gravity

    We consider a general two-dimensional gravity model minimally or nonminimally coupled to a scalar field. The canonical form of the model is elucidated, and a general solution of the equations of motion in the massless case is reviewed. In the presence of a scalar field all geometric fields (zweibein and Lorentz connection) are excluded from the model by solving exactly their Hamiltonian equations of motion. In this way the effective equations of motion and the corresponding effective action for a scalar field are obtained. It is written in a Minkowskian space-time and does not include any geometric variables. The effective action arises as a boundary term and is nontrivial both for open and closed universes. The reason is that unphysical degrees of freedom cannot be compactly supported because they must satisfy the constraint equation. As an example we consider spherically reduced gravity minimally coupled to a massless scalar field. The effective action is used to reproduce the Fisher and Roberts solutions

  10. FERULIC ACID – COMPREHENSIVE PHARMACOLOGY OF IMPORTANT BIOFLAVONOID

    Shashank B. Kshirsagar et al.

    2012-01-01

    Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is an phenolic compound and an antioxidant found in many staple foods, such as fruits, vegetables, cereals, coffee and in plant constituent exhibiting a wide range of therapeutic effects such as anticancer, antidiabetic, cardio protective and neuroprotective, anti-inflammatory activity. The present review summarizes the most recent literature on FA including its pharmacological actions, preclinical and clinical studies, reported mechanisms of ac...

  11. Misunderstanding that the Effective Action is Convex under Broken Symmetry

    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.

  12. One-loop effective actions and higher spins

    Bonora, L; Prester, P Dominis; Giaccari, S; De Souza, B Lima; Stemberga, T

    2016-01-01

    The idea we advocate in this paper is that the one-loop effective action of a free (massive) field theory coupled to external sources (via conserved currents) contains complete information about the classical dynamics of such sources. We show many explicit examples of this fact for (scalar and fermion) free field theories in various dimensions $d=3,4,5,6$ coupled to (bosonic, completely symmetric) sources with a number of spins. In some cases we also provide compact formulas for any dimension. This paper is devoted to two-point correlators, so the one-loop effective action we construct contains only the quadratic terms and the relevant equations of motion for the sources we obtain are the linearized ones.

  13. Field theory without Feynman diagrams: One-loop effective actions

    In this paper the connection between standard perturbation theory techniques and the new Bern-Kosower calculational rules for gauge theory is clarified. For one-loop effective actions of scalars, Dirac spinors, and vector bosons in a background gauge field, Bern-Kosower type rules are derived without the use of either string theory or Feynman diagrams. The effective action is written as a one-dimensional path integral, which can be calculated to any order in the gauge coupling; evaluation leads to Feynman parameter integrals directly, bypassing the usual algebra required from Feynman diagrams, and leading to compact and organized expressions. This formalism is valid off-shell, is explicitly gauge invariant, and can be extended to a number of other field theories. (orig.)

  14. Laxative effects and mechanism of action of Brazilian green propolis

    Kakino Mamoru

    2012-10-01

    Full Text Available Abstract Background Brazilian green propolis is reported to have wide range of biological properties including antibacterial, anti-inflammatory, anti-influenza, and antioxidant activities. In the digestive system, a protective effect of propolis on gastric ulcer has been reported, but a laxative effect has not yet been reported. We investigated the effect and the mechanism of action of water and ethanol extracts of Brazilian green propolis. Methods We examined the laxative effect of propolis on stool frequency by administering orally an ethanol extract of propolis (EEP or a water extract of propolis (WEP at 10, 50, 100, or 500 mg/kg to normal mice. We then investigated the effects of propolis using constipation model mice induced by two types of drugs, loperamide (a μ opioid receptor agonist and clonidine (an α-2 adrenergic receptor agonist. We also investigated the effects of WEP on gastrointestinal transit and contractional tension of the ileum to uncover the mechanism of action of WEP. Results Treatment with WEP, but not with EEP, significantly increased the weight of stools (p Conclusion These findings indicate that WEP has laxative effects both in normal mice and in clonidine-induced constipation model mice. The laxative effects of WEP might be mediated by increased contractional tension of the ileum exerted at least in part via activation of an acetylcholine receptor.

  15. Overview of safety pharmacology.

    Goineau, Sonia; Lemaire, Martine; Froget, Guillaume

    2013-01-01

    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. PMID:24510755

  16. Light composite Higgs from an effective action for technicolor

    Doff, A.(Universidade Tecnológica Federal do Paraná – UTFPR – DAFIS, Av. Monteiro Lobato Km 04, 84016-210 Ponta Grossa, PR, Brazil); Natale, A. A.; da Silva, P. S. Rodrigues

    2008-01-01

    We compute an effective action for a composite Higgs boson formed by new fermions belonging to a general technicolor non-Abelian gauge theory, using a quite general expression for the fermionic self-energy that depends on a certain parameter (alpha), that defines the technicolor theory from the extreme walking behavior up to the one with a standard operator product expansion behavior. We discuss the values of the trilinear and quadrilinear scalar couplings. Our calculation spans all the possi...

  17. The effective action in Einstein-Maxwell theory

    Considerable work has been done on the one-loop effective action in combined electromagnetic and gravitational fields, particularly as a tool for determining the properties of light propagation in curved space. After a short review of previous work, I will present some recent results obtained using the worldline formalism. In particular, I will discuss various ways of generalizing the QED Euler-Heisenberg Lagrangians to the Einstein-Maxwell case.

  18. The effective action in Einstein-Maxwell theory

    Bastianelli, Fiorenzo; Davila, Jose Manuel; Schubert, Christian

    2008-01-01

    Considerable work has been done on the one-loop effective action in combined electromagnetic and gravitational fields, particularly as a tool for determining the properties of light propagation in curved space. After a short review of previous work, I present some recent results obtained using the worldline formalism. In particular, I will discuss various ways of generalizing the QED Euler-Heisenberg Lagrangian to the Einstein-Maxwell case.

  19. Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings.

    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. PMID:27128862

  20. Brane Effective Actions, Kappa-Symmetry and Applications

    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.

  1. Effects of pharmacological concentrations of dietary zinc oxide on growth of post-weaning pigs: a meta-analysis.

    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 Zinc oxide provided a feasible alternative to in-feed antibiotics to improve growth in post-weaning 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. PMID:23463368

  2. A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain.

    Kuijpers, T; van Middelkoop, M; Rubinstein, S M; Ostelo, R; Verhagen, A; Koes, B W; van Tulder, M W

    2011-01-01

    The objective of this review was to determine the effectiveness of pharmacological interventions [i.e., non-steroid anti-inflammatory drugs (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions were screened for studies fulfilling the inclusion criteria. Then, the literature searches were updated. Only randomized controlled trials on adults (≥18 years) with chronic (≥12 weeks) non-specific LBP and evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work) were included. The GRADE approach was used to determine the quality of evidence. A total of 17 randomized controlled trials was included: NSAIDs (n = 4), antidepressants (n = 5), and opioids (n = 8). No studies were found for muscle relaxants; 14 studies had a low risk of bias. The studies only reported effects on the short term (after stopping their medication. However, both types of medication show more adverse effects than placebo. There seems to be no difference in effect between antidepressants and placebo in patients with non-specific chronic LBP. PMID:20680369

  3. Pharmacology of Quercus infectoria.

    Dar, M S; Ikram, M; Fakouhi, T

    1976-12-01

    The galls of Quercus infectoria (Fagaceae), a commonly available plant in Iran, were studied pharmacologically. Two fractions were employed, a dried acetone-treated methanol extract dissolved in water (Fraction A) and a subfraction prepared by chloroform-methanol extraction (Fraction B). Fraction A was active as an analgesic in rats and significantly reduced blood sugar levels in rabbits. Fraction B had CNS depressant activity. Data obtained with a treadmill indicated a decreased activity ratio by Fraction B, suggesting a possible interference in motor coordination. It potentiated the barbiturate sleeping time significantly without changing the onset time or the loss of the righting reflex. In addition, Fraction B exhibited a moderate antitremorine activity by causing a delay in the onset and a decrease in the severity of tremorine-induced tremors. The local anesthetic action of Fraction B was evident due to the complete blockade of the isolated frog sciatic nerve conduction. PMID:1032663

  4. In silico methods for drug repurposing and pharmacology.

    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. PMID:27080087

  5. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    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

  6. Toward effective ecological risk-management of refinery corrective action

    Cleanup of complex industrial sites, such as refineries, requires risk-based decision tools to ensure that environmentally protective remediation is consistent with current and future land use. However, conventional ecological risk assessment approaches are not well suited for complex industrial sites. Site risk assessments focus on hypothetical chemical risk assuming diverse and undisturbed ecosystems, rather than industrial and disturbed area conditions. In addition, they offer little guidance as to how to make timely and effective risk management decisions. An innovative methodology is proposed to assist industry and regulatory risk managers with rapid EcoRisk reconnaissance and cost-effective remedial decision-making at complex industrial sites. Phase 1 comprises a three-step risk screening of areas of ecological concern at the site, which integrates habitat quality characteristics and potential chemical hazards. It yields an ordering of areas as follows: areas of no significant risk; areas of potentially significant risk; and areas of likely significant risk. A decision rule is then applied to determine appropriate risk management action, including: no action; additional study; and remedial or management action. In Phase 2, additional study is conducted for areas that exhibit potentially significant risk so as to facilitate risk management. This methodology is currently being applied at the 1,300 acre, former Exxon Bayway Refinery in New Jersey

  7. Using the Psychology of Language to Effectively Communicate Actionable Science

    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. 湖北贝母化学成分和药理作用研究进展%Research Advance in Chemical Constituents and Pharmacological Effects of Fritillaria Hupehensis Hsiao

    徐定平; 吴晶晶; 周鑫堂; 郜红利

    2015-01-01

    湖北贝母具有清热润肺、止咳祛痰和平喘的功效,主要含有生物碱类、萜类和其他类化合物,药理作用主要包括镇咳祛痰、平喘、对平滑肌的作用、降压、耐缺氧、扩瞳等作用。该文对湖北贝母的化学成分和药理作用研究进行了综述,以期为其临床应用、药品及健康产品的开发提供依据。%Fritillaria hupehensis has the effects for clearing away heat,moistening lung,relieving cough,expectoration and antiasthma,and mainly contains alkaloids,terpenes and other chemical compounds,its pharmacological actions mainly includes relieving cough and asthma,effect on smooth muscles,reducing blood pressure,bearing hypoxia,pupil dilation,and so on. This paper reviews the chemical constituents and pharmaco-logical effects in order to provide reference for clinical application,and medicines and health products development of Fritillaria hupehensis.

  9. Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

    Inkielewicz-Stepniak I

    2014-04-01

    Full Text Available Iwona Inkielewicz-Stepniak,1,* Maria Jose Santos-Martinez,2–4,* Carlos Medina,2,4 Marek W Radomski2,41Department of Medicinal Chemistry, Medical University Gdansk, Debinki, Poland; 2The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 3School of Medicine, Trinity College Dublin, Dublin, Ireland; 4Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland*These authors contributed equally to this workBackground: 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

  10. 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

    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

  11. Pharmacologic treatment of paraphilias.

    Assumpção, Alessandra Almeida; Garcia, Frederico Duarte; Garcia, Heloise Delavenne; Bradford, John M W; Thibaut, Florence

    2014-06-01

    The treatment of paraphilias remains a challenge in the mental health field. Combined pharmacologic and psychotherapeutic treatment is associated with better efficacy. The gold standard treatment of severe paraphilias in adult males is antiandrogen treatment with cognitive behavioral therapy. Selective serotonin reuptake inhibitors have been used in mild types of paraphilia and in cases of sexual compulsions and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe paraphilic subjects committing sexual offenses. In particular, gonadotropin-releasing hormone analogs have shown high efficacy working in a similar way to physical castration but being reversible at any time. Treatment recommendations, side effects, and contraindications are discussed. PMID:24877704

  12. Effect of Pharmacological Interventions on the Fronto-Cingulo-Parietal Cognitive Control Network in Psychiatric Disorders: A Transdiagnostic Systematic Review of fMRI Studies

    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

  13. Pharmacologic Agents for Chronic Diarrhea.

    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. PMID:26576135

  14. Pharmacological properties of the extract of thymus gland (Thymomodulin-TFX) and its effect on reproduction.

    Kosmala, M; Oledzka, K; Kaszczyńska, M; Lewandowski, K; Przemyk, B; Filczewski, M; Sliwoska, M

    1993-01-01

    The effect of Thymomodulin-TFX on pentetrazole convulsions, tremorine-induced tremor, pain response to intraperitoneal acetic acid injection, hexobarbital sleeping time, isolated guinea pig ileum, isolated rat uterus, rabbit skeletal muscle response, diuresis and corneal response was tested. In addition the effect of TFX on reproduction of albino rats was investigated. In doses up to 20 mg/kg, 8 times higher than clinical doses, TFX did not reveal any unwanted effects. The results of tests widen the security margin for TFX's usage. PMID:8067258

  15. PARENTS' AUTHORITY AND THE EFFECTIVENESS OF THEIR EDUCATIONAL ACTIONS

    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.

  16. Pharmacological ascorbate and ionizing radiation (IR increase labile iron in pancreatic cancer

    Justin C. Moser

    2014-01-01

    Full Text Available Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR. Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice, higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.

  17. Side effect of acting on the world: Acquisition of action-outcome statistic relation alters visual interpretation of action outcome

    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.

  18. Evaluating Pharmacological Effects of Two Major Components of Shuangdan Oral Liquid: Role of Danshensu and Paeonol in Diabetic Nephropathy Rat.

    Chen, Ying; Liu, Zhuying; Zhou, Fuxing; Zhao, Hang; Yang, Qian; Li, Hua; Sun, Jiyuan; Wang, Siwang

    2016-09-01

    Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms. PMID:27582557

  19. A Review of the Pharmacological Effects of the Dried Root of Polygonum cuspidatum (Hu Zhang and Its Constituents

    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.

  20. PHARMACOLOGICAL SCREENING OF ISOLATED COMPOUND FROM MADHUKA LONGIFOLIA SEEDS GIVES SIGNIFICANT ANALGESIC EFFECT

    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. Maternal and child undernutrition: effective action at national level.

    Bryce, Jennifer; Coitinho, Denise; Darnton-Hill, Ian; Pelletier, David; Pinstrup-Andersen, Per

    2008-02-01

    80% of the world's undernourished children live in just 20 countries. Intensified nutrition action in these countries can lead to achievement of the first Millennium Development Goal (MDG) and greatly increase the chances of achieving goals for child and maternal mortality (MDGs 4 and 5). Despite isolated successes in specific countries or for interventions--eg, iodised salt and vitamin A supplementation--most countries with high rates of undernutrition are failing to reach undernourished mothers and children with effective interventions supported by appropriate policies. This paper reports on an assessment of actions addressing undernutrition in the countries with the highest burden of undernutrition, drawing on systematic reviews and best-practice reports. Seven key challenges for addressing undernutrition at national level are defined and reported on: getting nutrition on the list of priorities, and keeping it there; doing the right things; not doing the wrong things; acting at scale; reaching those in need; data-based decisionmaking; and building strategic and operational capacity. Interventions with proven effectiveness that are selected by countries should be rapidly implemented at scale. The period from pregnancy to 24 months of age is a crucial window of opportunity for reducing undernutrition and its adverse effects. Programme efforts, as well as monitoring and assessment, should focus on this segment of the continuum of care. Nutrition resources should not be used to support actions unlikely to be effective in the context of country or local realities. Nutrition resources should not be used to support actions that have not been proven to have a direct effect on undernutrition, such as stand-alone growth monitoring or school feeding programmes. In addition to health and nutrition interventions, economic and social policies addressing poverty, trade, and agriculture that have been associated with rapid improvements in nutritional status should be

  2. Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma.

    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. PMID:26763536

  3. Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis

    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.

  4. Comparison of the Pharmacological Effects of Paricalcitol Versus Calcitriol on Secondary Hyperparathyroidism in the Dialysis Population.

    Večerić-Haler, Željka; Romozi, Karmen; Antonič, Manja; Benedik, Miha; Ponikvar, Jadranka Buturović; Ponikvar, Rafael; Knap, Bojan

    2016-06-01

    Management of secondary hyperparathyroidism (SHPT) in dialysis population includes the use of active vitamin D forms, among which paricalcitol was shown to be more effective at reducing parathyroid hormone (PTH) concentrations. A prospective randomized study comparing the effectiveness and safety of peroral paricalcitol and calcitriol in suppressing PTH concentrations in 20 hemodialysis patients was performed comparing the influence of agents on PTH suppression, calcium (Ca) and phosphate (P) level and calcium-phosphorus product (C×P). The study was performed in an "intent to treat" manner with primary end point in reduction of PTH level in the target area of 150 > PTH ng/L after 3 months. At the time point 3 months after therapy induction paricalcitol and calcitriol were equally efficient at correcting PTH levels, with paricalcitol showing significantly less calcemic effect than calcitriol. PMID:27312912

  5. The pharmacological effect of positive KCNQ (Kv7) modulators on dopamine release from striatal slices

    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...... retigabine. Other compounds of the same class but with some preferences for different KCNQ subtypes such as ICA-27243, BMS-204352 and S-(1) were also tested. All three compounds produced a significant effect albeit weaker than retigabine. The potency of ICA-27243 was in the range of retigabine, and with a...

  6. The effective action approach applied to nuclear chiral sigma model

    The nuclear chiral sigma model of nuclear matter is considered by means of the Cornwall-Jackiw-tomboulis (CTJ) effective action. The method provides a very general framework for investigating many important problems: chiral symmetry in nuclear medium, energy density of nuclear ground state, nuclear Schwinger-Dyson (SD) equations, etc. It is shown that the SD equations for sigma-omega mixing are actually not present in this formalism. For numerical computation purposes the Hartree-Fock (HF) approximation for ground state energy density is also presented. (author). 26 refs

  7. Regular effective action of gauge field theory and quantum gravity

    Baaklini, N.S.

    1987-05-15

    We present a perturbative formalism for the effective quantum action of a general Fermi-Bose field theory. We propose a unitary alternative to the conventional virtual ghost prescription for handling the functional integral of gauge fields, based on the functional space metric that is determined by the Dirac brackets of the canonical theory. A gauge-invariant Gaussian cutoff is introduced by extending the functional space metric into a regular counterpart. The regular one-loop contributions of a scalar field to the photon and the graviton self-energies are computed. The otherwise logarithmically divergent contributions are found, in our scheme, to be independent of cutoff.

  8. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

    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.

  9. Cognitive-Behavioral and Pharmacological Interventions for Hyperactive Boys: Comparative and Combined Effects.

    Hinshaw, Stephen P.; And Others

    1984-01-01

    Assessed the effects of two interventions on hyperactive children's (N=24) social behavior. Results indicated that both methylphenidate (Ritalin) and reinforced self-evaluation were superior to the contrast treatments. Medication plus cognitive-behavioral self-evaluation proved optimal, and placebo plus reinforcement alone was significantly worse…

  10. Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice

    Kjellev, Stine; Thim, Lars; Pyke, Charles;

    2007-01-01

    effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma...

  11. [Pharmacological and pharmacokinetic features and clinical effects of pitavastatin (Livalo Tablet)].

    Yamazaki, Hiroyuki; Fujino, Hideki; Kanazawa, Mizuho; Tamaki, Taro; Sato, Fumiyasu; Suzuki, Mikio; Kitahara, Masaki

    2004-05-01

    Today 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most often prescribed drugs among the therapeutics for hypercholesterolemia. Pitavastatin is a novel statin that has been developed entirely in Japan from the biological screening to clinical studies persuing more efficatious statin than hitherto known. Preclinical studies on drug metabolism revealed that pitavastatin is distributed selectively to the liver, excreted into bile without metabolic modification, and efficiently re-circulates to the liver to show a prolonged plasma half-life. In guinea pigs, pitavastatin enhanced hepatic LDL receptor activity and reduced VLDL secretion in a liver perfusion study, and it lowered plasma total cholesterol (TC) levels at 0.3 mg/kg and triglyceride (TG) levels at 1 mg/kg, respectively, and more. From these results, pitavastatin is assumed to lower LDL cholesterol (LDL-C) by promoting LDL receptor expression and further potentiate the cholesterol-lowering effect and exert TG-lowering effect by reducing VLDL secretion. (14)C-Pitavastatin is metabolized with CYP2C9 to 8-hydroxy derivative, but its Vmax /Km was about 2 micro l/min/mg, about 1/8 to 1/100 in comparison to the reported values of other statins, indicating that pitavastatin is hardly metabolized. Also, other human P450 species were not inhibited by pitavastatin. Therefore, pitavastatin is considered to have little interaction with drugs through P450. In the summarized clinical results with 862 patients, pitavastatin lowered TC and LDL-C by 28% and 40%, respectively. There was no difference in the frequency of side effects and no serious adverse effect was observed for pitavastatin. Pitavastatin possesses superior plasma lipid-improving effects, induces little drug interaction, and is expected to make a good contribution to the medication of hypercholesterolemia. PMID:15118259

  12. Pharmacology and toxicology of sensitizers: mechanism studies

    Nitroimidazoles are being studied extensively as hypoxic cell radiosensitizers. Besides their ability to selectively sensitize hypoxic cells to radiation, which depends on the parent compound, nitroimidazoles have a variety of other effects in vitro, in vivo and clinically which appear to require reductive metabolism. As a first step to suggesting possible mechanisms for these other biological effects, a summary has been made of the known oxidative and reductive products of the two most widely studied radiosensitizers, metronidazole and misonidazole. As a second step to suggesting possible mechanisms for these biological effects, it is important to view the problem in terms of the in vivo situation where distribution and sites of metabolism of the drug and its reduction products will be important factors. Combining basic information about the reduction chemistry of nitroimidazoles with knowledge about the pharmacology of drugs and their reduced products should allow a better assessment of mechanism of action as well as a better implementation of these drugs clinically

  13. Effective action for the Regge processes in gravity

    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.)

  14. Effects of pharmacological serum from normal and liver fibrotic rats on HSCs

    Xi-Xian Yao; Tao Lv

    2005-01-01

    AIM: To make drug sera of Salvia miltiorrhiza and Yigankang, both of which are Chinese herbs that activate bleeding and eliminate stasis, in normal rats and those with liver fibrosis, respectively. To investigate and compare the effects of the two different drug sera on the proliferation and activation of hepatic stellate cells (HSCs).METHODS: Some rats were induced with liver fibrosis:40% carbon tetrachloride (CCl4) subcutaneous injection,twice a week for 9 wk. Salvia miltiorrhiza, Yigankang,colchicines and normal saline were administered into the stomachs of normal rats and those with liver fibrosis.Drug sera were extracted 5 d later. HSCs in vitro were cultivated in different drug sera for 24 h. The rates of proliferation and expression of α-smooth muscle actin (α-SMA) were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry stain, respectively.RESULTS: The drug sera from normal and liver fibrotic rats could be used to cultivate HSCs and to observe the effects of the corresponding components of herbs on HSCs. Salvia miltiorrhiza and Yigankang had better inhibitory effects on HSCs than colchicines (MTT: normal drug serum: Salvia miltiorrhiza 0.42±0.08, Yigankang 0.32±0.10 vs colchicines 0.45±0.12 pathological drug serum: Salvia miltiorrhiza 0.33±0.02, Yigankang 0.26±0.01vs colchicines 0.41±0.09. P<0.05). The drug sera of Salvia miltiorrhiza, Yigankang from liver fibrotic rats had a stronger inhibitory effect than the same ones from normal rats (MTT: Salvia miltiorrhiza: normal drug serum 0.42±0.08 vs pathological drug serum 0.33±0.02. Yigankang: normal drug serum 0.32±0.10 vs pathological drug serum 0.26±0.01.P<0.05).CONCLUSION: Salvia miltiorrhiza and Yigankang could inhibit the expression of α-SMA and the proliferation of HSCs. The drug sera from normal and liver fibrotic rats had different effects on HSCs, probably due to different metabolic processes, effective components and different

  15. Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

    Chung Man Chin

    2012-11-01

    Full Text Available Long-term nonsteroidal anti-inflammatory drugs (NSAIDs therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenylindolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE2 levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.

  16. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    This chapter describes the displacement of 3H-23390 and 3H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3H-SCH 23390 and 3H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  17. Effect of speech therapy and pharmacological treatment in prosody of parkinsonians

    Luciana Lemos de Azevedo

    2015-01-01

    Full Text Available Objective Parkinsonian patients usually present speech impairment. The aim of this study was to verify the influence of levodopa and of the adapted Lee Silverman Vocal Treatment® method on prosodic parameters employed by parkinsonian patients. Method Ten patients with idiopathic Parkinson's disease using levodopa underwent recording of utterances produced in four stages: expressing attitudes of certainty and doubt and declarative and interrogative modalities. The sentences were recorded under the effect of levodopa (on, without the effect of levodopa (off; before and after speech therapy during the on and off periods. Results The speech therapy and its association with drug treatment promoted the improvement of prosodic parameters: increase of fundamental frequency measures, reduction of measures of duration and greater intensity. Conclusion The association of speech therapy to medication treatment is of great value in improving the communication of parkinsonian patients.

  18. Pharmacological Selectivity Within Class I Histone Deacetylases Predicts Effects on Synaptic Function and Memory Rescue.

    Rumbaugh, Gavin; Sillivan, Stephanie E; Ozkan, Emin D; Rojas, Camilo S; Hubbs, Christopher R; Aceti, Massimiliano; Kilgore, Mark; Kudugunti, Shashi; Puthanveettil, Sathyanarayanan V; Sweatt, J David; Rusche, James; Miller, Courtney A

    2015-09-01

    Histone deacetylases (HDACs) are promising therapeutic targets for neurological and psychiatric disorders that impact cognitive ability, but the relationship between various HDAC isoforms and cognitive improvement is poorly understood, particularly in mouse models of memory impairment. A goal shared by many is to develop HDAC inhibitors with increased isoform selectivity in order to reduce unwanted side effects, while retaining procognitive effects. However, studies addressing this tack at the molecular, cellular and behavioral level are limited. Therefore, we interrogated the biological effects of class I HDAC inhibitors with varying selectivity and assessed a subset of these compounds for their ability to regulate transcriptional activity, synaptic function and memory. The HDAC-1, -2, and -3 inhibitors, RGFP963 and RGFP968, were most effective at stimulating synaptogenesis, while the selective HDAC3 inhibitor, RGFP966, with known memory enhancing abilities, had minimal impact. Furthermore, RGFP963 increased hippocampal spine density, while HDAC3 inhibition was ineffective. Genome-wide gene expression analysis by RNA sequencing indicated that RGFP963 and RGFP966 induce largely distinct transcriptional profiles in the dorsal hippocampus of mature mice. The results of bioinformatic analyses were consistent with RGFP963 inducing a transcriptional program that enhances synaptic efficacy. Finally, RGFP963, but not RGFP966, rescued memory in a mouse model of Alzheimer's Disease. Together, these studies suggest that the specific memory promoting properties of class I HDAC inhibitors may depend on isoform selectivity and that certain pathological brain states may be more receptive to HDAC inhibitors that improve network function by enhancing synapse efficacy. PMID:25837283

  19. Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model

    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 an...

  20. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium

    Chieh-fu CHEN; Wen-fei CHIOU; Jun-tian ZHANG

    2008-01-01

    Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic" around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive compo-nents contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For antican-cer effects, P quinquefolium is better.

  1. [Effect of some pharmacological substances on the motility of the Cryptocotyle lingua cercaria (Heterophyidae)].

    Tolstenkov, O O; Prokof'ev, V V; Terenina, N B; Galaktionov, K V

    2010-01-01

    The effect of some biologically active substances (acetylcholine, serotonin, octopamine, sodium nitroprussid and FMRF-amide) on the motility of the Cryptocotyle lingua cercariae was studied. Solutions of FMRF-amide, octopamine, and sodium nitroprussid have no statistically significant influence on the motility of C. lingua. Acetylcholine and serotonin in solutions affected the motility through the prolongation of the active phase of swimming. Further research is required to elucidate the mechanisms underlying the cercarial motility. PMID:21061596

  2. Microcirculation of chronic venous disease: Role of leucocyte-endothelial activation and effects of pharmacological intervention.

    Howlader, M. H.

    2004-01-01

    Many theories have been advanced to explain the development of venous ulceration in the lower limb. In recent years, the hypothesis of inappropriate leucocyte activation with the release of free radicals causing damage to the microcirculation in patients with CVD has gained popularity. No drug has so far been found to ameliorate these effects. In this thesis I have investigated a series of inflammatory markers in patients with various CEAP stages of venous disease. The aim was to asses which,...

  3. Effect of Protein Binding on the Pharmacological Activity of Highly Bound Antibiotics▿

    Schmidt, Stephan; Röck, Katharina; Sahre, Martina; Burkhardt, Olaf; Brunner, Martin; Lobmeyer, Maximilian T.; Derendorf, Hartmut

    2008-01-01

    During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used ...

  4. New insights into dietary supplements used in sport: active substances, pharmacological and side effects.

    Koncic, Marijana Zovko; Tomczyk, Michal

    2013-08-01

    As a society we are increasingly concerned about our physical appearance. For example, as much as 24% of people in developed countries admittedly exercise to improve their performance. Professional sportsmen and amateurs alike are in a constant search for new means that will enable them better sport results in shorter time. Among those means, a prominent place belongs to dietary supplements. However, the producers often advertise products whose use in sports is neither scientifically founded nor safe. This brings on an irrational use of herbal supplements which sometimes leads to unwanted side effects, but is more often of little use. Thus, the aim of this review will be to systematically evaluate some of the herbal supplements that are used as adaptogenic and ergogenic aids in sport. The review will include available data on Rhodiola rosea, Withania somnifera, Schisandra chinensis, Tribulus terrestris, Vitis vinifera, Citrus aurantium, and others. Their effects, active ingredients as well as possible adverse effects will be discussed with special focus on clinical studies. PMID:23574283

  5. In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

    A Jalali

    2011-01-01

    Full Text Available The available Razi Institute antivenom is still, empirically, used by intramuscular (IM administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus. The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH following H. lepturus sting. Simultaneous intramuscular administration of 10 μL and 100 μL of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC count and hemoglobin were observed. Immediate intramuscular administration of 10 μL of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.

  6. Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia.

    Herrera-Ruiz, M; Zamilpa, A; González-Cortazar, M; Reyes-Chilpa, R; León, E; García, M P; Tortoriello, J; Huerta-Reyes, M

    2011-11-15

    Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg. PMID:21788126

  7. Pharmacological Correction of the Negative Effect of Acetylsalicylic Acid on the Energy-Generating System

    Vladimir V. Udut, ScD

    2012-03-01

    Full Text Available The present paper demonstrates the effect of ASA and its combination with SUC on the energy-producing system of rat heart mitochondria as well as an assessment of SUC preventive application effect on ASA pharmacokinetic parameters. Experiments conducted on outbred male albino rats (200-250 g on a model of a xenobiotic load induced by seven days of intragastric injections of acetylsalicylic acid at a dose of 250 mg/kg have shown inhibition of the oxygen consumption rates in the heart mitochondria as well as a limitation of the succinate-dependent substrate oxidation pathways and a decrease in the mitochondria ATP/ADP coefficient. Succinic acid (50 mg/kg for 7 days was injected as a preventive medication to correct the mitochondrial bioenergetics revealed. A comparative research of the pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinic acid performed on the model of rabbits has shown total similarity in the parameters analyzed. This fact demonstrates the possibility of prevention of mitochondrial dysfunction using the intermediate Krebs cycle. SUC as preventive medication promotes the elimination of ASA-induced negative metabolic shifts in the rat heart mitochondria by normalizing the succinate- and NAD-dependent respiration, oxidative phosphorylation, and therefore, it finds good use in the correction of ASA-induced negative side-effects of an energy-generating system

  8. 观辣树药理作用研究进展%Pharmacological effects of Moringa oleifera: research advances

    舒畅; 刘俊珊; 张冬梅; 李振清; 卢艳仪; 朱文婷; 叶文才

    2011-01-01

    观辣树(Morlnga oleifera)原产于非洲及印度,近年来在我国广东、云南、海南等地开始大量引种.在民间,观辣树不仅作为食物,也可作为药物用于发热、高血压、溃疡以及皮肤感染等疾病的治疗.现代研究表明,观辣树具有抑菌、抗炎、保肝、抗肿瘤和预防心血管疾病等多种药理活性.本文综述近年来观辣树的药理作用研究进展,以期为该植物的进一步开发利用提供参考.%Moringa oleifera was originated in Mrica and India. In recent years, it has been widely planted in Guangdong,Yunnan and Hainan provinces in China. Moringa oleifera can be used not only as food, but also as drug to treat fever, hypertension, ulcer and skin infection. Recent studies demonstrated its various bioactivities such as anti-bacterial, anti-inflammatory, hepatoprotecfive, anti-tumor, hypolipemia activities and so on. This paper mainly reviews the research progress in the pharmacological effects of Moringa oleifera, aiming to provide information helpful for its further pharmaceutical application.

  9. Clinical pharmacology and malaria.

    Breckenridge, A M; Winstanley, P A

    1997-10-01

    The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs. PMID:9625927

  10. Differential pharmacological effects on brain reactivity and plasticity in Alzheimer’s Disease

    Anna-Katharine eBrem

    2013-10-01

    Full Text Available Acetylcholinesterase inhibitors (AChEI are the most commonly prescribed monotherapeutic medications for Alzheimer’s disease (AD. However, their underlying neurophysiological effects remain largely unknown.We investigated the effects of monotherapy (AChEI and combination therapy (AChEI and memantine on brain reactivity and plasticity. Patients treated with monotherapy (AChEI (N=7 were compared to patients receiving combination therapy (COM (N=9 and a group of age-matched, healthy controls (HC (N=13. Cortical reactivity and plasticity of the motor cortex (MC were examined using transcranial magnetic stimulation (TMS. Cognitive functions were assessed with the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog, activities of daily living with the ADCS-ADL. In addition we assessed the degree of brain atrophy by measuring brain-scalp distances in seven different brain areas.Patient groups differed in resting motor threshold and brain atrophy, with COM showing a lower motor threshold but less atrophy than AChEI. COM showed similar plasticity effects as the HC group, while plasticity was reduced in AChEI. Long-interval intracortical inhibition (LICI was impaired in both patient groups when compared to HC. ADAS-Cog scores were positively correlated with LICI measures and with brain atrophy, specifically in the left IPL.AD patients treated with mono- or combination therapy show distinct neurophysiological patterns. Further studies should investigate whether these measures might serve as biomarkers of treatment response and whether they could guide other therapeutic interventions.

  11. Flupirtine: Clinical pharmacology.

    Harish, S; Bhuvana, K; Bengalorkar, Girish M; Kumar, Tn

    2012-04-01

    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. PMID:22557738

  12. Flupirtine: Clinical pharmacology

    Harish, S; K Bhuvana; Girish M Bengalorkar; T N Kumar

    2012-01-01

    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 wit...

  13. Flupirtine : Clinical pharmacology

    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.

  14. Adverse Effects in the Pharmacologic Management of Bipolar Disorder During Pregnancy.

    Hogan, Charlotte S; Freeman, Marlene P

    2016-09-01

    Management of bipolar disorder during pregnancy often involves medications with potential adverse effects, including risks to the mother and fetus. Although some specifics are known, many medications continue to have incompletely characterized reproductive safety profiles. Women with bipolar disorder who are planning pregnancy face challenging decisions about their treatment; careful risk-benefit discussions are necessary. With the goal of further informing these discussions, this article reviews the data currently available regarding medication safety in the management of bipolar disorder during pregnancy, with specific attention to lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic medications. PMID:27514299

  15. Research progress on Chemical composition and pharmacological effects of pomegranate%石榴化学成分及其药理作用研究进展

    闫恒; 张辉

    2016-01-01

    石榴含有多种化学成分,包括多酚类、脂肪酸、黄酮类、生物碱、多糖、鞣质、糖类、有机酸、维生素、微量元素等,其药理活性主要有降糖、降血脂、降血压、抗病毒、抗微生物、保护肝脏损伤、抗疲劳等。随着研究石榴的力度不断加大,对其药理作用机制会更加清晰。本文对石榴化学成分和药理作用两个方面进行综述,为石榴的进一步研究和开发应用提供参考。%Pomegranate contained a variety of chemical composition, including polyphenols, fatty acid, flavonoids, alkaloids, polysaccharides, tannins, sugars, organic acids, vitamins, trace elements, such as pharmacological activities mainly included sugar, fall hematic fat, fall blood pressure, antiviral, antimicrobial, protect liver damage, fatigue resistance, etc. Along with the continuously increased, the magnitude of the pomegranate research will eventually the chemical composition of excavated from it more, its pharmacological action mechanism will be more clear. In this paper, two aspects of chemical composition and pharmacological action of pomegranate were reviewed to provide a reference for further research and development and application of the pomegranate.

  16. Experimental pharmacological investigation of the antiarthrotic effects of the cartilage and bone marrow extract Rumalon

    Kalbhen, D.A.

    1981-08-05

    On the basis of animal experiments, the authors have developed a model of arthrosis which is compatible in its radiological, macroscopic, biochemical, and histological aspects with the pathophysiology of human arthrosis and has been tried in the testing of the antiarthrotic properties of pharmaceuticals. Biochemically induced gonarthroses of experimental animals were used for studies of the effects of a cartilage and bone marrow extract (Rumalon) and a cartilage extract and its high-molecular component DAK-16 on the frequency and progression of degenerative joint diseases. As test parameters, measurements of the articular space, X-ray findings, and macroscopic findings were quantitatively evaluated. The animal experiments show that the inhibitive effects of steroidal and nonsteroidal antirheumatics on the synthesis of the cartilage matrix can be prevented or reduced by simultaneous administration of chondroprotective pharmaceuticals; this may be important on the clinical sector. This antagonism between antiphlogistic agents and Rumalon, which has been observed also in fibroblast cultures and wound healing experiments, is of interest especially for the treatment of activated arthroses.

  17. Experimental pharmacological investigation of the antiarthrotic effects of the cartilage and bone marrow extract Rumalon

    On the basis of animal experiments, the authors have developed a model of arthrosis which is compatible in its radiological, macroscopic, biochemical, and histological aspects with the pathophysiology of human arthrosis and has been tried in the testing of the antiarthrotic properties of pharmaceuticals. Biochemically induced gonarthroses of experimental animals were used for studies of the effects of a cartilage and bone marrow extract (Rumalon) and a cartilage extract and its high-molecular component DAK-16 on the frequency and progression of degenerative joint diseases. As test parameters, measurements of the articular space, X-ray findings, and macroscopic findings were quantitatively evaluated. The animal experiments show that the inhibitive effects of steroidal and nonsteroidal antirheumatics on the synthesis of the cartilage matrix can be prevented or reduced by simultaneous administration of chondroprotective pharmaceuticals; this may be important on the clinical sector. This antagonism between antiphlogistic agents and Rumalon, which has been observed also in fibroblast cultures and wound healing experiments, is of interest especially for the treatment of activated arthroses. (orig./MG)

  18. Pharmacognostical, phytochemical and pharmacological evaluation for the antipyretic effect of the seeds of Saraca asoca Roxb.

    Sasmal S; Majumdar S; Gupta M; Mukherjee A; Mukherjee PK

    2012-01-01

    To conduct a systemic evaluation of the medicinal value of seeds which include macroscopic and microscopic characterization, physiochemical evaluation, preliminary phytochemical screening and experimental antipyretic activity. Methods: Saraca asoca seed was studied for pharmacognostical, phytochemical and other recommended methods for standardizations. Also, the acetone extract of the seeds was evaluated for acute toxicity study and antipyretic activity using Brewer’s yeast induced pyrexia in Wistar rats at oral doses of 300 mg/kg and 500 mg/kg. Results: After phytochemical screening, the acetone extract showed the presence of saponin, tannins and flavonoids which inhibit pyrexia. The therapeutic efficacy achieved at both the dose levels of the research drug and standard drug aspirin (100 mg/kg) showed significant (P<0.01) antipyretic activity when compared to the control group. The highly significant antipyretic effect exhibited at the dose of 500 mg/kg was also found to be sustainable in nature.Conclusions:The antipyretic effect of the acetone extract showed significant results in rats at the dose of 500 mg/kg after following the standard pharmacognostical and phytochemical methods.

  19. Effective corrective actions to enhance operational safety of nuclear installations

    The safe operation of nuclear power plants around the world and the prevention of incidents in these installations remain key concerns for the nuclear community. In this connection the feedback of operating experience plays a major role: every nuclear plant operator needs to have a system in place to identify and feed back the lessons learned from operating experience and to implement effective corrective actions to prevent safety events from reoccurring. An effective operating experience programme also includes a proactive approach that is aimed at preventing the first-time occurrence of safety events. In April 2003, the IAEA issued the PROSPER guidelines for nuclear installations to strengthen and enhance their own operating experience process and for self-assessment on the effectiveness of the feedback process. Subsequently, in the course of the Operational Safety Review Teams missions conducted by the IAEA that focused on the operational safety practices of nuclear power plants, the IAEA enhanced the review of the operating experience in nuclear power plants by implementing a new module that is derived from these guidelines. In order to highlight the effective implementation of the operating experience programme and to provide practical assistance in this area, the IAEA organized workshops and conferences to discuss recent trends in operating experience. The IAEA also performed assistance and review missions at plants and corporate organizations. The IAEA is further developing advice and assistance on operating experience feedback programmes and is reporting on good practices. The present publication is the outcome of two years of coordinated effort involving the participation of experts of nuclear organizations in several Member States. It provides information and good practices for successfully establishing an effective corrective actions programme. This publication forms part of a series that develops the principles set forth in these guidelines

  20. Modulatory Effects and Action Mechanisms of Tryptanthrin on Murine Myeloid Leukemia Cells

    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.

  1. The Effect of Temperature on Pressurised Hot Water Extraction of Pharmacologically Important Metabolites as Analysed by UPLC-qTOF-MS and PCA.

    Khoza, B S; Chimuka, L; Mukwevho, E; Steenkamp, P A; Madala, N E

    2014-01-01

    Metabolite extraction methods have been shown to be a critical consideration for pharmacometabolomics studies and, as such, optimization and development of new extraction methods are crucial. In the current study, an organic solvent-free method, namely, pressurised hot water extraction (PHWE), was used to extract pharmacologically important metabolites from dried Moringa oleifera leaves. Here, the temperature of the extraction solvent (pure water) was altered while keeping other factors constant using a homemade PHWE system. Samples extracted at different temperatures (50, 100, and 150°C) were assayed for antioxidant activities and the effect of the temperature on the extraction process was evaluated. The samples were further analysed by mass spectrometry to elucidate their metabolite compositions. Principal component analysis (PCA) evaluation of the UPLC-MS data showed distinctive differential metabolite patterns. Here, temperature changes during PHWE were shown to affect the levels of metabolites with known pharmacological activities, such as chlorogenic acids and flavonoids. Our overall findings suggest that, if not well optimised, the extraction temperature could compromise the "pharmacological potency" of the extracts. The use of MS in combination with PCA was furthermore shown to be an excellent approach to evaluate the quality and content of pharmacologically important extracts. PMID:25371697

  2. The Effect of Temperature on Pressurised Hot Water Extraction of Pharmacologically Important Metabolites as Analysed by UPLC-qTOF-MS and PCA

    B. S. Khoza

    2014-01-01

    Full Text Available Metabolite extraction methods have been shown to be a critical consideration for pharmacometabolomics studies and, as such, optimization and development of new extraction methods are crucial. In the current study, an organic solvent-free method, namely, pressurised hot water extraction (PHWE, was used to extract pharmacologically important metabolites from dried Moringa oleifera leaves. Here, the temperature of the extraction solvent (pure water was altered while keeping other factors constant using a homemade PHWE system. Samples extracted at different temperatures (50, 100, and 150°C were assayed for antioxidant activities and the effect of the temperature on the extraction process was evaluated. The samples were further analysed by mass spectrometry to elucidate their metabolite compositions. Principal component analysis (PCA evaluation of the UPLC-MS data showed distinctive differential metabolite patterns. Here, temperature changes during PHWE were shown to affect the levels of metabolites with known pharmacological activities, such as chlorogenic acids and flavonoids. Our overall findings suggest that, if not well optimised, the extraction temperature could compromise the “pharmacological potency” of the extracts. The use of MS in combination with PCA was furthermore shown to be an excellent approach to evaluate the quality and content of pharmacologically important extracts.

  3. 蜂毒的主要成分及药理作用的研究进展%Advances in main compositions and pharmacological effects of bee venom

    张冰清; 刘晓波

    2016-01-01

    Bee venom is a kind of active compounds secreted by the gland,which have many active ingredients like anti-inflammatory,anti -tumor,analgesic,anti -hypertensive and so on.In recent years,many scientists had been made im-portant progress in research of the active ingredient analysis,genetic structure,pharmacological action mechanism and mo-lecular biology of bee venom.The purpose of this article was to summarize main active ingredients of bee venom and the main pharmacological actions and provide theoretical basis for the clinical used.%蜂毒是由蜜蜂毒腺分泌的活性物质,其中很多活性成分具有抗炎、抗肿瘤、镇痛、降压的作用。近年来,国内外很多科学家对蜂毒的活性成分及其基因结构、药理作用机制、分子生物学等方面进行了研究,并且取得了重要的研究进展。本文总结了蜂毒的主要活性成分以及主要的药理作用,为蜂毒的临床应用提供理论基础。

  4. Differential effects comparing exercise and pharmacologic stress on left ventricular function using gated Tc-99m sestamibi SPECT

    Although post-ischemic stunning has emerged as an important marker for severe coronary artery disease (CAD), differences in stress methods may have different effects on left ventricular (LV) volumes and function. To assess differential effects comparing exercise and pharmacologic stress on the LV measurements, 99mTc-sestamibi gated single-photon emission computed tomography (SPECT) acquired more than 30 min after stress and at rest was evaluated in 38 patients undergoing adenosine triphosphate (ATP) stress (ATP group) and 38 age- and sex-matched patients subjected to exercise stress (Ex group) among 268 patients with normal SPECT findings. Coronary risk factors and LV volumetric measurements at baseline were similar in the two groups. Compared with volumetric measurements at rest, end-diastolic volume (EDV) increased (72±21 ml to 74±21 ml; P=0.01), end-systolic volume increased (25±12 ml to 28±13 ml; P=0.001), and ejection fraction (EF) decreased after stress (66%±8% to 63%±9%; P<0.002) in the ATP group. In the Ex group, by contrast, no such change was observed. In addition, changes in EDV (3±6 vs. -1±5 ml; P=0.01) and the stress-to-rest ratio of EDV (1.04±0.09 vs. 0.99±0.08; P<0.02) after stress were greater in the ATP than in the Ex group. Differential effects of stress methods on LV volumes persist more than 30 min after the stress. These findings should be kept in mind when interpreting post-ischemic stunning. (author)

  5. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. PMID:26936802

  6. Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model.

    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.

  7. Effective Action for Cosmological Scalar Fields at Finite Temperature

    Cheung, Yeuk-Kwan E; Kang, Jin U; Kim, Jong Chol

    2015-01-01

    Scalar fields appear in many theories beyond the Standard Model of particle physics. In the early universe, they are exposed to extreme conditions, including high temperature and rapid cosmic expansion. Understanding their behavior in this environment is crucial to understand the implications for cosmology. We calculate the finite temperature effective action for the field expectation value in two particularly important cases, for damped oscillations near the ground state and for scalar fields with a flat potential. We find that the behavior in both cases can in good approximation be described by a complex valued effective potential that yields Markovian equations of motion. Near the potential minimum, we recover the solution to the well-known Langevin equation. For large field values we find a very different behavior, and our result for the damping coefficient significantly differs from the expressions given in the literature. We illustrate our results in a simple scalar model, for which we give analytic app...

  8. Neutrophilic superoxide production can assess pharmacological and pharmacogenetic β-adrenoreceptor effects.

    Reinartz, M T; Wetzke, M; Happle, C; Kälble, S; Scherer, R; Kabesch, M; Seifert, R

    2016-08-01

    Asthma can be controlled well in most patients by inhaled β-adrenoreceptor (β2 AR) agonists and steroids. Poor response to β2 AR agonists is difficult to predict, especially in young children and by lung function testing, which may be affected by multiple influences. As an alternative approach, we analyzed ex vivo neutrophilic superoxide inhibition in response to β2 AR stimulation. In 60 healthy volunteers, this assay was unaffected by sex, age, smoking, atopy or asthma status. Furthermore, we assessed effects of genetic variants in β2 AR by sequencing the ADRB2 gene in our cohort and relating genotypes to β2 AR-mediated neutrophilic superoxide inhibition. Gly16Arg genotypes correlated with minor decrease in overall adrenoresponse in this small study population. Taken together, ex vivo testing of the β2 AR response in human neutrophils represents a robust tool with good signal-to-noise ratio at physiological β2 AR agonist concentrations, and this assay may be useful to complement future pharmacogenetic studies in asthma. PMID:27091647

  9. Effects of pharmacological block of GABAA receptors on pallidal neurons in normal and parkinsonian state

    Yan Xue

    2010-02-01

    Full Text Available The globus pallidus plays a central integrative role in the basal ganglia circuitry. Morphological studies have revealed a high level of GABA and GABAA receptors in the globus pallidus. To further investigate the effects of endogenous GABAA neurotransmission in the globus pallidus of normal and parkinsonian rats, in vivo extracellular recording and behavioral tests were performed in the present studies. In normal rats, micro-pressure ejection of GABAA receptor antagonist gabazine (0.1 mM increased the spontaneous firing rate of pallidal neurons by 28.3%. Furthermore, in 6-hydroxydopamine parkinsonian rats, gabazine increased the firing rate by 46.0% on the lesioned side, which was significantly greater than that on the unlesioned side (21.5%, P<0.05, as well as that in normal rats (P<0.05. In the behaving rats, unilateral microinjection of gabazine (0.1 mM evoked consistent contralateral rotation in normal rats, and significantly potentiated the number of apomorphine-induced contralateral rotations in parkinsonian rats. The present electrophysiological and behavioral findings may provide a rational for further investigations into the potential of pallidal endogenous GABAA neurotransmission in the treatment of Parkinson’s disease.

  10. EFFECTS OF PHARMACOLOGY WITH ACEPROMAZINE MALEATE IN TRANQUILIZATION, HEMATOLOGY AND VITAL PARAMETERS IN CATS

    L. F. Tannus

    2016-02-01

    Full Text Available This work aims to evaluate the tranquilization, the hematological and the physiological parameters of domestic cats undergoing pharmacupuncture with acepromazine maleate. Seven animals received 5% of the dose of the drug indicated for this species in acupoint Yintang (GI and seven (GII received the same dose intramuscularly. The reassurance was assessed using a scale adapted from Dobbins et al. (2002. The GI group demonstrated that 71.43% of the animals presented drowsiness and projection of the third eyelid and 28.47% were less active. In GII group, 14.28% of cats were less active and 85.72% demonstrated were unchanged. About the hematologicals changing, the two groups demonstrated a slight increase of leukocytes, in GI decreased hematocrit and erythrocytes. According to physiological parameters, GI presented decrease rectal temperature and increase in respiratory rate. There were no significant changes on the heart rate and systolic blood pressure in any cat. In GII, occurred a decrease in diastolic blood pressure. The pharmacupunture showed effectiveness in cats tranquilization, besides clinical safety

  11. Pinocembrin: A Novel Natural Compound with Versatile Pharmacological and Biological Activities

    Azhar Rasul

    2013-01-01

    Full Text Available Pinocembrin (5,7-dihydroxyflavanone is one of the primary flavonoids isolated from the variety of plants, mainly from Pinus heartwood, Eucalyptus, Populus, Euphorbia, and Sparattosperma leucanthum, in the diverse flora and purified by various chromatographic techniques. Pinocembrin is a major flavonoid molecule incorporated as multifunctional in the pharmaceutical industry. Its vast range of pharmacological activities has been well researched including antimicrobial, anti-inflammatory, antioxidant, and anticancer activities. In addition, pinocembrin can be used as neuroprotective against cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antiexcitotoxic effects. Pinocembrin exhibits pharmacological effects on almost all systems, and our aim is to review the pharmacological and therapeutic applications of pinocembrin with specific emphasis on mechanisms of actions. The design of new drugs based on the pharmacological effects of pinocembrin could be beneficial. This review suggests that pinocembrin is a potentially promising pharmacological candidate, but additional studies and clinical trials are required to determine its specific intracellular sites of action and derivative targets in order to fully understand the mechanism of its anti-inflammatory, anticancer, and apoptotic effects to further validate its medical applications.

  12. Pharmacological Properties of Protocatechuic Acid and Its Potential Roles as Complementary Medicine

    Yoswaris Semaming

    2015-01-01

    Full Text Available This paper reviews the reported pharmacological properties of protocatechuic acid (PCA, 3,4-dihydroxy benzoic acid, a type of phenolic acid found in many food plants such as olives and white grapes. PCA is a major metabolite of anthocyanin. The pharmacological actions of PCA have been shown to include strong in vitro and in vivo antioxidant activity. In in vivo experiments using rats and mice, PCA has been shown to exert anti-inflammatory as well as antihyperglycemic and antiapoptotic activities. Furthermore, PCA has been shown to inhibit chemical carcinogenesis and exert proapoptotic and antiproliferative effects in different cancerous tissues. Moreover, in vitro studies have shown PCA to have antimicrobial activities and also to exert synergistic interaction with some antibiotics against resistant pathogens. This review aims to comprehensively summarize the pharmacological properties of PCA reported to date with an emphasis on its biological properties and mechanisms of action which could be therapeutically useful in a clinical setting.

  13. Pharmacological actions of Y-24180, a new specific antagonist of platelet activating factor (PAF): II. Interactions with PAF and benzodiazepine receptors.

    Takehara, S; Mikashima, H; Muramoto, Y; Terasawa, M; Setoguchi, M; Tahara, T

    1990-12-01

    The inhibitory effect of Y-24180, 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-t hieno [3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine, on platelet activating factor (PAF)-induced platelet aggregation and the specific binding of 3H-PAF to platelets was compared with other thienodiazepine derivatives, WEB 2086 and etizolam. Y-24180 inhibited PAF-induced rabbit platelet aggregation in vitro (IC50 3.84 nM), but had little effect on adenosine diphosphate- or arachidonic acid-induced aggregation. WEB 2086 and etizolam also showed an inhibitory effect of PAF-induced aggregation (IC50 values are 456 and 6730 nM, respectively). In PAF-induced human platelet aggregation, Y-24180 (IC50 0.84 nM) was more potent than WEB 2086 (IC50 4.21 nM) and etizolam (IC50 998 nM). Y-24180, WEB 2086 and etizolam displaced 3H-PAF binding from the washed-platelets of rabbits with an IC50 value of 3.50, 9.35 and 29.5 nM, respectively. In rabbits, pretreatment with Y-24180 and WEB 2086 antagonized PAF-induced platelet aggregation dose-dependently. The significant inhibitory effect of Y-24180 (1 mg/kg, p.o.) lasted 72 hr after a single dose oral administration. WEB 2086 (10 mg/kg, p.o.) also antagonized the ex vivo response induced by PAF 1 hr after administration, but no significant effect was observed 3 hr after administration. Y-24180 displaced 3H-diazepam binding from the synaptosomal membranes of rat cerebral cortex with a Ki value of 3.68 microM. The affinity of Y-24180 for benzodiazepine(BZP) receptors was lower than those of WEB 2086 and etizolam and was about 1000 times lower than that for PAF receptors in platelets. PMID:1965554

  14. Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

    The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F1α (6-keto-PGF1α; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM22-52, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP8-37, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K+ channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K+ channels), and apamin (Ca2+-activated channel blocker

  15. Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

    Leite, L.N. [Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Gonzaga, N.A. [Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tirapelli, D.P.C.; Tirapelli, L.F. [Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tirapelli, C.R. [Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-08-15

    The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F{sub 1α} (6-keto-PGF{sub 1α}; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM{sub 22-52}, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP{sub 8-37}, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with N{sup G}-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K{sup +} channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K{sup +} channels), and

  16. Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol.

    Witten, Louise; Bastlund, Jesper Frank; Glenthøj, Birte Y; Bundgaard, Christoffer; Steiniger-Brach, Björn; Mørk, Arne; Oranje, Bob

    2016-01-01

    Sensory gating is the brain's ability to filter out irrelevant information before it reaches high levels of conscious processing. In the current study we aimed to investigate the involvement of the noradrenergic and dopaminergic neurotransmitter systems in sensory gating. Furthermore, we investigated cross-species reliability by comparing effects in both healthy humans and rats, while keeping all experimental conditions as similar as possible between the species. The design of the human experiment (n=21) was a double-blind, placebo-controlled, cross-over study where sensory gating was assessed following a dose of either reboxetine (8 mg), haloperidol (2 mg), their combination or placebo at four separate visits. Similarly in the animal experiment sensory gating was assessed in rats, (n=22) following a dose of reboxetine (2 mg/kg), haloperidol (0.08 mg/kg), their combination or placebo. The sensory gating paradigms in both experiments were identical. In humans, we found significantly reduced P50 suppression following separate administration of reboxetine or haloperidol, while their combined administration did not reach statistical significance compared with placebo. In the rats, we found a similar significant reduction of sensory gating (N40) following treatment with haloperidol and the combination of haloperidol and reboxetine, but not with separate reboxetine treatment, compared with placebo. Our study indicates that even when experimental conditions are kept as similar as possible, direct human to rat cross-species translation of pharmacological effects on sensory gating is challenging, which calls for more focussed research in this important translational area. PMID:26129678

  17. Nonlinear N=2 supersymmetry, effective actions and moduli stabilization

    Antoniadis, I. [Department of Physics, CERN - Theory Division, CH-1211 Geneva 23 (Switzerland); Centre de Physique Theorique, UMR du CNRS 7644, Ecole Polytechnique, 91128 Palaiseau (France); Derendinger, J.-P. [Physics Institute, Neuchatel University, Breguet 1, CH-2000 Neuchatel (Switzerland); Maillard, T. [Centre de Physique Theorique, UMR du CNRS 7644, Ecole Polytechnique, 91128 Palaiseau (France)], E-mail: maillard@cpht.polytechnique.fr

    2009-02-11

    Nonlinear supersymmetry is used to compute the general form of the effective D-brane action in type I string theory compactified to four dimensions in the presence of internal magnetic fields. In particular, the scalar potential receives three contributions: (1) a nonlinear part of the D-auxiliary component, associated to the Dirac-Born-Infeld action; (2) a Fayet-Iliopoulos (FI) D-term with a moduli-dependent coefficient; (3) a D-auxiliary independent (but moduli dependent) piece from the D-brane tension. Minimization of this potential leads to three general classes of vacua with moduli stabilization: (i) supersymmetric vacua allowing in general FI terms to be cancelled by non-trivial vacuum expectation values (VEV's) of charged scalar fields; (ii) anti-de Sitter vacua of broken supersymmetry in the presence of a non-critical dilaton potential that can be tuned at arbitrarily weak string coupling; (iii) if the dilaton is fixed in a supersymmetric way by three-form fluxes and in the absence of charged scalar VEV's, one obtains non-supersymmetric vacua with positive vacuum energy.

  18. Dura’s Effect on Securities Class Actions

    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.

  19. Pharmacology of Marihuana (Cannabis sativa)

    Maickel, Roger P.

    1973-01-01

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

  20. Mechanism of Action and Pharmacology of Patiromer, a Nonabsorbed Cross-Linked Polymer That Lowers Serum Potassium Concentration in Patients With Hyperkalemia.

    Li, Lingyun; Harrison, Stephen D; Cope, M Jamie; Park, Craig; Lee, Lawrence; Salaymeh, Faleh; Madsen, Deidre; Benton, Wade W; Berman, Lance; Buysse, Jerry

    2016-09-01

    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

  1. Pharmacological treatment of the benign prostatic hyperplasia

    Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5α-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the aα1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5aα-reductase inhibitors, the aα1-adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an aα1-adrenoceptor antagonist, aα 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product

  2. Study on Pharmacological Effects of Anti-febrile and Cough-remedy Mixtures%止嗽退热合剂主要药理作用研究

    王之梅; 万鹏; 黄崇刚; 张家继

    2011-01-01

    目的 探讨止嗽退热合剂的主要药理作用,为临床用药提供参考。方法 采用小鼠咳嗽试验、大鼠发热试验和小鼠毒性试验,评价止嗽退热合剂的药效性和安全性。结果 止嗽退热合剂能明显延长浓氨水所致小鼠咳嗽的潜伏期,减少咳嗽次数,且能明显抑制角叉菜胶所致的大鼠肛温升高。毒性试验中,止嗽退热合剂给药量是临床成人用量的347.08倍,可使小鼠有倦卧、自发活动减少等现象,但对体质量增长无明显影响,亦无死亡发生。结论止嗽退热合剂有明显的止嗽、退热功效,临床用药安全可靠。%Objective: To explore the main pharmacological effects of anti-febrile and cough-remedy mixtures. Methods:The mouse cough test,the rat fever test and the mouse toxicity test were used to evaluate the drug action and the safety. Results:Being used the anti -fibrile and cough-remedy mixture,the incubation period was prolonged and the frequency was reduced. Meanwhile, the increase of rectal temperature by carrageenan in rat was inhibited by this drug. In the toxicity test,the drug consumption was 347.08 multiples. After this drug,the tired and the spontaneous activity were decreased. However,the body weight increase was not effected obviously. Also, these experiment animals were not dead through these tests. Conclusion: This mixtures has significant effects on cough-remedy and anti-febrile. Clinical medication is safety and reliability.

  3. Covariant computation of effective actions in Horava-Lifshitz gravity

    D'Odorico, Giulio; Saueressig, Frank

    2015-01-01

    We initiate the systematic computation of the heat-kernel coefficients for Laplacian operators obeying anisotropic dispersion relations in curved spacetime. Our results correctly reproduce the limit where isotropy is restored and special anisotropic cases considered previously in the literature. Subsequently, the heat kernel is used to derive the scalar-induced one-loop effective action and beta functions of Horava-Lifshitz gravity. We identify the Gaussian fixed point which is supposed to provide the UV completion of the theory. In the present setting, this fixed point acts as an infrared attractor for the renormalization group flow of Newton's constant and the high-energy phase of the theory is screened by a Landau pole. We comment on the consequences of these findings for the renormalizability of the theory.

  4. Effective action and vacuum expectations in nonlinear $\\sigma$ model

    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.

  5. [NKT cells: their development, mechanisms and effects of action].

    Bojarska-Junak, Agnieszka; Tabarkiewicz, Jacek; Roliński, Jacek

    2013-01-01

    NKT cells are a heterogeneous subset of T lymphocytes that share surface markers and functional characteristics with both conventional T lymphocytes and natural killer cells. Most NKT cells express a semi-invariant T cell receptor that reacts with glycolipid antigens presented by the CD1d molecule on the surface of antigen-presenting cells. NKT cells can modulate the immune response against infectious agents, autoantigens, tumors, tissue grafts and allergens. NKT cells mediate the activities through their ability to express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. The manuscript summarizes current views on development of NKT cells as well as mechanisms and effects of their action.  PMID:23475484

  6. Development of psychophysiological motoric reactivity is influenced by peripubertal pharmacological inhibition of gonadotropin releasing hormone action--results of an ovine model.

    Evans, Neil P; Robinson, Jane E; Erhard, Hans W; Ropstad, Erik; Fleming, Lynne M; Haraldsen, Ira Ronit Hebold

    2012-11-01

    This study reports the effects of peripubertal GnRH receptor inactivation on development of psychophysiological motoric reactivity (PMR; sometimes also called emotional reactivity), plasma cortisol concentrations and the relationship between plasma cortisol and PMR in male and female sheep. The study formed part of a larger trial and utilised 46 same sex twins. One twin remained untreated (control) while the other received a subcutaneous GnRH agonist (GnRHa Goserelin-Acetate) implant every 4th week, beginning at 8 and 28 weeks of age, in males and females, respectively (different, due to sex specific age of puberty). PMR, a measure of an animals' response to social isolation, was measured over a two minute period at 8, 28 and 48 weeks of age, using a three axis accelerometer. During the test period vocalisation rate was recorded. Cortisol was assayed in blood samples collected on a single day when animals were 40 weeks of age. PMR and vocalisation rate were significantly higher in females than males at all ages tested. At 28 weeks of age (20 weeks treatment) PMR was increased in treated males to the level seen in control females, by 48 weeks of age treated males' PMR was significantly less than controls. In females, 20 weeks of GnRHa treatment (28-48 weeks of age) was not associated with differences in PMR. Cortisol concentrations were significantly higher in females than males but were not affected by treatment. Plasma cortisol concentrations were positively correlated with PMR; this relationship being driven by the treated animals in both sexes. The results demonstrate that PMR is sexually dimorphic and cortisol dependent in sheep from at least 8 weeks of age. Importantly, they also demonstrate that long-term treatment of males with a GnRH agonist results in changes in age-dependent development of PMR. PMID:22534405

  7. Mephedrone: Public health risk, mechanisms of action, and behavioral effects.

    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.' PMID:23764466

  8. Mapping the effects of three dopamine agonists with different dyskinetogenic potential and receptor selectivity using pharmacological functional magnetic resonance imaging.

    Delfino, Marina; Kalisch, Raffael; Czisch, Michael; Larramendy, Celia; Ricatti, Jimena; Taravini, Irene R E; Trenkwalder, Claudia; Murer, Mario Gustavo; Auer, Dorothee P; Gershanik, Oscar S

    2007-09-01

    The mechanisms underlying dopamine agonist-induced dyskinesia in Parkinson's disease remain poorly understood. Similar to patients, rats with severe nigrostriatal degeneration induced by 6-hydroxydopamine are more likely to show dyskinesia during chronic treatment with unselective dopamine receptor agonists than with D2 agonists, suggesting that D1 receptor stimulation alone or in conjunction with D2 receptor stimulation increases the chances of experiencing dyskinesia. As a first step towards disclosing drug-induced brain activation in dyskinesia, we examined the effects of dopamine agonists on behavior and blood oxygenation level-dependent (BOLD) signal in the striatum and motor cortex of rats with unilateral nigrostriatal lesions. Rats were rendered dyskinetic before pharmacologic functional magnetic resonance imaging by means of a repeated treatment regime with dopamine agonists. The unselective agonist apomorphine and the selective D1/D5 agonist SKF-81297 induced strong forelimb dyskinesia (FD) and axial dystonia and increased BOLD signal in the denervated striatum. Besides, SKF-81297 produced a significant but smaller BOLD increase in the intact striatum and a symmetric bilateral increase in the motor cortex. The D2 family agonist quinpirole, which induced mild dyskinesia on chronic treatment, did not produce BOLD changes in the striatum or motor cortex. Further evidence to support an association between BOLD changes and dyskinesia comes from a direct correlation between scores of FD and magnitude of drug-induced BOLD increases in the denervated striatum and motor cortex. Our results suggest that striatal and cortical activation induced by stimulation of D1/D5 receptors has a primary role in the induction of peak dose dyskinesia in parkinsonism. PMID:17287822

  9. Actions for adoption of effective dose equivalent standards

    Regulations related with radiological protection have been revised to adopt SI units and to accept the ICRP recommendation requesting to use the effective dose equivalent for radiation exposure control. The present report mainly deals with actions to be taken in the field of radiation instrumentation to promote the adoption of effective dose equivalent standards. In the past, exposure in roentgen has been generally used as a quantity to represent the intensity of a X-ray or alpha-ray field, because it can be measured relatively easily and accurately. The introduction of the effective dose equivalent is intended to establish annual exposure limits to ensure that the possibility of death of workers in a radioactive environment and that of development of hereditary disorders in their children or grandchildren will be maintained below permissible levels. The quantity is expressed as the sum of each organ's dose equivalent multiplied by a weight that reflects risks. Presently, such weights are assigned to seven organs including the gential glands and red marrow. Fixed-type area monitors and portable survey meters are used for work environment monitoring while film badges, TLDs, dosimeters, etc., are employed for personnel monitoring. (Nogami, K.)

  10. Self-action effects in semiconductor quantum dots

    Dneprovskii, V. S.; Kanev, A. R.; Kozlova, M. V.; Smirnov, A. M.

    2014-05-01

    Two-dimensional (2D) dynamic photonic crystal regime has been utilized to investigate self-diffraction effect and nonlinear optical properties of excitons in CdSe/ZnS colloidal quantum dots (QDs). Self-diffraction at 2D photonic crystal arises for three intersecting beams of Nd+3:YAG laser second harmonic in the case of one-photon resonant excitation of the exciton (electron - hole) transition QDs. The relaxation time of excited excitons has been measured by pump and probe technique at induced one-dimensional transient diffraction grating. Two-exponential decay with initial fast and slow parts was discovered. Self-action effect has been discovered in the case of stationary resonant excitation of excitons in CdSe/ZnS QDs by the beam of second harmonic of powerful 12-nanosecond laser pulses. The bleaching of exciton absorption and the creation of transparency channel (this effect provokes self-diffraction of the second harmonic beam) was explained by the dominating coexisting and competing processes of state filling in stationary excited quantum dots and Stark-shift of exciton spectral band. The peculiarities of the influence of these processes at the change of exciton absorption in quantum dots in the case of different detuning from exciton resonance (quantum dots with different size have been used) was analyzed.

  11. On the effects of action on visual perception & How new movement types are learned

    Beets, Iseult Anna Maria

    2010-01-01

    Perception can induce effects on action. Perception of others´ actions can thus influence our own actions. However, research on how action can shape perception is sparse. In this thesis, the effects of (i) motor learning and (ii) simple movements, can influence visual perception. Furthermore, the issue of motor learning is addressed; how can new movement types be learned and do active and passively guided motor training lead to ...

  12. The Geometry of Quantum Hall Effect: An Effective Action for all Dimensions

    Karabali, Dimitra; Nair, V. P.

    2016-01-01

    We present a general formula for the topological part of the effective action for quantum Hall systems in higher dimensions, including fluctuations of the gauge field and metric around background fields of a specified topological class. The result is based on a procedure of integrating up from the Dolbeault index density which applies for the degeneracies of Landau levels, combined with some input from the standard descent procedure for anomalies. Features of the topological action in (2+1), ...

  13. Ecological effects of contaminants and remedial actions in Bear Creek

    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.

  14. Scales, strategies and actions for effective energy planning: A review

    This paper is a review of the most recent literature on the interaction between climate change, land-use and energy, based on the analysis of papers collected through the most relevant scientific literature databases. A total of 114 papers published between 2000 and 2011 were reviewed. The aims of this review are: in general (1) to identify the different research topics that have been developed related to the interaction between climate change, land-use and energy; more specifically, (2) to analyze what are the most suitable spatial and temporal scales of investigation to focus on for actions and strategies to reduce critical issues in the field of energy and environment; (3) to identify which actions and strategies are deemed as the most appropriate to mitigate critical issues in energy and environment; and given the research gaps found in the review, (4) to propose research recommendations in the context of effective climate-energy planning. We argue that there are certain gaps and needs for a “nested” environmental governance. It is necessary to understand how different environmental policies overlap and how they can be integrated in order to verify whether there are conflicting targets that may negate each other in the long term. - Highlights: • Energy production and consumption can directly or indirectly affect climate change. • Energy sector is influenced directly and indirectly by changes in climate conditions. • Energy sector and climate change affect and limit alternative uses of land, causing land-use changes. • The most suitable spatial scale for energy planning is the municipal level requiring short-term perspectives. • Several research recommendations to deal with the complexity of energy-land-use-climate change issue are proposed

  15. Ecological effects of contaminants and remedial actions in Bear Creek

    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

  16. Formulary: Pharmacologic interventions in nuclear medicine

    The purpose of this formulary is to provide the practitioner with a readily available reference addressed specifically at the pharmacology (i.e., chemistry, mechanism(s) of action, cautions, dosage, and available preparation(s)) of interventional drugs commonly used in nuclear medicine practice. Although the majority of these agents are intended for alternate therapeutic indications, the formulary is directed at and limited to information pertinent to their interventional use. In this regard, the majority of the presented material has been extrapolated from standard drug formularies or product inserts. Specific material related to published interventional nuclear medicine studies is referenced in the bibliography and/or can be found in the associated chapters of this book. The reader is advised to note not only the information related to the interventional drug, but also the statements regarding appropriate treatment or avoidance of associated side effects. To facilitate utilization, the interventional drugs are listed in alphabetical order, rather than by therapeutic class

  17. Progress in pharmacological actions of ginsenoside compound K,an active metabolite of protopanaxadiol type saponins%原人参二醇型皂苷活性代谢物Compound K药理活性的研究进展

    李相鹏; 王鹏; 李英霞

    2011-01-01

    人参皂苷Compound K[CK,20-O-β-D-葡萄糖基-20(S)-原人参二醇]是原人参二醇型人参皂苷在人体内主要吸收形式和药效实体.近年来,CK的药理活性研究又有了新进展:① CK可通过活化胱天蛋白酶8直接或通过线粒体途径间接地激活胱天蛋白酶3,诱导肿瘤细胞凋亡;下调基质金属蛋白酶9基因的表达,抑制肿瘤细胞的转移;② 可通过下调多种炎症因子如白细胞介素-4(IL-4),IL-6,肿瘤坏死因子α等及环氧合酶2与一氧化氮合酶的表达而发挥抗炎、抗过敏和神经保护作用;③ 可阻断ATP敏感性K+离子通道,促进胰岛素分泌,增强组织胰岛素敏感性,抑制糖异生,促进糖酵解,对胰岛素依赖性糖尿病表现出良好的疗效;④ 可上调核苷切除修复相关蛋白基因的表达,减少紫外线引起的DNA损伤,防止皮肤老化等.本文重点对近几年有关CK的药理活性及其作用机制研究新进展进行综述.%Ginsenoside compound K ( CK ), 20-O-β- (D-glucopyranosyl) -20 ( S ) -protopanaxadiol, is a major form of protopanaxadiol type saponins absorbed by the human body after oral administration, and a real component that mediates pharmacologic actions. Recently, new progress has been made in studies on pharmacological actions:① CK can activate caspase 8, which plays a key role in CK-stimulated apoptosis via activation of caspase 3 directly or indirectly through mitochondria pathway and can regulate the metastasis and invasiveness of tumor cells by downregulating metalloproteinase 9 gene expression; ② CK can reduce expression levels of NO synthase and cyclooxygenase-2 and inhibit secretion of some pro-inflammatory cytokines like interleukin 4 ( IL4), IL-6 or tumor necrosis factor-α, which are responsible for its anti-inflammatory, anti-allergic, and neuro-protective activities; ③ CK can enhance the insulin secretion by blocking the ATP sensitive K + channel, improve insulin sensitivity, and shift glucose

  18. Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

    Morgan, Alexandra R., E-mail: alex.morgan@bioxydyn.com [Bioxydyn Ltd, Manchester (United Kingdom); Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Parker, Geoff J.M.; Roberts, Caleb [Bioxydyn Ltd, Manchester (United Kingdom); Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Buonaccorsi, Giovanni A.; Maguire, Niall C. [Bioxydyn Ltd, Manchester (United Kingdom); Hubbard Cristinacce, Penny L. [Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Singh, Dave; Vestbo, Jørgen [University of Manchester, Medicines Evaluation Unit, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester (United Kingdom); Bjermer, Leif [Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund (Sweden); Jögi, Jonas [Department of Clinical Physiology, Skåne University Hospital and Lund University, Lund (Sweden); Taib, Ziad; Sarv, Janeli; Bruijnzeel, Piet L.B.; Olsson, Lars E.; Bondesson, Eva [AstraZeneca R and D, Mölndal (Sweden); Nihlén, Ulf [Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund (Sweden); AstraZeneca R and D, Mölndal (Sweden); McGrath, Deirdre M. [Centre for Imaging Sciences and Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, University of Manchester, Manchester (United Kingdom); Young, Simon S. [AstraZeneca R and D, Alderley Park (United Kingdom); and others

    2014-11-15

    Highlights: • We investigate physiologic response to standard COPD treatment regimes using OE-MRI. • We assess the potential role of OE-MRI in future drug development studies. • In COPD, OE-MRI parameters showed response to single-dose formoterol. • OE-MRI parameters showed response to 8-week formoterol/budesonide treatment. • OE-MRI measurements are feasible in a small-scale multi-center trial setting. - Abstract: Objectives: Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methods: COPD patients (n = 40), mean FEV{sub 1} 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler{sup ®} 320/9 μg or formoterol Turbuhaler{sup ®}. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results: OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV{sub 1} was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies

  19. Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

    Highlights: • We investigate physiologic response to standard COPD treatment regimes using OE-MRI. • We assess the potential role of OE-MRI in future drug development studies. • In COPD, OE-MRI parameters showed response to single-dose formoterol. • OE-MRI parameters showed response to 8-week formoterol/budesonide treatment. • OE-MRI measurements are feasible in a small-scale multi-center trial setting. - Abstract: Objectives: Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methods: COPD patients (n = 40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9 μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results: OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV1 was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies. Conclusions: In COPD, OE

  20. Pharmacology Experiments on the Computer.

    Keller, Daniel

    1990-01-01

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

  1. Chinese Medicinal Leech: Ethnopharmacology, Phytochemistry, and Pharmacological Activities

    Dong, Han; Ren, Ji-Xiang; Wang, Jing-Jing; Ding, Li-Shuai; Zhao, Jian-Jun; Liu, Song-Yan; Gao, Hui-Min

    2016-01-01

    Hirudo (Shuizhi in Chinese) is an important Chinese medicine, which possesses many therapeutic properties for the treatment of the cerebral hemorrhage and other thrombosis-related diseases. The phytochemical investigation gave more than 51 compounds including pteridines, phosphatidylcholines, glycosphingolipids, and sterols, as well as some bioactive peptides from the Shuizhi derived from three animal species recorded in the current Chinese Pharmacopoeia. The pharmacological studies on the Shuizhi have revealed various activities such as anticoagulation, antithrombosis, antiatherosclerosis, antiplatelet aggregation, antitumor and anti-inflammatory as well as hemorheology improvement, and protective effects against cerebral ischemia-reperfusion injury. However, some important issues based on the traditional uses of Shuizhi are still not clear. The aim of the present review is to provide comprehensive knowledge on the ethnopharmacology, phytochemistry, and pharmacological activities of Shuizhi. It will provide a potential guidance in exploring main active compounds of Shuizhi and interpreting the action mechanism for the further research. PMID:27274755

  2. Chinese Medicinal Leech: Ethnopharmacology, Phytochemistry, and Pharmacological Activities

    Han Dong

    2016-01-01

    Full Text Available Hirudo (Shuizhi in Chinese is an important Chinese medicine, which possesses many therapeutic properties for the treatment of the cerebral hemorrhage and other thrombosis-related diseases. The phytochemical investigation gave more than 51 compounds including pteridines, phosphatidylcholines, glycosphingolipids, and sterols, as well as some bioactive peptides from the Shuizhi derived from three animal species recorded in the current Chinese Pharmacopoeia. The pharmacological studies on the Shuizhi have revealed various activities such as anticoagulation, antithrombosis, antiatherosclerosis, antiplatelet aggregation, antitumor and anti-inflammatory as well as hemorheology improvement, and protective effects against cerebral ischemia-reperfusion injury. However, some important issues based on the traditional uses of Shuizhi are still not clear. The aim of the present review is to provide comprehensive knowledge on the ethnopharmacology, phytochemistry, and pharmacological activities of Shuizhi. It will provide a potential guidance in exploring main active compounds of Shuizhi and interpreting the action mechanism for the further research.

  3. VNP: Interactive Visual Network Pharmacology of Diseases, Targets, and Drugs

    Hu, Q-N; Deng, Z.; Tu, W; X. Yang; Meng, Z-B; Deng, Z-X; Liu, J

    2014-01-01

    In drug discovery, promiscuous targets, multifactorial diseases, and “dirty” drugs construct complex network relationships. Network pharmacology description and analysis not only give a systems-level understanding of drug action and disease complexity but can also help to improve the efficiency of target selection and drug design. Visual network pharmacology (VNP) is developed to visualize network pharmacology of targets, diseases, and drugs with a graph network by using disease, target or dr...

  4. Effects and Mechanism of Action of a Tribulus terrestris Extract on Penile Erection

    Do, Jungmo; Choi, Seemin; Choi, Jaehwi; Hyun, Jae Seog

    2013-01-01

    Purpose Tribulus terrestris has been used as an aphrodisiac. However, little is known about the effects and mechanism of action of T. terrestris on penile erection. Therefore, the effect of a T. terrestris extract and the mechanism of action of the extract on relaxation of the corpus cavernosum (CC) were investigated. The erectogenic effects of an oral preparation of the extract were also assessed. Materials and Methods The relaxation effects and mechanism of action of the T. terrestris extra...

  5. Pharmacological evaluation of ameliorative effect of aqueous extract of Cucumis sativus L. fruit formulation on wound healing in Wistar rats

    Mithun Vishwanath K Patil

    2011-01-01

    Full Text Available Aim: The aim of present investigation was to formulate and evaluate the ameliorative effect of aqueous extract of Cucumis sativus L. fruit cream formulation on experimentally induced wounds in rats. Materials and Methods: The cream was formulated using soft white paraffin base containing 2.5%, 5%, and 10% w/w of aqueous extract of of Cucumis sativus L. fruit. Excision wounds of size 300 mm 2 and 2 mm depth were used for the study of rate of contraction of wound and epithelization. All the three formulations were evaluated for various pharmaceutical parameters such as pH, viscosity, spreadability, and acute skin irritation study. Epithelialization period, wound contraction, scar width, and histopathological evaluation parameters were used for pharmacological evaluation of wound healing activity of the formulation. Statistical Analysis: All the results were expressed as mean±SEM. Data analysis was performed using GraphPad Prism 5.0 software (GraphPad, San Diego, CA, USA. Statistical comparisons were made between drug-treated groups and disease control animals. Data of disease activity index were analyzed using one-way analysis of variance; Dunnett′s multiple range test was applied for post hoc analysis, whereas data of wound area and percent wound contraction were analyzed using two-way repeated analysis of variance, Bonferroni′s multiple range test was applied for post hoc analysis. A value of P<0.05 was considered to be statistically significant. Results: Cream formulation of AECS when applied topically did not show any sign and symptoms of skin irritation. The treatment with aqueous extract of C. sativus fruit cream formulation (2.5%, 5%, and 10% w/w resulted in significance decrease (P<0.05, P<0.001, and P<0.001, respectively in wound area, epithelization period, and scar width, whereas rate of wound contraction significance increased (P<0.001 respectively when compared with control group animals. Conclusion: The present investigation

  6. Pharmacology of antihypertensive drugs.

    Pepper, G A

    1999-01-01

    The wide variety of first-line agents available for managing high blood pressure include diuretics, beta adrenergic receptor blockers, alpha adrenergic receptor blockers, angiotensin converting enzyme inhibitors, and calcium channel blockers. Supplemental agents used for second-line therapy and special indications, such as pregnancy and hypertensive emergencies, include angiotensin receptor blockers, central-acting agents, direct vasodilators, and adrenergic neuron inhibitors. Selection of agents for particular patients requires consideration of research-based evidence for positive long-term outcomes and of the unique patient profile of age, race, co-morbidities, and lifestyle. A thorough understanding of the pharmacology (mechanism, pharmacokinetics, adverse effects and drug interactions, clinical use) of antihypertensive agents is an essential foundation for nursing practice in women's health. PMID:10584919

  7. Non-­‐pharmacological treatment of ankylosing spondylitis: Barriers to effective implementation of recommendations in Morocco

    Abderrazak Hajjioui

    2014-05-01

    Full Text Available This cross-sectional study aimed to describe non--‐pharmacological treatment modalities in Moroccan patients with ankylosing spondylitis (AS, and to approach physical therapy implementation barriers. 61 patients with AS according to New York classification criteria were included in the study. Socio-demographic data and clinical characteristics were collected and different therapeutic modalities, including physical therapy were investigated. The mean age of the patients was 38.20 (SD 12.36 years with a male/female ratio of 1.5. 55 (90% patients received pharmacological therapy, 37 (60.7% received physical therapy, 5(8.2% underwent surgery and 36 (59% tried at least one type of complementary medicine (medicine plants, sand baths, acupuncture, fire needles, and cupping. Patients’ major expectations from physical therapy were improving their functional status (86.5%, and reducing their pain (59.5%. Most patients (86.49% were satisfied of their physical therapy and 56.8% practiced home exercises. Reasons for nonattendance to physical therapy for the remaining 24 patients were nonprescription (58.3%, lack of financial resources (20.8%, geographical remoteness from rehabilitation centers (4% and lack of motivation (17%. Non-pharmacological treatment, especially based on exercise and education, is an integral part of the comprehensive management of AS. However, it is not efficiently implemented in Morocco and more effort should be made to develop this both efficient and relatively inexpensive component of AS treatment.

  8. Regulation of international energy markets: Economic effects of political actions

    Shcherbakova, Anastasia V.

    Recent increases in volatility of energy prices have led many governments to reevaluate their regard of national energy reserves and reconsider future exploration, production, and consumption patterns. The flurry of activity that has been generated by such price volatility has included large-scale nationalizations of energy sectors, unilateral renegotiations of foreign energy development contracts, and expropriations of resources from foreign energy firms on one hand, and on the other hand more rapid energy sector liberalization, intensified search for and development of renewable fuels and technologies, and development of incentives for increased energy efficiency and conservation. The aim of this dissertation is to examine and quantify the extent of positive and negative effects that have resulted from some of these activities. The first chapter focuses on quantifying the effect that nationalistic sentiment has had on economic attractiveness of energy sectors during the decade prior to the recent global economic crisis, as measured by foreign direct investment (FDI) inflows. Empirical results demonstrate that both political and economic conditions play an important role in investors' decisions. A combination of investment friendliness, corruption levels, and democracy all help to explain the trends in energy-sector investment levels over time in my sample countries, although differences in the types of corruption existing in these nations do not. Investment levels, in turn, appear to influence future levels of oil production, underscoring the significance of good investment policies for future success of energy sectors. Chapter two considers the response of energy stock prices to severe regulatory actions. It employs an event study framework to examine causal effects of critical informational announcements (i.e. events of expropriation and nationalization) on daily returns and cumulative losses in firm value of energy corporations. Results show that a firm

  9. Effects of action video game training on visual working memory.

    Blacker, Kara J; Curby, Kim M; Klobusicky, Elizabeth; Chein, Jason M

    2014-10-01

    The ability to hold visual information in mind over a brief delay is critical for acquiring information and navigating a complex visual world. Despite the ubiquitous nature of visual working memory (VWM) in our everyday lives, this system is fundamentally limited in capacity. Therefore, the potential to improve VWM through training is a growing area of research. An emerging body of literature suggests that extensive experience playing action video games yields a myriad of perceptual and attentional benefits. Several lines of converging work suggest that action video game play may influence VWM as well. The current study utilized a training paradigm to examine whether action video games cause improvements to the quantity and/or the quality of information stored in VWM. The results suggest that VWM capacity, as measured by a change detection task, is increased after action video game training, as compared with training on a control game, and that some improvement to VWM precision occurs with action game training as well. However, these findings do not appear to extend to a complex span measure of VWM, which is often thought to tap into higher-order executive skills. The VWM improvements seen in individuals trained on an action video game cannot be accounted for by differences in motivation or engagement, differential expectations, or baseline differences in demographics as compared with the control group used. In sum, action video game training represents a potentially unique and engaging platform by which this severely capacity-limited VWM system might be enhanced. PMID:25068696

  10. Effect of Composite Action on the Strength of Wood Roofs

    Ivan A. Campos Varela

    2015-01-01

    Full Text Available Engineering certification for the installation of solar photovoltaic modules on wood roofs is often denied because existing wood roofs do not meet current building codes. Rather than requiring expensive structural retrofits, we desire to show that many roofs are actually sufficiently strong if the effect of composite action produced by joist-sheathing interaction is considered. In a series of laboratory experiments using a limited number of two-by-four wood joists with and without sheathing panels, conventionally sheathed stud-grade joists, surprisingly, exhibited between 18% and 63% higher nominal strength than similar bare joists. To explain this strength increase, a simple model was developed to predict the strengths of the nailed partially composite sections, but the model only justifies a 1.4% to 3.8% increase in bending strength of joists with an allowable bending strength of 1000 psi. More testing is indicated to resolve this discrepancy between laboratory results and analytical modeling results. In addition to elucidating nonlinear partial composite behavior of existing roof systems, this paper shows that, with minor changes in roof framing practices, strength increases of 70% or more are achievable, compared to the strengths of conventionally sheathed joists.

  11. Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects.

    Brglez Mojzer, Eva; Knez Hrnčič, Maša; Škerget, Mojca; Knez, Željko; Bren, Urban

    2016-01-01

    Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco-friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity. PMID:27409600

  12. The pharmacological features of bilirubin: the question of the century.

    Zahir, Farhana; Rabbani, Gulam; Khan, Rizwan Hasan; Rizvi, Shamim J; Jamal, Mohammad Sarwar; Abuzenadah, Adel M

    2015-09-01

    This review looks at the toxicity and metabolism of bilirubin in terms of its pharmacological potential. Its role has gained importance as more research has revealed the functional significance and interrelationship between the gasotransmitters nitric oxide and carbon monoxide. The biological actions of bilirubin have mostly been characterized in the high micromolar range where toxic effects occur. However, it could also prove to be an important cytoprotector for brain tissue, which is inherently less equipped for antioxidant defense. Plasma bilirubin levels negatively correlate to a number of disease states. Higher levels of bilirubin that are still within the normal range provide a protective effect to the body. The effects on various disorders could be tested using controlled pharmacological upregulation of the molecule with animal models. At nanomolar concentrations, considerable benefits have been obtained when the molecule was delivered pharmacologically under in vitro or in vivo test conditions, particularly in neurodegenerative disorders and after tissue or organ transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of nuclear factor erythroid 2-related factor or the use of bile pigments in the harvesting of diseased tissue are novel applications, and like every new therapy, should be used with caution. HMOX-1 is tissue specific, and in exceptional states, such as schizophrenia and specific types of renal disorder, the same therapy may have disastrous effects. PMID:26208389

  13. Marine pharmacology in 2003-4: Marine Compounds with Anthelminthic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    Mayer, Alejandro M. S.; Rodriguez, Abimael D.; Berlinck, Roberto G. S.; Hamann, Mark T.

    2007-01-01

    The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998-2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine com...

  14. On compatibility of string effective action with an accelerating universe

    Neupane, Ishwaree P [Department of Physics and Astronomy, University of Canterbury, Private Bag 4800, Christchurch (New Zealand); Central Department of Physics, Tribhuvan University, Kirtipur, Kathmandu (Nepal)

    2006-12-21

    In this paper, we fully investigate the cosmological effects of the moduli-dependent one-loop corrections to the gravitational couplings of the string effective action to explain the cosmic acceleration problem in the early (and/or late) universe. These corrections comprise a Gauss-Bonnet (GB) invariant multiplied by universal non-trivial functions of the common modulus {sigma} and the dilaton {phi}. The model exhibits several features of cosmological interest, including the transition between deceleration and acceleration phases. By considering some phenomenologically motivated ansatze for one of the scalars and/or the scale factor (of the universe), we also construct a number of interesting inflationary potentials. In all examples under consideration, we find that the model leads only to a standard inflation (w {>=} -1) when the numerical coefficient {delta} associated with modulus-GB coupling is positive, while the model can also lead to a non-standard inflation (w < -1), if {delta} is negative. In the absence of (or trivial) coupling between the GB term and the scalars, there is no crossing between the w < -1 and w > -1 phases, while this is possible with non-trivial GB couplings, even for the constant dilaton phase of the standard picture. Within our model, after a sufficient amount of e-folds of expansion, the rolling of both fields {phi} and {sigma} can be small. In turn, any possible violation of equivalence principle or deviations from the standard general relativity may be small enough to easily satisfy all astrophysical and cosmological constraints.

  15. Renormalization-group flow of the effective action of cosmological large-scale structures

    Floerchinger, Stefan; Garny, Mathias; Tetradis, Nikolaos; Wiedemann, Urs Achim

    2016-01-01

    Following an approach of Matarrese and Pietroni, we derive the functional renormalization group (RG) flow of the effective action of cosmological large-scale structures. Perturbative solutions of this RG flow equation are shown to be consistent with standard cosmological perturbation theory. Non-perturbative approximate solutions can be obtained by truncating the a priori infinite set of possible effective actions to a finite subspace. Using for the truncated effective action a form dictated ...

  16. Experts see it all: configural effects in action observation

    Calvo-Merino, B.; Ehrenberg, S; Leung, D. M. H.; Haggard, P

    2010-01-01

    Biological motion perception is influenced by observers’ familiarity with the observed action. Here we used classical dance as a means to investigate how visual and motor experience modulates perceptual mechanism for configural processing of actions. While some ballet moves are performed by only one gender, male and female dancers train together and acquire visual knowledge of all ballet moves. 24 expert ballet dancers (12 female) and matched non-expert participants viewed pairs of upright an...

  17. The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in Huntington’s Disease Mice

    Jia, Haiqun; Wang, Ying; Morris, Charles D.; Jacques, Vincent; Gottesfeld, Joel M.; Rusche, James R.; Thomas, Elizabeth A.

    2016-01-01

    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-yl)acrylamide), 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. PMID:27031333

  18. Antioxidant effects of carotenoids

    Bast, A.; Haenen, G.R.M.M.; Berg, R. van den; Berg, H. van den

    1998-01-01

    Surprisingly, neither the precise pharmacological effect nor the toxicological profile is usually established for food components. Carotenoids are no exception in this regard. Only limited insight into the pharmacology and toxicology of carotenoids exists. It is known that the antioxidant action of

  19. Phyto-pharmacology of Celastrus paniculatus: An Overview

    M. Bhanumathy

    2010-07-01

    Full Text Available Celastrus paniculatus (CP, a traditional Ayurvedic medicinal plant used for centuries as a memory enhancing, anti-inflammatory, analgesic, sedative and antiepileptic agent. The seed extract has been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, anticonvulsant and other pharmacological effects of CP preparations/extracts. Therefore, in view of the important activities performed by this plant, investigation must be continued in the recently observed actions described in this paper. Moreover, clinical studies have to be encouraged, also to evidence any side effects and possible interactions between this herbal medicine and synthetic drugs.

  20. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

    Thomas Hart; Shihab Dider; Weiwei Han; Hua Xu; Zhongming Zhao; Lei Xie

    2016-01-01

    Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification ...

  1. The effects of an action video game on visual and affective information processing.

    Bailey, Kira; West, Robert

    2013-04-01

    Playing action video games can have beneficial effects on visuospatial cognition and negative effects on social information processing. However, these two effects have not been demonstrated in the same individuals in a single study. The current study used event-related brain potentials (ERPs) to examine the effects of playing an action or non-action video game on the processing of emotion in facial expression. The data revealed that 10h of playing an action or non-action video game had differential effects on the ERPs relative to a no-contact control group. Playing an action game resulted in two effects: one that reflected an increase in the amplitude of the ERPs following training over the right frontal and posterior regions that was similar for angry, happy, and neutral faces; and one that reflected a reduction in the allocation of attention to happy faces. In contrast, playing a non-action game resulted in changes in slow wave activity over the central-parietal and frontal regions that were greater for targets (i.e., angry and happy faces) than for non-targets (i.e., neutral faces). These data demonstrate that the contrasting effects of action video games on visuospatial and emotion processing occur in the same individuals following the same level of gaming experience. This observation leads to the suggestion that caution should be exercised when using action video games to modify visual processing, as this experience could also have unintended effects on emotion processing. PMID:23419898

  2. Morphology, pharmacological activity, pharmaceutical preparation, doses and side effect of Coccinia indica (Wight & Arn.):An overview

    Mayank Kumar; Shashi Alok; Sanjay Kumar Jain; Amita Verma; Alok Mahor; Monika Sabharwal

    2013-01-01

    Traditional system of medicine consists of large number of plants with various medicinal and pharmacological importances and hence represents a priceless tank of new bioactive molecules.Coccinia indica belongs to the family Cucurbitaceae. It is a rapidly growing, perennial climber or trailing vine. Traditionally different parts of this plant namely the roots, leaves and fruits are used in folklore medicine for several purposes like jaundice, diabetes, wound healing, ulcers, stomach ache, skin disease, fever, asthma, cough. The leaf and its constituents have been reported to possess hypoglycaemic, hypolipidemic and antioxidant properties. This review provides adequate information to develop suitable therapeutics out of these plant parts.

  3. Conception of Pharmacological Knowledge and Needs Amongst Nigerian Medical Students at Lagos State University College of Medicine: Implication for Future Biomedical Science in Africa.

    Agaga, Luther Agbonyegbeni; John, Theresa Adebola

    2016-01-01

    In Nigeria, medical students are trained in more didactic environments than their counterparts in researchintensive academic medical centers. Their conception of pharmacology was thus sought. Students who are taking/have takenthe medical pharmacology course completed an 18-question survey within 10min by marking one/more choices fromalternatives. Instructions were: "Dear Participant, Please treat as confidential, give your true view, avoid influences, avoidcrosstalk, return survey promptly." Out of 301 students, 188 (62.46%) participated. Simple statistics showed: 61.3%respondents associated pharmacology with medicine, 24.9% with science, 16.8 % with industry, and 11.1% with government;32.8% want to know clinical pharmacology, 7.1% basic pharmacology, 6.7% pharmacotherapy, and 34.2% want a blend ofall three; 57.8% want to know clinical uses of drugs, 44.8% mechanisms of action, 44.4% side effects, and 31.1% differentdrugs in a group; 45.8% prefer to study lecturers' notes, 26.7% textbooks, 9.8% the Internet, and 2.7% journals; 46.7% usestandard textbooks, 11.5% revision texts, 2.66% advanced texts, and 8.4% no textbook; 40.4% study pharmacology to beable to treat patients, 39.1% to complete the requirements for MBBS degree, 8.9% to know this interesting subject, and 3.1%to make money. Respondents preferring aspects of pharmacology were: 42.7, 16, 16, and 10 (%) respectively for mechanismsof action, pharmacokinetics, side effects, and drug lists. Medical students' conception and need for pharmacology werebased on MBBS degree requirements; they lacked knowledge/interest in pharmacology as a science and may not be thepotential trusts for Africa's future pharmacology. PMID:27574769

  4. Methodological innovations expand the safety pharmacology horizon.

    Pugsley, M K; Curtis, M J

    2012-09-01

    Almost uniquely in pharmacology, drug safety assessment is driven by the need for elaboration and validation of methods for detecting drug actions. This is the 9th consecutive year that the Journal of Pharmacological and Toxicological Methods (JPTM) has published themed issues arising from the annual meeting of the Safety Pharmacology Society (SPS). The SPS is now past its 10th year as a distinct (from pharmacology to toxicology) discipline that integrates safety pharmacologists from industry with those in academia and the various global regulatory authorities. The themes of the 2011 meeting were (i) the bridging of safety assessment of a new chemical entity (NCE) between all the parties involved, (ii) applied technologies and (iii) translation. This issue of JPTM reflects these themes. The content is informed by the regulatory guidance documents (S7A and S7B) that apply prior to first in human (FIH) studies, which emphasize the importance of seeking model validation. The manuscripts encompass a broad spectrum of safety pharmacology topics including application of state-of-the-art techniques for study conduct and data processing and evaluation. This includes some exciting novel integrated core battery study designs, refinements in hemodynamic assessment, arrhythmia analysis algorithms, and additionally an overview of safety immunopharmacology, and a brief survey discussing similarities and differences in business models that pharmaceutical companies employ in safety pharmacology, together with SPS recommendations on 'best practice' for the conduct of a non-clinical cardiovascular assessment of a NCE. PMID:22617368

  5. The Geometry of Quantum Hall Effect: An Effective Action for all Dimensions

    Karabali, Dimitra

    2016-01-01

    We present a general formula for the topological part of the effective action for quantum Hall systems in higher dimensions, including fluctuations of the gauge field and metric around background fields of a specified topological class. The result is based on a procedure of integrating up from the Dolbeault index density which applies for the degeneracies of Landau levels, combined with some input from the standard descent procedure for anomalies. Features of the topological action in (2+1), (4+1), (6+1) dimensions, including the contribution due to gravitational anomalies, are discussed in some detail.

  6. Geometry of the quantum Hall effect: An effective action for all dimensions

    Karabali, Dimitra; Nair, V. P.

    2016-07-01

    We present a general formula for the topological part of the effective action for integer quantum Hall systems in higher dimensions, including fluctuations of the gauge field and metric around background fields of a specified topological class. The result is based on a procedure of integrating up from the Dolbeault index density which applies for the degeneracies of Landau levels, combined with some input from the standard descent procedure for anomalies. Features of the topological action in (2 +1 ), (4 +1 ), (6 +1 ) dimensions, including the contribution due to gravitational anomalies, are discussed in some detail.

  7. Effective actions for F-theory compactifications and tensor theories

    In this thesis we study the low-energy effective dynamics emerging from a class of F-theory compactifications in four and six dimensions. We also investigate six-dimensional supersymmetric quantum field theories with self-dual tensors, motivated by the problem of describing the long-wavelength regime of a stack of M5-branes in M-theory. These setups share interesting common features. They both constitute examples of intrinsically non-perturbative physics. On the one hand, in the context of F-theory the non-perturbative character is encoded in the geometric formulation of this class of string vacua, which allows the complexified string coupling to vary in space. On the other hand, the dynamics of a stack of multiple M5-branes flows in the infrared to a novel kind of superconformal field theories in six dimensions - commonly referred to as (2,0) theories - that are expected to possess no perturbative weakly coupled regime and have resisted a complete understanding so far. In particular, no Lagrangian description is known for these models. The strategy we employ to address these two problems is also analogous. A recurring Leitmotif of our work is a transdimensional treatment of the system under examination: in order to extract information about dynamics in d dimensions we consider a (d-1)-dimensional setup. As far as F-theory compactifications are concerned, this is a consequence of the duality between M-theory and F-theory, which constitutes our main tool in the derivation of the effective action of F-theory compactifications. We apply it to six-dimensional F-theory vacua, obtained by taking the internal space to be an elliptically fibered Calabi-Yau threefold, but we also employ it to explore a novel kind of F-theory constructions in four dimensions based on manifolds with Spin(7) holonomy. With reference to six-dimensional (2,0) theories, the transdimensional character of our approach relies in the idea of studying these theories in five dimensions. Indeed, we

  8. The accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with adenosine triphosphate disodium (ATP) infusion in the diagnosis of coronary artery disease

    The diagnostic accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with ATP infusion were studied in 172 patients with or without coronary artery disease. ATP was infused for five minutes at a rate of 0.16 mg/kg/min (group A) or 0.18 mg/kg/min (group B) via antecubital vein. One hundred and eleven (67 of group A, 44 of group B) of 172 patients underwent coronary arteriography (CAG). In 111 patients received CAG, overall sensitivity, specificity and accuracy of this method were 88%, 84% and 87%, respectively. In 67 patients of group A, these were 92%, 81% and 90%. In 44 patients of group B, 79%, 87% and 82% were documented (NS, between groups A and B). Chest pain, flushing, bradycardia and ST depression were included in side effects caused by ATP infusion. At least one of these side effects were observed in 84% of the all 172 patients, 89% of group A and 75% of group B (NS). But, all of the side effects were spontaneously alleviated within two minutes without any therapy. In conclusion, pharmacologic stress myocardial scintigraphy with ATP infusion is very accurate and safe, and infusion rate of 0.16 mg/kg/min is optimal for this purpose. (author)

  9. Interactions between sentence comprehension and concurrent action: The role of movement effects and timing

    Diefenbach, C

    2010-01-01

    Embodied approaches to language comprehension suggest that we understand sentences by using our perception and action systems for simulating their contents. In line with this assumption, the action-sentence compatibility effect (ACE) shows that sensibility judgments for sentences are faster when the direction of the described action matches the direction of the response movement. The aim of this thesis was to investigate whether this compatibility is effective between sentence direction and m...

  10. Paradoxical pharmacology: turning our pharmacological models upside down.

    Page, Clive

    2011-04-01

    Paradoxical pharmacology is a term first suggested by Richard Bond to refer to intriguing observations that chronic use of some drug types can have the opposite biological effect(s) to those seen following acute administration of the same drug. A good example of 'paradoxical pharmacology' is the research Richard has pioneered showing that whereas acute administration of β-blockers is contraindicated in the treatment of asthma, chronic use of certain β-blockers can have therapeutic benefit. It would appear that those β-blockers that can act as inverse agonists at the β2 receptor particularly show this paradoxical effect and the findings of Richard's research not only challenge the dogma of the treatment of asthma but also challenge many of the pharmacological principles of ligand/receptor interactions established by Sir James Black and others. In this paper, I discuss Richard's efforts to evaluate the chronic effects of β-blockers in the airways and how this research caught the imagination of Sir James Black. PMID:21458081

  11. Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B-cell acute lymphoblastic leukaemia.

    Randhawa, Shubhchintan; Cho, Byung S; Ghosh, Dipanjan; Sivina, Mariela; Koehrer, Stefan; Müschen, Markus; Peled, Amnon; Davis, Richard E; Konopleva, Marina; Burger, Jan A

    2016-08-01

    B cell acute lymphoblastic leukaemia (B-ALL) cells express high levels of CXCR4 chemokine receptors for homing and retention within the marrow microenvironment. Bone marrow stromal cells (BMSC) secrete CXCL12, the ligand for CXCR4, and protect B-ALL cells from cytotoxic drugs. Therefore, the therapeutic use of CXCR4 antagonists has been proposed to disrupt cross talk between B-ALL cells and the protective stroma. Because CXCR4 antagonists can have activating agonistic function, we compared the genetic and pharmacological deletion of CXCR4 in B-ALL cells, using CRISPR-Cas9 gene editing and CXCR4 antagonists that are in clinical use (plerixafor, BKT140). Both genetic and pharmacological CXCR4 inhibition significantly reduced B-ALL cell migration to CXCL12 gradients and beneath BMSC, and restored drug sensitivity to dexamethasone, vincristine and cyclophosphamide. NOD/SCID/IL-2rγnull mice injected with CXCR4 gene-deleted B-ALL cells had significant delay in disease progression and superior survival when compared to control mice injected with CXCR4 wild-type B-ALL cells. These findings indicate that anti-leukaemia activity of CXCR4 antagonists is primarily due to CXCR4 inhibition, rather than agonistic activity, and corroborate that CXCR4 is an important target to overcome stroma-mediated drug resistance in B-ALL. PMID:27071778

  12. [Pharmacological treatment of obesity].

    Gomis Barbará, R

    2004-01-01

    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite. PMID:15382615

  13. Effects of context on visuomotor interference depends on the perspective of observed actions.

    Marta Bortoletto

    Full Text Available Visuomotor interference occurs when the execution of an action is facilitated by the concurrent observation of the same action and hindered by the concurrent observation of a different action. There is evidence that visuomotor interference can be modulated top-down by higher cognitive functions, depending on whether own performed actions or observed actions are selectively attended. Here, we studied whether these effects of cognitive context on visuomotor interference are also dependent on the point-of-view of the observed action. We employed a delayed go/no-go task known to induce visuomotor interference. Static images of hand gestures in either egocentric or allocentric perspective were presented as "go" stimuli after participants were pre-cued to prepare either a matching (congruent or non-matching (incongruent action. Participants performed this task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context, whereas in the other they focused on the hand gesture they performed (action context. We analyzed reaction times to initiate the prepared action upon presentation of the gesture image and found evidence of visuomotor interference in both contexts and for both perspectives. Strikingly, results show that the effect of cognitive context on visuomotor interference also depends on the perspective of observed actions. When focusing on own-actions, visuomotor interference was significantly less for gesture images in allocentric perspective than in egocentric perspective; when focusing on observed actions, visuomotor interference was present regardless of the perspective of the gesture image. Overall these data suggest that visuomotor interference may be modulated by higher cognitive processes, so that when we are specifically attending to our own actions, images depicting others' actions (allocentric perspective have much less interference on our own actions.

  14. Clinical pharmacology and vascular risk.

    Silvestrelli, G; Corea, F; Micheli, S; Lanari, A

    2010-01-01

    Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence. Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk. These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency. In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management. The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease. This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real

  15. Comment on ``Functional integral for Weyl fermions and the effective action''

    Banerjee, R.; Banerjee, H.

    1989-02-01

    Baaklini's method of obtaining the effective action for Weyl fermions is shown to yield either a gauge-invariant or a gauge-variant form depending on the specific definition employed in the analysis. The structures of the effective action proposed by Baaklini are found to correspond to the standard expressions.

  16. Conformally covariant operators and the effective action in an external gravitational field

    The n-dimensional expressions for the second-order conformally covariant differential operators acting on vector and tensor fields and for the fourth-order conformally covariant operator acting on scalar fields are obtained. For the fourth-order operator one-loop effective action is evaluated in four dimensions. The possibility of effective action evaluation for other conformally covariant operators is discussed

  17. Pharmacologic Therapies in Musculoskeletal Conditions.

    Loveless, Melinda S; Fry, Adrielle L

    2016-07-01

    Musculoskeletal conditions are common, and there are many options for pharmacologic therapy. Unfortunately, there is not strong evidence for the use of many of these medications. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are generally first-line medications for most musculoskeletal pain, but there is more evidence these medications are not as safe as once thought. Other analgesic and antispasmodic medications can be effective for acute pain but generally are not as effective for chronic pain. Antidepressants and anticonvulsants can be more effective for chronic or neuropathic pain. Topical formulations of NSAIDs can be effective for pain with fewer side effects. PMID:27235619

  18. Who needs pharmacologic therapy?

    Christopher Porterfield; Rohit Malhotra

    2014-06-01

    Full Text Available Treatment of atrial fibrillation has evolved significantly in the last ten years, with ablation becoming a far more common form of treatment for this most common of arrhythmias. However, while ablation has become more common, certain populations derive continued benefit from the use of pharmacologic therapy for treatment. We review the use of pharmacologic therapy and novel considerations for treatment of atrial fibrillation.

  19. 77 FR 1696 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    2012-01-11

    ... 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... pharmacology aspects of pediatric clinical trial design and dosing to optimize pediatric drug development....

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

    2010-02-24

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

  1. Pharmacologic interventions in aging hair

    Trüeb, Ralph M

    2006-01-01

    The appearance of hair plays an important role in people’s overall physical appearance and self-perception. With today’s increasing life-expectations, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and is delivering active products directed towards meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of heal...

  2. Pharmacologic management of eating disorders.

    Price, W A

    1988-05-01

    Treatment of eating disorders is difficult regardless of the methods employed. Pharmacologic management in anorexia nervosa and in bulimia nervosa is especially helpful when it is part of a multimodal treatment approach that includes individual, family and behavioral therapy. Care must be taken to guard against side effects, abuse and noncompliance in a group of patients that tends to be prone to all three. PMID:3284300

  3. Research progress of Tribulus terrestris composition and main pharmaco-logic effects%蒺藜成分及主要药理作用研究进展

    候爽; 陈长军; 杨博; 于飞飞; 崔晓莉; 孟雨; 田洪艳; 李质馨

    2014-01-01

    中药蒺藜中含有多种重要的生物活性物质如皂苷类、黄酮类等的化合物,具有众多的药理作用。现代医学研究证明,蒺藜具有显著的抗衰老、降血糖、降血脂、性强壮及提高人体中性激素含量等的作用,对肿瘤、高血压、细菌真菌感染、糖尿病等均有较好疗效。本文主要对近年来中药蒺藜成分及主要药理作用研究进展进行综述。%Traditional Chinese medicine (TCM) Tribulus terrestris contains a variety of important biological active substances, such as saponins, flavonoids and other compounds, which has many pharmacological effects. Modern medi-cal research indicates that Tribulus terrestris can remarkably delay senescence, reduce blood glucose and blood lipid, strengthen sexual function and enhance the sex hormones in the human body, etc. And it has good curative effects for cancer, high blood pressure, bacteria and fungal infections, diabetes and etc. This article mainly discusses the research progress on Tribulus terrestris composition and its main pharmacological activities in recent years.

  4. 2013 Pharmacology Risk SRP Status Review Comments to Chief Scientist. The Risk of Clinically Relevant Unpredicted Effects of Medication

    2014-01-01

    On December 5, 2013, the Pharmacology Risk SRP, participants from the JSC, HQ, the NSBRI, and NRESS participated in a WebEx/teleconference. The purpose of the call (as stated in the Statement of Task) was to allow the SRP members to: 1. Receive an update by the HRP Chief Scientist or Deputy Chief Scientist on the status of NASA's current and future exploration plans and the impact these will have on the HRP. 2. Receive an update on any changes within the HRP since the 2012 SRP meeting. 3. Receive an update by the Element or Project Scientist(s) on progress since the 2012 SRP meeting. 4. Participate in a discussion with the HRP Chief Scientist, Deputy Chief Scientist, and the Element regarding possible topics to be addressed at the next SRP meeting.

  5. The Effect of Timing on Gliclazide Absorption and Action

    Ishibashi, Fukashi; Takashina, Seiryo

    1990-01-01

    In this study we tried to determine when in relation to meals gliclazide should be taken for optimum hypoglycemic action. Eight non-insulin-dependent diabetics participated in this study during hospitalization for glycemic control.   After stabilization of glycemic control on gliclazide, they took a 40 mg tablet of gliclazide either 30 minutes before, immediately before, or immediately after breakfast on 3 consecutive days. We then determined serum gliclazide, glucose and IRI levels at 30...

  6. On the effective character of a non abelian DBI action

    Osorio, M A R; Suárez, María

    2001-01-01

    We study the way Lorentz covariance can be reconstructed from Matrix Theory as a IMF description of M-theory. The problem is actually related to the interplay between a non abelian Dirac-Born-Infeld action and Super-Yang-Mills as its generalized non-relativistic approximation. All this physics shows up by means of an analysis of the asymptotic expansion of the Bessel functions $K_\

  7. Studies on pharmacological effects of Russell's viper and Saw-scaled viper venom and its neutralization by chicken egg yolk antibodies.

    Meenatchisundaram, S; Parameswari, G; Michael, A; Ramalingam, S

    2008-08-01

    Antivenom antibodies were raised in 24-week-old white leghorn chickens against hemotoxic venoms of Russell's viper and Saw-scaled viper snakes. Booster injections of increasing concentrations of venom were given at 14days of time interval to raise the antivenom level in egg yolk. Antibodies were extracted from immunized chicken egg yolk by Polson et al. (Polson A., Von Wechmar M.B., Van Regenmortel M.H.V. Isolation of viral IgY antibodies from yolks of immunized hens. Immunological Communications 1980; 9:475-493.) and further purified by DEAE cellulose ion exchange column chromatography, which gave pure (180-200kDa) specific antibodies against venom. High titre of more than 1:10,000 antibodies were detected by ELISA at the 135th day of observation. The lethal toxicity and various pharmacological activities like hemorrhagic activity, phospholipase activity, edema and procoagulant activities of venom were carried out by both in vivo and in vitro methods. The effectiveness of antivenom in neutralizing these effects was carried out involving pre-incubation type experiments. The median effective dose (ED50) for Russell's viper venom was 0.96mg/2LD50/18g mice and for Saw-scaled viper venom it was 1.28mg/2LD50/18g mice. One millilitre of specific antivenom was effective in neutralizing 0.110mg of Russell's viper and 0.137mg of Saw-scaled viper venoms respectively (PD50). Antivenom was effective in neutralization assays in a dose dependent manner. The results indicate that antibodies raised in chicken could effectively neutralize the pharmacological effects induced by venoms and chickens therefore present an alternative and cheaper source of specific antibody generation. PMID:18550009

  8. The Side-Effect Effect in Children Is Robust and Not Specific to the Moral Status of Action Effects

    Rakoczy, Hannes; Behne, Tanya; Clüver, Annette; Dallmann, Stephanie; Weidner, Sarah; Waldmann, Michael R.

    2015-01-01

    Adults’ intentionality judgments regarding an action are influenced by their moral evaluation of this action. This is clearly indicated in the so-called side-effect effect: when told about an action (e.g. implementing a business plan) with an intended primary effect (e.g. raise profits) and a foreseen side effect (e.g. harming/helping the environment), subjects tend to interpret the bringing about of the side effect more often as intentional when it is negative (harming the environment) than when it is positive (helping the environment). From a cognitive point of view, it is unclear whether the side-effect effect is driven by the moral status of the side effects specifically, or rather more generally by its normative status. And from a developmental point of view, little is known about the ontogenetic origins of the effect. The present study therefore explored the cognitive foundations and the ontogenetic origins of the side-effect effect by testing 4-to 5-year-old children with scenarios in which a side effect was in accordance with/violated a norm. Crucially, the status of the norm was varied to be conventional or moral. Children rated the bringing about of side-effects as more intentional when it broke a norm than when it accorded with a norm irrespective of the type of norm. The side-effect effect is thus an early-developing, more general and pervasive phenomenon, not restricted to morally relevant side effects. PMID:26218422

  9. Pharmacological Overview of Galactogogues

    Felipe Penagos Tabares

    2014-01-01

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

  10. Pharmacological potential of cerium oxidenanoparticles

    Celardo, Ivana; Pedersen, Jens Z.; Traversa, Enrico; Ghibelli, Lina

    2011-04-01

    Nanotechnology promises a revolution in pharmacology to improve or create ex novo therapies. Cerium oxidenanoparticles (nanoceria), well-known as catalysts, possess an astonishing pharmacological potential due to their antioxidant properties, deriving from a fraction of Ce3+ ions present in CeO2. These defects, compensated by oxygen vacancies, are enriched at the surface and therefore in nanosized particles. Reactions involving redox cycles between the Ce3+ and Ce4+oxidation states allow nanoceria to react catalytically with superoxide and hydrogen peroxide, mimicking the behavior of two key antioxidant enzymes, superoxide dismutase and catalase, potentially abating all noxious intracellularreactive oxygen species (ROS) via a self-regenerating mechanism. Hence nanoceria, apparently well tolerated by the organism, might fight chronic inflammation and the pathologies associated with oxidative stress, which include cancer and neurodegeneration. Here we review the biological effects of nanoceria as they emerge from in vitro and in vivo studies, considering biocompatibility and the peculiar antioxidant mechanisms.

  11. [Effect of a non-pharmacological intervention, Voix d'Or(®), on behavior disturbances in Alzheimer disease and associated disorders].

    Delphin-Combe, Floriane; Rouch, Isabelle; Martin-Gaujard, Géraldine; Relland, Solveig; Krolak-Salmon, Pierre

    2013-09-01

    An innovative non-pharmacological intervention called Voix d'Or(®) (Golden Voice) was proposed in the Cognitive behavioral unit (CBU) of the Memory center at the Hospices civils in Lyon. Voix d'Or(®) offers eight sound activities disseminated via an audio device based on different approaches sociotherapeutic (music therapy, reminiscence, relaxation, reorientation in reality). The aim of this study was to test the effects of the Voix d'Or(®) program on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease hospitalized in the CBU. Twenty four patients with agitation and/or apathy and/or anxiety and/or depression were included. Patients were randomly selected in the intervention group exposed to Voix d'Or versus a control group exposed to usual occupational activities. Patients were assessed before (T0) and after (T1) the intervention period. Several variables were measured: frequency and severity of behavioral disorders, anxiety, depression, agitation and apathy. A significant improvement of anxiety level between T0 and T1was observed in the group with Voix d'Or(®) compared to the control group. This study suggests that this non-pharmacological intervention may be beneficial on anxiety in patients with Alzheimer's disease. PMID:24026135

  12. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Khaled; Mohamed; Mohamed; Koriem

    2015-01-01

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

  13. Numerical simulation of antiarrhythmic drugs effects on cardiac action potential

    Převorovská, Světlana; Maršík, František

    Brno : Brno University of Technology, 2006 - (Burša, J.; Fuis, V.), s. 170-171 ISBN 80-214-3232-2. [ Human Biomechanics 2006. Hrotovice (CZ), 13.11.2006-16.11.2006] R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : human cardiovascular system * cardiac action potential * antiarrhytmmic drugs-cell channel interaction Subject RIV: BK - Fluid Dynamics

  14. Differences in pharmacology of tumor necrosis factor (TNF antagonists

    S. Bombardieri

    2011-09-01

    Full Text Available The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.. The differences in their molecular structure, mechanism of action, pharmacokinetics (PK and pharmacodynamics (PD are discussed, along with the differences concerning dose, administration regimens, drug concentrations and pharmacological interactions. In order to explain the clinical differences observed when these agents are used in the “real world”, which can arise from the respective PK characteristics (kinetics, route and frequency of administration, type of TNF binding, effects on cytokines and PD responses and peculiar mechanisms of action, with distinctive immune function (LFTa inactivation; apoptosis induction, TNF immunoprecipitation, C1q binding and CDC induction; Fcg cross-linking and ADCC induction, the dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.

  15. More evidence for a refined Gribov-Zwanziger action based on an effective potential approach

    Vandersickel, N.; Dudal, D.; Sorella, S.P.

    2011-01-01

    The purpose of this proceeding is twofold. Firstly, we shall make the refining of the Gribov-Zwanziger action more complete by taking into account more condensates than considered so far. Secondly, we shall provide more evidence for the refined Gribov-Zwanziger action based on an effective potential approach.

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

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

    2016-07-01

    Noise coming from urban traffic, household appliances or discotheques might be as hazardous to the health of exposed people as occupational noise, because may likewise cause hearing loss, changes in hormonal, cardiovascular and immune systems and behavioral alterations. Besides, noise can affect sleep, work performance and productivity as well as communication skills. Moreover, exposure to noise can trigger an oxidative imbalance between reactive oxygen species (ROS) and the activity of antioxidant enzymes in different structures, which can contribute to tissue damage. In this review we systematized the information from reports concerning noise effects on cell oxidative balance in different tissues, focusing on auditory and non-auditory structures. We paid specific attention to in vivo studies, including results obtained in adult and developing subjects. Finally, we discussed the pharmacological strategies tested by different authors aimed to minimize the damaging effects of noise on living beings. PMID:26657417

  17. 中药栀子有效成分及药理作用的研究进展%Research Progress in Effective Constituents and Pharmacological Effects of Gardenia Jasminoides

    王亭

    2015-01-01

    中药栀子为茜草科植物栀子的干燥成熟果实,其主要有效成分包括环烯醚萜、栀子黄色素、有机酸等. 现代药理研究表明栀子具有抗炎、解热、镇痛、保肝、利胆、降血脂、抗血栓、神经保护、抗阿尔茨海默病等作用. 本文综述了栀子的有效成分及药理作用,为其深入研究提供参考.%Traditional Chinese medicine"Zhizi" is the dry ripe fruit of Gardenia jasminoides Ellis, which belongs to the family of Rubiaceae. The main effective constituents of gardenia include iridoid, gardenia yellow pigment and organic acid. Modern pharmaco-logical studies showed that the main pharmacological effects of gardenia included anti-inflammatory, antipyretic and analgesic effects, liver protection, cholagogue, antilipidemic effect, antithrombus, nerve protection and anti-Alzheimer' s disease. In this paper, the ef-fective constituents and pharmacological effects of Gardenia jasminoides Ellis were reviewed to provide available information for further research.

  18. Scaling behaviour of the effective chiral action and stability of the chiral soliton

    The effective chiral action is evaluated within a novel improved heat-kernel expansion, which includes gradients of the chiral field in a non-perturbative way. The exact scaling behaviour of the effective action of a localized chiral field with respect to changing its spatial size is found. From this it is proved that the radiatively induced derivative terms cannot absolutely stabilize the chiral soliton against collapsing. The collapsing of the soliton is, however, accompanied by a vanishing of the baryon charge. It is argued that the effective chiral action constrained to a fixed baryon number may still admit stable soliton configurations. (orig.)

  19. In-Out Formalism for One-Loop Effective Actions in QED and Gravity

    Kim, Sang Pyo

    2016-01-01

    The in-out formalism is a systematic and powerful method for finding the effective actions in an electromagnetic field and a curved spacetime provided that the field equation has explicitly known solutions. The effective action becomes complex when pairs of charged particles are produced due to an electric field and curved spacetime. This may lead to a conjecture of one-to-one correspondence between the vacuum polarization (real part) and the vacuum persistence (imaginary part). We illustrate the one-loop effective action in a constant electric field in a Minkowski spacetime and in a uniform electric field in a two-dimensional (anti-) de sitter space.

  20. System markets: Indirect network effects in action, or inaction?

    J.L.G. Binken (Jeroen)

    2010-01-01

    textabstractIn this dissertation, I empirically examine system markets up close. More specifically I examine indirect network effects, both demand-side and supply-side indirect network effects. Indirect network effects are the source of positive feedback in system markets, or so network effect theo

  1. Effective actions for the SU(2) confinement-deconfinement phase transition

    We compare different Polyakov-loop actions yielding effective descriptions of finite-temperature SU(2) Yang-Mills theory on the lattice. The actions are motivated by a simultaneous strong coupling and character expansion obeying center symmetry and include both Ising and Ginzburg-Landau type models. To keep things simple we limit ourselves to nearest-neighbor interactions. Some truncations involving the most relevant characters are studied within a novel mean-field approximation. Using inverse Monte Carlo techniques based on exact geometrical Schwinger-Dyson equations we determine the effective couplings of the Polyakov-loop actions. Monte Carlo simulations of these actions reveal that the mean-field analysis is a fairly good guide to the physics involved. Our Polyakov-loop actions reproduce standard Yang-Mills observables well up to limitations due to the nearest-neighbor approximation

  2. Pharmacologic Therapies in Anticoagulation.

    Ferreira, Joana Lima; Wipf, Joyce E

    2016-07-01

    Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611

  3. Action time effect of lime on its depressive ability for pyrite

    Tichang Sun

    2004-01-01

    Two sample groups of bulk concentrates consisting mainly of pyrite and chalcopyrite from Daye and Chenghchao Mines in Hubei Province of China were used to investigate the effect of the action time of lime on its depressive ability for pyrite. The experimental results conducted with different samples and collectors showed that the action time between lime and pyrite markedly influences the depressive ability of lime. The depressive ability of lime increased with the action time increasing. It was also proved that the depressive results obtained at a large lime dosage after a shorter action time are similar to those obtained at a small lime dosage after a longer action time. The increase of depressive ability of lime after a longer action time is because that there are different mechanisms in different action time. The composition on the surface of pyrite acted for different time with lime was studied by using ESCA (Electron Spectroscopic Chemical Analysis). The results showed that iron hydroxide and calcium sulphate formed on the pyrite surface at the presence of lime in the pulp but the amounts of iron hydroxide and calcium sulphate were different at different action time. At the beginning action time the compound formed on the pyrite surface was mainly calcium sulphate and almost no iron hydroxide formed; but with the action time increasing, iron hydroxide formed. The longer the action time, the more iron hydroxide and the less calcium sulphate formed. It was considered that the stronger depressive ability of lime after a longer action time is because more iron hydroxide forms on the pyrite surface.

  4. System markets: Indirect network effects in action, or inaction?

    Binken, Jeroen

    2010-01-01

    textabstractIn this dissertation, I empirically examine system markets up close. More specifically I examine indirect network effects, both demand-side and supply-side indirect network effects. Indirect network effects are the source of positive feedback in system markets, or so network effect theory tells us. Systems are composed of complementary and interdependent products, such as hardware and software. For instance, a video game system is composed of the video game console, on the one han...

  5. Pharmacologic considerations for Shuttle astronauts

    Santy, Patricia A.; Bungo, Michael W.

    1991-01-01

    Medication usage by crewmembers in the preflight and inflight mission periods is common in the Shuttle Program. The most common medical reports for which medication is used are: space motion sickness (SMS), sleeplessness, headache, and backache. A number of medications are available in the Shuttle Medical Kit to treat these problems. Currently, astronauts test all frequently used medications before mission assignment to identify potential side-effects, problems related to performance, personal likes/dislikes, and individual therapeutic effect. However, microgravity-induced changes in drug pharmacokinetics, in combination with multiple operational factors, may significantly alter crewmember responses inflight. This article discusses those factors that may impact pharmacologic efficacy during Shuttle missions.

  6. Leadership: Improving Its Effectiveness. Research Action Brief Number 1.

    ERIC Clearinghouse on Educational Management, Eugene, OR.

    This brief summarizes the major findings of significant research studies dealing with different leadership behaviors and strategies for increasing leadership effectiveness. Fred Fiedler's Contingency Theory of Leadership Effectiveness emphasizes that a leader's effectiveness is determined by how well his leadership style fits the specific…

  7. Characteristics of Effective Training: Developing a Model To Motivate Action.

    Wise, Dena; Ezell, Patsy

    2003-01-01

    The Parenting and Consumer Education project identified effective models for training welfare-to-work facilitators. Premises were the importance of process, learner responsibility, and improvement of social networks. Effective training was learner focused, inspiring, and motivating; demonstrated productive behaviors and effective life skills; and…

  8. Fight against the greenhouse effect. From the local to the international action

    In the fight against the greenhouse gases emissions, the local government are directly concerned. This sheet aims to explain the greenhouse effect, the kyoto protocol, the french national policy and to orientate the local actions. (A.L.B.)

  9. The generalized Schwinger-DeWitt technique and the unique effective action in quantum gravity

    The purpose of this talk is to discuss how one can define and compute the effective action. The authors consider the following subjects: 1. The parameterization-independent and gauge-independent definition of the effective action in QFT. 2. Extension of the Schwinger-DeWitt technique to nonminimal operators, higher-order operators and higher loop orders. The method of generating functional traces. 3. Summation of the proper-time series. Nonlocal terms in the effective action. 4. Applications. The complete algorithm for divergences of a fourth-order operator. The calculational technique for the unique effective action in gauge theories. The unique counterterms for Einstein's theory. Covariant calculation of divergences in two-loop graphs and the absence of leading divergences in two-loop quantum gravity

  10. Mechanism and Effectiveness of Reduction Action of Unsaturated Polyester Resin Reducer

    2001-01-01

    The reduction action mechanism of unsaturated polyester resin reducer is analysed.The experimental results show that the active reducer bearing reactive functional group on the ends of molecules effectively lowers the curing shrinkage of unvaturated polyester resin.

  11. T-duality in the string theory effective action with a string source

    Nurmagambetov, Alexei

    2001-01-01

    We consider the T-duality transformations of the low-energy quantum string theory effective action in the presence of classical fundamental string source and demonstrate explicitly that T-duality still holds.

  12. A Conformal Fixed-Point Equation for the Effective Average Action

    Rosten, Oliver J

    2016-01-01

    A Legendre transform of the recently discovered conformal fixed-point equation is constructed, providing an unintegrated equation encoding full conformal invariance within the framework of the effective average action.

  13. Mitochondrial biogenesis: pharmacological approaches.

    Valero, Teresa

    2014-01-01

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

  14. 中药姜黄主要有效成分药理学研究进展%Pharmacological Research Progress of Main Effective Components of Turmeric

    付兴会; 林连美

    2015-01-01

    中药姜黄因其主要有效成份具有降血脂、抗肿瘤、抗炎等作用,近年来备受关注,有关其药理学研究层出不穷,笔者搜索了万方、知网等数据库的大量相关文献,现将其综述如下,供广大医学者参考学习。%s:Chinese turmeric because of its main effective components has the function of reducing blood fat, anti tumor, anti inflamma-tion, has attracted much attention in recent years, about the pharmacological study on different layer, the author search Wan Fang, HowNet database such as a large number of documents, the review is as follows, for the majority of medical reference learning.

  15. Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension

    Bendtsen, Flemming; Brinch, K; Møller, Søren; Henriksen, Jens Henrik Sahl; Becker, Povl Ulrik; Hansen, Erik Feldager

    2001-01-01

    technique were compared in 20 patients with portal hypertension. The ability of EUS flowmetry to detect changes in the azygos and portal venous flow after an intravenous dose of 2 mg of terlipressin was evaluated in 13 of the patients in a double-blind, randomized, placebo-controlled, cross-over design......BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow measurements by means of the Doppler technique. The aim of the study was to evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS: Measurements of azygos blood flow by EUS and by the thermodilution...... measurement of the azygos blood flow correlate strongly to the measurements by the thermodilution technique, and EUS is moreover well tolerated by the patients. The method is applicable for monitoring pharmacological effects on the superior porto-systemic collateral circulation and portal venous flow in...

  16. The four-loop string effective action from the bosonic σ-model

    We discuss the formulation of the string effective action, in terms of quantities defined within the bosonic σ-model, at four loops or O(α'4). In particular we show that a recent construction given by Osborn correctly yields the effective action at this order for the minimal subtraction renormalisation scheme. We demonstrate a renormalisation scheme for which Osborn's action reduces to a simpler form proposed by Tseytlin at this order. As part of our analysis, we calculate, using indirect methods, various O(α'4) quantities for the σ-model, in particular the five-loop dilaton β-function. (orig.)

  17. Pharmacological hypothermia: a potential for future stroke therapy?

    Liu, Kaiyin; Khan, Hajra; Geng, Xiaokun; Zhang, Jun; Ding, Yuchuan

    2016-06-01

    Mild physical hypothermia after stroke has been associated with positive outcomes. Despite the well-studied beneficial effects of hypothermia in the treatment of stroke, lack of precise temperature control, intolerance for the patient, and immunosuppression are some of the reasons which limit its clinical translation. Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models. Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives. Interestingly, drugs in the TRPV1, neurotensin, and thyroxine families have been shown to have effects in thermoregulatory control in decreasing the compensatory hypothermic response during cooling. This review will briefly present drugs in the eight classes by summarizing their proposed mechanisms of action as well as side effects. Reported thermoregulatory effects of the drugs will also be presented. This review offers the opinion that these agents may be useful in combination therapies with physical hypothermia to achieve faster and more stable temperature control in hypothermia. PMID:27320243

  18. The Quantum Consistency of the Ten-Dimensional Heterotic String Effective Action

    Simon Davis

    2011-01-01

    The finiteness of superstring theory at each order in perturbation theory is considered with respect to the ten-dimensional effective action. The quantum consistency of the ten-dimensional superstring effective action is confirmed with an analysis of the perturbative expansion of the quartic sector. It is found to be compatible with the finiteness of reduced four-dimensional theory. Furthermore, implications for the validity of superstring perturbation theory at lower energies is considered.

  19. Effect of Action Verbs on the Performance of a Complex Movement

    Rabahi, Tahar; Fargier, Patrick; Rifai Sarraj, Ahmad; Clouzeau, Cyril; Massarelli, Raphael

    2013-01-01

    The interaction between language and motor action has been approached by studying the effect of action verbs, kinaesthetic imagery and mental subtraction upon the performance of a complex movement, the squat vertical jump (SVJ). The time of flight gave the value of the height of the SVJ and was measured with an Optojump® and a Myotest® apparatuses. The results obtained by the effects of the cognitive stimuli showed a statistically significant improvement of the SVJ performance after either lo...

  20. Effect of action verbs on the performance of a complex movement.

    Tahar Rabahi

    Full Text Available The interaction between language and motor action has been approached by studying the effect of action verbs, kinaesthetic imagery and mental subtraction upon the performance of a complex movement, the squat vertical jump (SVJ. The time of flight gave the value of the height of the SVJ and was measured with an Optojump® and a Myotest® apparatuses. The results obtained by the effects of the cognitive stimuli showed a statistically significant improvement of the SVJ performance after either loudly or silently pronouncing, hearing or reading the verb saute (jump in French language. Action verbs specific for other motor actions (pince = pinch, lèche = lick or non-specific (bouge = move showed no or little effect. A meaningless verb for the French subjects (tiáo = jump in Chinese showed no effect as did rêve (dream, tombe (fall and stop. The verb gagne (win improved significantly the SVJ height, as did its antonym perds (lose suggesting a possible influence of affects in the subjects' performance. The effect of the specific action verb jump upon the heights of SVJ was similar to that obtained after kinaesthetic imagery and after mental subtraction of two digits numbers from three digits ones; possibly, in the latter, because of the intervention of language in calculus. It appears that the effects of the specific action verb jump did seem effective but not totally exclusive for the enhancement of the SVJ performance. The results imply an interaction among language and motor brain areas in the performance of a complex movement resulting in a clear specificity of the corresponding action verb. The effect upon performance may probably be influenced by the subjects' intention, increased attention and emotion produced by cognitive stimuli among which action verbs.