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Sample records for action pharmacology effects

  1. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

    Science.gov (United States)

    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

  2. Pharmacological Effects of Biotin in Animals.

    Science.gov (United States)

    Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

    2017-01-01

    In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Studies on the pharmacological action of cactus: identification of its anti-inflammatory effect.

    Science.gov (United States)

    Park, E H; Kahng, J H; Paek, E A

    1998-02-01

    The ethanol extracts of Opuntia ficus-indica fructus (EEOF) and Opuntia ficus-indica stem (EEOS) were prepared and used to evaluate the pharmacological effects of cactus. Both the extracts inhibited the writhing syndrome induced by acetic acid, indicating that they contains analgesic effect. The oral administrations of EEOF and EEOS suppressed carrageenan-induced rat paw edema and also showed potent inhibition in the leukocyte migration of CMC-pouch model in rats. Moreover, the extracts suppressed the release of beta-glucuronidase, a lysosomal enzyme in rat neutrophils. It was also noted that the extracts showed the protective effect on gastric mucosal layers. From the results it is suggested that the cactus extracts contain anti-inflammatory action having protective effect against gastric lesions.

  4. Proteomic Contributions to Medicinal Plant Research: From Plant Metabolism to Pharmacological Action

    Directory of Open Access Journals (Sweden)

    Akiko Hashiguchi

    2017-12-01

    Full Text Available Herbal medicine is a clinical practice of utilizing medicinal plant derivatives for therapeutic purposes. It has an enduring history worldwide and plays a significant role in the fight against various diseases. Herbal drug combinations often exhibit synergistic therapeutic action compared with single-constituent dosage, and can also enhance the cytotoxicity induced by chemotherapeutic drugs. To explore the mechanism underlying the pharmacological action of herbs, proteomic approaches have been applied to the physiology of medicinal plants and its effects on animals. This review article focuses on the existing proteomics-based medicinal plant research and discusses the following topics: (i plant metabolic pathways that synthesize an array of bioactive compounds; (ii pharmacological action of plants tested using in vivo and in vitro studies; and (iii the application of proteomic approaches to indigenous plants with scarce sequence information. The accumulation of proteomic information in a biological or medicinal context may help in formulating the effective use of medicinal plants.

  5. Pharmacological effects of biotin.

    Science.gov (United States)

    Fernandez-Mejia, Cristina

    2005-07-01

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

  6. Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline.

    Science.gov (United States)

    Shi, Jing-Shan; Yu, Jun-Xian; Chen, Xiu-Ping; Xu, Rui-Xia

    2003-02-01

    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.

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

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

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

  8. Pharmacological effects and potential therapeutic targets of DT-13.

    Science.gov (United States)

    Khan, Ghulam Jilany; Rizwan, Mohsin; Abbas, Muhammad; Naveed, Muhammad; Boyang, Yu; Naeem, Muhammad Ahsan; Khan, Sara; Yuan, Shengtao; Baig, Mirza Muhammad Faran Ashraf; Sun, Li

    2018-01-01

    DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies. In vivo and in vitro studies show that the drug regulates multiple cellular functions for its several pharmacological effects including, anti-adhesive effects via regulation of tissue factor and transforming growth factor; anti-migratory effects through indirect regulation of NM-IIA in the tumor microenvironment, Tissue factor, down-regulation of CCR5-CCL5 axis and MMP-2/9 inhibition; anti-metastatic effects via regulation of MMPs and tissue factor; pro-apoptotic effects by modulation of endocytosis of EGF receptor; anti-angiogenic effects via regulation of HIF-1α,ERK, Akt signalling and autophagy inducing characteristics by regulating PI3K/Akt/mTOR signalling pathway. In addition to anti-tumor activities, DT-13 has significant anti-inflammatory, cardioprotective, hepatoprotective and immunomodulating effects. Pharmaceutical dosage form and targeted drug delivery system for DT-13 has not been established yet. Moreover, DT-13, has not been studied for its action on brain, colorectal, hepatic, pancreatic, prostate and blood cancers. Similarly the effects of drug on carbohydrate and glucose metabolism is another niche yet to be explored. In some traditional therapies, crude drug from the plant is used against diabetic and neurological disorders that are not reported in scientific literature, however due to profound effects of

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

    Science.gov (United States)

    Sundarrajan, Sudharsana; Lulu, Sajitha; Arumugam, Mohanapriya

    2017-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Cardiovascular Pharmacology of Sinomenine: The Mechanical and Electropharmacological Actions

    Directory of Open Access Journals (Sweden)

    Seiichiro Nishida

    2007-01-01

    Full Text Available Sinomenine is one of the alkaloids extracted from Chinese medical plant, Sinomenium acutum Rehder et Wilson. Sinomenine has been used for Rheumatoid arthritis as an anti-inflammatory and immunomodulative drugs. We have so far been investigated the cardiovascular pharmacological actions of sinomenine. Sinomenine dilated NE (5 μM-, KCl (60 mM- and PDB (300 nM-induced vasoconstrictions. The pretreatment with nicardipine (0.1 μM, staurosporine (30 nM, L-NMMA (100 μM, indomethacin (10 μM or propranolol significantly attenuated the sinomenine-induced vasorelaxation. Therefore, these results indicate that sinomenine causes the vasorelaxation by the involvement with the inhibitions of Ca 2+ current (I Ca and PK-C, β-adrenoceptor stimulation, and the activation of NO and PGI 2 syntheses in endothelium. On the other hand, in the ventricular cardiomyocytes of guinea pig, sinomenine inhibits I Ca and simultaneously decreases the delayed rectifier K + current (I K , resulting in the prolongation of action potential duration. Sinomenine also suppresses the dysrhysmias induced by triggered activities under the Ca 2+ overload condition. Therefore, sinomenine may be expected as one of effective therapeutic drugs for heart failure and dysrhythmias, and may maintain the cardiovascular functions due to modulation of cardiac ionic channels and blood vessels.

  12. Dysport: pharmacological properties and factors that influence toxin action.

    Science.gov (United States)

    Pickett, Andy

    2009-10-01

    The pharmacological properties of Dysport that influence toxin action are reviewed and compared with other botulinum toxin products. In particular, the subject of diffusion is examined and discussed based upon the evidence that currently exists, both from laboratory studies and from clinical data. Diffusion of botulinum toxin products is not related to the size of the toxin complex in the product since the complex dissociates under physiological conditions, releasing the naked neurotoxin to act. The active neurotoxin in Type A products is the same and therefore diffusion is equal when equal doses are administered.

  13. Pharmacological effects of two cytolysins isolated from the sea ...

    Indian Academy of Sciences (India)

    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.

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

    Science.gov (United States)

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

    2016-11-23

    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

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

    International Nuclear Information System (INIS)

    Qureshi, M.A.; Mahmood, A.

    2011-01-01

    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)

  16. Pharmacological Effects of Niacin on Acute Hyperlipemia.

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Danilo De Gregorio

    2016-11-01

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

  18. [Ibogaine--the substance for treatment of toxicomania. Neurochemical and pharmacological action].

    Science.gov (United States)

    Kazlauskas, Saulius; Kontrimaviciūte, Violeta; Sveikata, Audrius

    2004-01-01

    The review of scientific literature, concerning the indol alkaloid Ibogaine, which is extracted from the bush Tabernanthe Iboga, is presented in this article. Used as a stimulating factor for hundred of years in non-traditional medicine, this alkaloid could be important for modern pharmacology because of potential anti-addictive properties. The mechanism of action of this alkaloid is closely related to different neurotransmitting systems. Studies with animals allow concluding that Ibogaine or medicines based on this alkaloid can be used for treatment of drug dependencies.

  19. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

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

  20. Portulaca oleracea L.: a review of phytochemistry and pharmacological effects.

    Science.gov (United States)

    Zhou, Yan-Xi; Xin, Hai-Liang; Rahman, Khalid; Wang, Su-Juan; Peng, Cheng; Zhang, Hong

    2015-01-01

    Portulaca oleracea L., belonging to the Portulacaceae family, is commonly known as purslane in English and Ma-Chi-Xian in Chinese. It is a warm-climate, herbaceous succulent annual plant with a cosmopolitan distribution. It is eaten extensively as a potherb and added in soups and salads around the Mediterranean and tropical Asian countries and has been used as a folk medicine in many countries. Diverse compounds have been isolated from Portulaca oleracea, such as flavonoids, alkaloids, polysaccharides, fatty acids, terpenoids, sterols, proteins vitamins and minerals. Portulaca oleracea possesses a wide spectrum of pharmacological properties such as neuroprotective, antimicrobial, antidiabetic, antioxidant, anti-inflammatory, antiulcerogenic, and anticancer activities. However, few molecular mechanisms of action are known. This review provides a summary of phytochemistry and pharmacological effects of this plant.

  1. Pharmacological considerations for predicting PK/PD at the site of action for therapeutic proteins.

    Science.gov (United States)

    Wang, Weirong; Zhou, Honghui

    For therapeutic proteins whose sites of action are distal to the systemic circulation, both drug and target concentrations at the tissue sites are not necessarily proportional to those in systemic circulation, highlighting the importance of understanding pharmacokinetic/pharmacodynamic (PK/PD) relationship at the sites of action. This review summarizes the pharmacological considerations for predicting local PK/PD and the importance of measuring PK and PD at site of action. Three case examples are presented to show how mechanistic and physiologically based PK/PD (PBPK/PD) models which incorporated the PK and PD at the tissue site can be used to facilitate understanding the exposure-response relationship for therapeutic proteins. Copyright © 2016. Published by Elsevier Ltd.

  2. A novel systems pharmacology platform to dissect action mechanisms of traditional Chinese medicines for bovine viral diarrhea disease.

    Science.gov (United States)

    Zheng, Chunli; Pei, Tianli; Huang, Chao; Chen, Xuetong; Bai, Yaofei; Xue, Jun; Wu, Ziyin; Mu, Jiexin; Li, Yan; Wang, Yonghua

    2016-10-30

    Due to the large direct and indirect productivity losses in the livestock industry caused by bovine viral diarrhea (BVD) and the lack of effective pharmacological therapies, developing an efficient treatment is extremely urgent. Traditional Chinese medicines (TCMs) that simultaneously address multiple targets have been proven to be effective therapies for BVD. However, the potential molecular action mechanisms of TCMs have not yet been systematically explored. In this work, take the example of a herbal remedy Huangqin Zhizi (HQZZ) for BVD treatment in China, a systems pharmacology approach combining with the pharmacokinetics and pharmacodynamics evaluation was developed to screen out the active ingredients, predict the targets and analyze the networks and pathways. Results show that 212 active compounds were identified. Utilizing these lead compounds as probes, we predicted 122 BVD related-targets. And in vitro experiments were conducted to evaluate the reliability of some vital active compounds and targets. Network and pathway analysis displayed that HQZZ was effective in the treatment of BVD by inhibiting inflammation, enhancing immune responses in hosts toward virus infection. In summary, the analysis of the complete profile of the pharmacological activities, as well as the elucidation of targets, networks and pathways can further elucidate the underlying anti-inflammatory, antiviral and immune regulation mechanisms of HQZZ against BVD. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Lucius eCaviola

    2015-12-01

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

  5. What is a food and what is a medicinal product in the European Union? Use of the benchmark dose (BMD) methodology to define a threshold for "pharmacological action".

    Science.gov (United States)

    Lachenmeier, Dirk W; Steffen, Christian; el-Atma, Oliver; Maixner, Sibylle; Löbell-Behrends, Sigrid; Kohl-Himmelseher, Matthias

    2012-11-01

    The decision criterion for the demarcation between foods and medicinal products in the EU is the significant "pharmacological action". Based on six examples of substances with ambivalent status, the benchmark dose (BMD) method is evaluated to provide a threshold for pharmacological action. Using significant dose-response models from literature clinical trial data or epidemiology, the BMD values were 63mg/day for caffeine, 5g/day for alcohol, 6mg/day for lovastatin, 769mg/day for glucosamine sulfate, 151mg/day for Ginkgo biloba extract, and 0.4mg/day for melatonin. The examples for caffeine and alcohol validate the approach because intake above BMD clearly exhibits pharmacological action. Nevertheless, due to uncertainties in dose-response modelling as well as the need for additional uncertainty factors to consider differences in sensitivity within the human population, a "borderline range" on the dose-response curve remains. "Pharmacological action" has proven to be not very well suited as binary decision criterion between foods and medicinal product. The European legislator should rethink the definition of medicinal products, as the current situation based on complicated case-by-case decisions on pharmacological action leads to an unregulated market flooded with potentially illegal food supplements. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Anesthetic pharmacology

    National Research Council Canada - National Science Library

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio; Khalil, Omar Arafat Kdudsi; Carvalho, Claudio Teodoro de; Bannach, Gilbert

    2011-01-01

    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)

  8. Fraxinus: A Plant with Versatile Pharmacological and Biological Activities.

    Science.gov (United States)

    Sarfraz, Iqra; Rasul, Azhar; Jabeen, Farhat; Younis, Tahira; Zahoor, Muhammad Kashif; Arshad, Muhammad; Ali, Muhammad

    2017-01-01

    Fraxinus , a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications.

  9. Pharmacological Experimental Study Of The Anti-Depressant Effect ...

    African Journals Online (AJOL)

    Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

  10. Structure and pharmacological actions of phyllocaerulein, a caerulein-like nonapeptide

    Science.gov (United States)

    Anastasi, A.; Bertaccini, G.; Cei, J. M.; De Caro, G.; Erspamer, V.; Impicciatore, M.

    1969-01-01

    1. The South American amphibian Phyllomedusa sauvagei contains in its skin large amounts of a polypeptide closely resembling caerulein in its pharmacological actions. This polypeptide, called phyllocaerulein, was obtained in a pure form, and upon acid hydrolysis, enzymic digestion and end-group determination experiments it proved to be a nonapeptide of the following composition Pyr-Glu-Tyr(SO3H)-Thr-Gly-Trp-Met-Asp-Phe-NH2 It may be seen that caerulein and phyllocaerulein have in common the C-terminal heptapeptide and the N-terminal pyroglutamyl residue. 2. Phyllocaerulein is indistinguishable from caerulein even in parallel bioassay. However, the former polypeptide seems to be somewhat more potent than the latter on all the preparations tested. 3. In different batches of Phyllomedusa sauvagei skin the phyllocaerulein content ranged between 150 and 600 μg/g of fresh tissue. Phyllocaerulein or similar polypeptides occur also in the skin of several other Phyllomedusa species, among which are Phyll. burmeisteri, Phyll. dachnicolor, Phyll, helenae, Phyll. annae, Phyll. callidryas and Phyll. bicolor. 4. The qualitative identification and quantitative estimation of caerulein-like polypeptides in crude skin extracts may be complicated by the concomitant occurrence of other active polypeptides. These, however, are poorly effective on some test preparations which seem to respond selectively to caerulein. 5. Like that of caerulein, the biological significance of phyllocaerulein is completely obscure. PMID:5824931

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

    Science.gov (United States)

    Suzuki, Mayumi; Ito, Yoshihiko; Fujino, Tomomi; Abe, Masayuki; Umegaki, Keizo; Onoue, Satomi; Noguchi, Hiroshi; Yamada, Shizuo

    2009-03-01

    Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic 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 5alpha-reductase. Today, alpha(1)-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 relevant receptors in the lower urinary tract, such as alpha(1)-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine receptors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of alpha(1)-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 understanding of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms (LUTS).

  12. Pharmacological Properties of Melanin and its Function in Health.

    Science.gov (United States)

    ElObeid, Adila Salih; Kamal-Eldin, Afaf; Abdelhalim, Mohamed Anwar K; Haseeb, Adil M

    2017-06-01

    The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photoprotective and immunological action, are well recognized. Its antioxidant, anti-inflammatory, immunomodulatory, radioprotective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognized and studied. It is also associated with certain disorders of the nervous system. In this MiniReview, we consider the steadily increasing literature on the bioavailability and functional activity of melanin. Published literature shows that melanin may play a number of possible pharmacological effects such as protective, stimulatory, diagnostic and curative roles in human health. In this MiniReview, possible health roles and pharmacological effects are considered. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  13. Pharmacological activities of Vitex agnus-castus extracts in vitro.

    Science.gov (United States)

    Meier, B; Berger, D; Hoberg, E; Sticher, O; Schaffner, W

    2000-10-01

    The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

  14. [Study on pharmacologic action characteristics of traditional Chinese medicines distributed along liver meridian based on medicinal properties combinations].

    Science.gov (United States)

    Guo, Hong-Ling; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    To establish a characterization system of traditional Chinese medicinal properties in line with modern scientific cognition regularity, in order to reveal properties of traditional Chinese medicines distributed along liver meridian and relations of effects of medicinal properties. By collecting data about traditional Chinese medicinal properties recorded in the Pharmacopoeia of the People's Republic of China (2005 Edition), literature and data about pharmacological effects of traditional Chinese medicines recorded in the Chinese Materia Medica, by using the method of association rules, the authors dug pharmacological effect rules corresponds to relevant medicinal property combinations, with the medicinal property combination of traditional Chinese medicines distributed along liver meridian as the target. It was found that either obvious different pharmacological effects or identical pharmacological characteristics existed in traditional Chinese medicines distributed along liver meridian. With the aim to explore the correlations between traditional Chinese medicine medicinal properties and pharmacological effects, the authors linked the traditional Chinese medicine theory with modern research achievements, in order to provide the ideas and methods for interpreting mechanisms of medicinal properties.

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  18. Pharmacological Aspects of Neuro-Immune Interactions.

    Science.gov (United States)

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

    2018-01-01

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

  19. 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).

    Science.gov (United States)

    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)

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

    Directory of Open Access Journals (Sweden)

    Caroline Addison Carvalho Xavier

    2008-01-01

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

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

    Science.gov (United States)

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

    2008-05-08

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

  2. Pharmacological analysis of paregoric elixir and its constituents: in vitro and in vivo studies.

    Science.gov (United States)

    Andrade, Edinéia Lemos; Ferreira, Juliano; Santos, Adair R S; Calixto, João B

    2007-11-01

    Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross-tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents.

  3. Apomorphine and piribedil in rats: biochemical and pharmacologic studies.

    Science.gov (United States)

    Butterworth, R F; Poignant, J C; Barbeau, A

    1975-01-01

    We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less

  4. Pharmacological interventions to treat phlebitis: systematic review.

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    Bondarchuk, N G; Fisenko, V P

    2016-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  7. Recent Pharmacology Studies on the International Space Station

    Science.gov (United States)

    Wotring, Virginia

    2014-01-01

    The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during long-duration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.

  8. The Genus Spilanthes Ethnopharmacology, Phytochemistry, and Pharmacological Properties: A Review

    Science.gov (United States)

    Paulraj, Jayaraj; Govindarajan, Raghavan; Palpu, Pushpangadan

    2013-01-01

    Spilanthes spp. are popular, over-the-counter remedies; they are sold over the internet under various names and are widely used in traditional medicine in various cultures. This review will summarize the important reports on the ethnopharmacology, botany, phytochemistry, and pharmacological properties as described in the literature from recent years (1920 to 2013). Spilanthes spp. are used for more than 60 types of disorders. They are reported to contain a number of biologically active phytochemicals, although a large number of ethnopharmacological uses have been documented; only a few of these species have been investigated for their chemical and biological activities. The studies are carried out mainly on Spilanthes extracts and a few metabolites substantiate the uses of these plants in traditional medicine. Well-conducted pharmacological studies are still needed for several traditional indications, and the mechanisms of action by which the plant extracts and the active compounds exert their pharmacological effects remain to be studied. They are predominantly used as extracts in personal care products, traditional medicines, and the pharmaceutical and culinary areas. Suggestions are made regarding some of the possible mechanisms of action as to how the known compounds may exert their biological activity. PMID:24454346

  9. [Advances in research of chemical constituents and pharmacological activities of common used spices].

    Science.gov (United States)

    Sun, Chao-nan; Zhu, Yuan; Xu, Xi-ming; Yu, Jiang-nan

    2014-11-01

    Spices have enjoyed a long history and a worldwide application. Of particular interest is the pharmaceutical value of spices in addition to its basic seasoning function in cooking. Concretely, equipped with complex chemical compositions, spices are of significant importance in pharmacologic actions, like antioxidant, antibacterial, antitumor, as well as therapeutical effects in gastrointestinal disorders and cardiovascular disease. Although increasing evidences in support of its distinct role in the medical field has recently reported, little information is available for substantive, thorough and sophisticated researches on its chemical constituents and pharmacological activities, especially mechanism of these actions. Therefore, in popular wave of studies directed at a single spice, this review presents systematic studies on the chemical constituents and pharmacological activities associated with common used spices, together with current typical individual studies on functional mechanism, in order to pave the way for the exploitation and development of new medicines derived from the chemical compounds of spice (such as, piperine, curcumin, geniposide, cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic acid, crocin).

  10. How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

    Science.gov (United States)

    Yuan, Haidan; Ma, Qianqian; Cui, Heying; Liu, Guancheng; Zhao, Xiaoyan; Li, Wei; Piao, Guangchun

    2017-07-07

    Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.

  11. Systems pharmacology - Towards the modeling of network interactions.

    Science.gov (United States)

    Danhof, Meindert

    2016-10-30

    Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity. Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior. Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). In this contribution it is shown how physiology-based PKPD and

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

    Science.gov (United States)

    White, C Michael

    2017-03-01

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

  13. Basic pharmacology of topical imiquimod, 5-fluorouracil, and diclofenac for the dermatologic surgeon.

    Science.gov (United States)

    Desai, Tejas; Chen, Cynthia L; Desai, Alpesh; Kirby, William

    2012-01-01

    Ultraviolet radiation (UVR) contributes to the vast majority of nonmelanoma skin cancer (NMSC). As the incidence of NMSC continues to rise, topical therapies will be used with increasing frequency. Topical therapies may benefit high-risk surgical candidates as an alternative treatment modality and may improve overall cosmesis. The most commonly employed topical therapies are imiquimod, 5-fluorouracil (5-FU), and diclofenac. To review the detailed mechanism of action and side-effect profiles of each topical therapy used to treat NMSC and to explore newly discovered actions. Uncommon adverse events are also presented. An extensive literature search was performed to describe the pharmacologic actions of imiquimod, 5-FU, and diclofenac. A keen understanding of the pharmacologic concepts of these topical therapies may aid the dermatologic surgeon in making sound choices before, during, and after surgery. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Alejandro M. S. Mayer

    2017-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Gaultheria: Phytochemical and Pharmacological Characteristics

    Directory of Open Access Journals (Sweden)

    Ren-Bing Shi

    2013-09-01

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

  17. Pharmacological study on traditional Chinese medicine and natural product in China

    Institute of Scientific and Technical Information of China (English)

    Yong-xiang ZHANG

    2017-01-01

    China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to

  18. A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2017-03-01

    Full Text Available Radix salviae miltiorrhizae (Danshen in Chinese, a classic traditional Chinese medicine (TCM herb, has been used for centuries to treat liver diseases. In this study, the preventive and curative potential of Danshen aqueous extract on acute/chronic alcoholic liver disease (ALD and non-alcoholic fatty liver disease (NAFLD was studied. The in vivo results indicated that Danshen could alleviate hepatic inflammation, fatty degeneration, and haptic fibrogenesis in ALD and NAFLD models. In the aspect of mechanism of action, the significant reduction in MDA levels in both ALD and NAFLD models implies the decreased levels of oxidative stress by Danshen. However, Danshen treatment could not activate the internal enzymatic antioxidant system in ALD and NAFLD models. To further explore the hepatoprotective mechanism of Danshen, an in silico-based network pharmacology approach was employed in the present study. The pharmacological network analysis result revealed that six potential active ingredients such as tanshinone iia, salvianolic acid b, and Danshensu may contribute to the hepatoprotective effects of Danshen on ALD and NAFLD. The action mechanism may relate with regulating the intracellular molecular targets such as PPARα, CYP1A2, and MMP2 for regulation of lipid metabolism, antioxidant and anti-fibrogenesis by these potential active ingredients. Our studies suggest that the combination of network pharmacology strategy with in vivo experimental study may provide a forceful tool for exploring the mechanism of action of traditional Chinese medicine (TCM herb and developing novel bioactive ingredients.

  19. Pharmacological and other beneficial effects of anti- nutritional ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Key words: Pharmacological, beneficial effects, anti-nutritional factors, plants. INTRODUCTION ...... Rankin SM, DeWhalley CV, Hoult S, Jessup W, Willins GM, Collard J, .... saponins from alfalfa on weeds and wheat. Bot. Bull ...

  20. The effective action

    International Nuclear Information System (INIS)

    DeWitt, B.

    1987-01-01

    The concept of the effective action in quantum field theory was introduced into physics by Julian Schwinger in 1954. The effective action summarizes, in a single functional, all the quantum properties of the fields under consideration. The functional derivative of the effective action yields the effective field equations, which replace the classical field equations as descriptors of the dynamical behavior of quantized fields. Solutions of these equations are 'in-out' matrix elements of the field operators and, when substituted back into the effective action itself, yield logarithms of the corresponding 'in-out' amplitudes. The classical field equations are gauge covariant, a fact that derives from the gauge invariance of the classical action. One has learned how to construct effective actions that are similarly gauge invariant (in each order of perturbation theory) and that yield effective field equations having the covariance properties of their classical analogs. Despite this advance, problems remain, stemming from the fact that there is not one but an infinite number of gauge invariant effective actions, one for every background-covariant choice of supplementary conditions and ghost fields. Vilkovisky (1984) has argued persuasively that by requiring additionally that the effective action be invariant under local invertible changes in the choice of basic field variables, one can construct a natural unique gauge invariant effective action. This lecture will examine Vilkovisky's ideas. 3 refs

  1. Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides.

    Science.gov (United States)

    Dos Santos, Cintia Miranda; Campos, Jaqueline Ferreira; Dos Santos, Helder Freitas; Balestieri, José Benedito Perrella; Silva, Denise Brentan; de Picoli Souza, Kely; Carollo, Carlos Alexandre; Estevinho, Leticia M; Dos Santos, Edson Lucas

    2017-01-01

    Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae . The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

  2. Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

    Directory of Open Access Journals (Sweden)

    Cintia Miranda dos Santos

    2017-01-01

    Full Text Available Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae. The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

  3. Dendrobium officinale Kimura et Migo: A Review on Its Ethnopharmacology, Phytochemistry, Pharmacology, and Industrialization

    Science.gov (United States)

    Tang, Hanxiao; Zhao, Tianwen; Sheng, Yunjie; Zheng, Ting; Fu, Lingzhu

    2017-01-01

    Ethnopharmacological Relevance. Dendrobii Officinalis Caulis, the stems of Dendrobium officinale Kimura et Migo, as a tonic herb in Chinese materia medica and health food in folk, has been utilized for the treatment of yin-deficiency diseases for decades. Methods. Information for analysis of Dendrobium officinale Kimura et Migo was obtained from libraries and Internet scientific databases such as PubMed, Web of Science, Google Scholar, ScienceDirect, Wiley InterScience, Ingenta, Embase, CNKI, and PubChem. Results. Over the past decades, about 190 compounds have been isolated from Dendrobium officinale Kimura et Migo. Its wide modern pharmacological actions in hepatoprotective effect, anticancer effect, hypoglycemic effect, antifatigue effect, gastric ulcer protective effect, and so on were reported. This may mainly attribute to the major and bioactive components: polysaccharides. However, other small molecule components require further study. Conclusions. Due to the lack of systematic data of Dendrobium officinale, it is important to explore its ingredient-function relationships with modern pharmacology. Recently, studies on the chemical constituents of Dendrobium officinale concentrated in crude polysaccharides and its structure-activity relationships remain scant. Further research is required to determine the Dendrobium officinale toxicological action and pharmacological mechanisms of other pure ingredients and crude extracts. In addition, investigation is needed for better quality control and novel drug or product development. PMID:28386292

  4. Pharmacology and function of melatonin receptors

    International Nuclear Information System (INIS)

    Dubocovich, M.L.

    1988-01-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references

  5. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

    Science.gov (United States)

    Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

    2017-04-01

    The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

  6. Cellular and Molecular Targets of Menthol Actions

    Directory of Open Access Journals (Sweden)

    Murat Oz

    2017-07-01

    Full Text Available Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions of menthol. There has been new evidence demonstrating that menthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at least some of the biological and pharmacological effects of menthol can be mediated by alterations in cellular excitability. In this article, we examine the results of earlier studies on the actions of menthol with voltage and ligand-gated ion channels.

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

    Directory of Open Access Journals (Sweden)

    Mohamed Yousif Ibrahim

    2016-05-01

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

  8. Harnessing Big Data for Systems Pharmacology.

    Science.gov (United States)

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

    2017-01-06

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

  9. Pharmacological repositioning of Achyranthes aspera as an antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation.

    Science.gov (United States)

    Goel, R K; Gawande, D Y; Lagunin, A A; Poroikov, V V

    2018-01-01

    Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.

  10. Naloxone : actions of an antagonist

    NARCIS (Netherlands)

    Dorp, Eveline Louise Arianna van

    2009-01-01

    The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

  11. Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

    Directory of Open Access Journals (Sweden)

    Zhong-Rong Zhang

    2015-01-01

    Full Text Available This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl-2H-1-benzopyran-2-one, a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP and cyclic adenosine monophosphate (cGMP level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Boskabady

    2014-01-01

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

  13. Pharmacological treatment of the benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Perez Guerra, Yohani; Molina Cuevas, Vivian; Oyarzabal Yera, Ambar; Mas Ferreiro, Rosa

    2011-01-01

    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 aα 1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5aα-reductase inhibitors, the aα 1 -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 aα 1 -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

  14. 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.

    Science.gov (United States)

    Hadrup, Niels

    2014-08-01

    Mathematical models have been developed for the toxicological risk assessment of chemical mixtures. However, exposure data as well as single chemical toxicological data are required for these models. When addressing this data need, it could be attractive to focus on chemicals with similar mechanisms of action, similar modes of action or with common target organs. In the European Union, efforts are currently being made to subgroup chemicals according to this need. However, it remains to be determined whether this is the best strategy to obtain data for risk assessment. In conditions such as cancer or HIV, it is generally recognised that pharmacological combination therapy targeting different mechanisms of action is more effective than a strategy where only one mechanism is targeted. Moreover, in diseases such as acute myocardial infarction and congestive heart failure, several organ systems concomitantly contribute to the pathophysiology, suggesting that a grouping based on common target organs may also be inefficient. A better option may be to prioritise chemicals on the basis of potency and risk of exposure. In conclusion, there are arguments to suggest that we should concomitantly consider all targets that a chemical can affect in the human body and not merely a subset. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cyclodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: a patent review.

    Science.gov (United States)

    Diniz, Tâmara Coimbra; Pinto, Tiago Coimbra Costa; Menezes, Paula Dos Passos; Silva, Juliane Cabral; Teles, Roxana Braga de Andrade; Ximenes, Rosana Christine Cavalcanti; Guimarães, Adriana Gibara; Serafini, Mairim Russo; Araújo, Adriano Antunes de Souza; Quintans Júnior, Lucindo José; Almeida, Jackson Roberto Guedes da Silva

    2018-01-01

    Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins. Areas covered: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included. Expert opinion: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.

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

    Science.gov (United States)

    Taylor, Johanna; Stubbs, Brendon; Hewitt, Catherine; Ajjan, Ramzi A.; Gilbody, Simon; Holt, Richard I. G.; Hughes, Tom; Kellar, Ian; Mahmoodi, Neda; Smith, Robert D.; Wright, Judy M.; Siddiqi, Najma

    2017-01-01

    People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration’s tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], pfasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design

  17. Cistanches Herba: An overview of its chemistry, pharmacology, and pharmacokinetics property.

    Science.gov (United States)

    Fu, Zhifei; Fan, Xiang; Wang, Xiaoying; Gao, Xiumei

    2018-06-12

    Cistanches Herba is an Orobanchaceae parasitic plant. As a commonly used Traditional Chinese Medicine (TCM), its traditional functions include treating kidney deficiency, impotence, female infertility and senile constipation. Chemical analysis of Cistanches Herba revealed that phenylethanoid glycosides, iridoids, lignans, oligosaccharides, and polysaccharides were the main constituents. Pharmacological studies demonstrated that Cistanches Herba exhibited neuroprotective, immunomodulatory, hormonal balancing, anti-fatigue, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, anti-viral, and anti-tumor effects, etc. The aim of this review is to provide updated, comprehensive and categorized information on the phytochemistry, pharmacological research and pharmacokinetics studies of the major constituents of Cistanches Herba. The literature search was conducted by systematic searching multiple electronic databases including SciFinder, ISI Web of Science, PubMed, Google Scholar and CNKI. Information was also collected from journals, local magazines, books, monographs. To date, more than 100 compounds have been isolated from this genus, include phenylethanoid glycosides, carbohydrates, lignans, iridoids, etc. The crude extracts and isolated compounds have exhibited a wide range of in vitro and in vivo pharmacologic effects, such as neuroprotective, immunomodulatory, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, and anti-tumor effects. The phenylethanoid glycosides, echinacoside and acteoside have attracted the most attention for their significantly neuropharmacology effects. Pharmacokinetic studies of echinacoside and acteoside also have also been summarized. Phenylethanoid glycosides have demonstrated wide pharmacological actions and have great clinical value if challenges such as poor bioavailability, fast and extensive metabolism are addressed. Apart from phenylethanoid glycosides, other constituents of Cistanches Herba, their

  18. The sedative effects and mechanism of action of cedrol inhalation with behavioral pharmacological evaluation.

    Science.gov (United States)

    Kagawa, Daiji; Jokura, Hiroko; Ochiai, Ryuji; Tokimitsu, Ichiro; Tsubone, Hirokazu

    2003-07-01

    It has been reported that cedarwood oil has sedative effects when inhaled. In this study, we evaluated sedative effects of inhaled cedrol, which is a major component of cedarwood oil. Accumulative spontaneous motor activity was significantly decreased in the cedrol-exposed Wistar rats. Similar results were confirmed in caffeine-treated Wistar rats, spontaneously hypertensive rats (SHR), and ddY mice. In addition, exposure to cedrol prolonged pentobarbital-induced sleeping time in Wistar rats. To investigate whether cedrol, which has a very faint aroma, affects the olfactory system, the nasal cavities of Wistar rats were treated with zinc sulfate to reduce olfactory function. Two days later, the pentobarbital-induced sleep time was measured as described above. Compared to intact rats, the sleep prolongation effect was decreased in a lavender-roman chamomile mixed oil exposure positive control group, indicating that olfactory function was impaired. In contrast, prolongation of the sleeping time did not change in the cedrol exposure group. The above findings indicate that cedrol inhalation had marked sedative effects regardless of the animal species or the functional state of the autonomic nerves, suggesting that the mechanism of action is via a pathway other than the olfactory system.

  19. Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, S H.M. [Durng Research Dept., National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)

    1995-10-01

    The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab.

  20. Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

    International Nuclear Information System (INIS)

    Hassan, S.H.M.

    1995-01-01

    The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab

  1. Beyond reverse pharmacology: Mechanism-based screening of Ayurvedic drugs.

    Science.gov (United States)

    Lele, R D

    2010-10-01

    This paper reviews the pharmacology of Indian medicinal plants, starting with the historical background of European work on the subject beginning as early as the 17th century, and tracing its history through the work of Sen and Bose in the 1930's, and Vakhil's historic 1949 paper on Sarpaghanda. The often crucial role of patient feedback in early discoveries is highlighted, as is the time lag between proof of pharmacological action and identification of the active principle, and subsequent elucidation of mechanism of action. In the case of Indian plants in the 20th century this process sometimes took almost 50 years. Reserpine and its mechanisms are given in detail, and its current relevance to public health discussed. The foundation of present day methods of pharmacology is briefly presented so the complexity of methods used to identify properties of Ayurveda derived drugs like forskolin and baicalein, and their bioavailability, may be better appreciated. Ayurveda derived anti-oxidants and their levels of action, immuno-modulators, particularly with respect to the NF-kB pathway and its implications for cancer control, are all considered. The example of curcumin derived from turmeric is explained in more detail, because of its role in cancer prevention. Finally, the paper emphasizes the importance of Ayurveda's concepts of rasayana as a form of dietary chemo-prevention; the significance of ahar, diet, in Ayurveda's aspiration to prevent disease and restore health thus becomes clear. Understood in this light, Ayurveda may transcend pharmacology as a treatment paradigm.

  2. Beyond reverse pharmacology: Mechanism-based screening of Ayurvedic drugs

    Directory of Open Access Journals (Sweden)

    R D Lele

    2010-01-01

    Full Text Available This paper reviews the pharmacology of Indian medicinal plants, starting with the historical background of European work on the subject beginning as early as the 17th century, and tracing its history through the work of Sen and Bose in the 1930′s, and Vakhil′s historic 1949 paper on Sarpaghanda. The often crucial role of patient feedback in early discoveries is highlighted, as is the time lag between proof of pharmacological action and identification of the active principle, and subsequent elucidation of mechanism of action. In the case of Indian plants in the 20th century this process sometimes took almost 50 years. Reserpine and its mechanisms are given in detail, and its current relevance to public health discussed. The foundation of present day methods of pharmacology is briefly presented so the complexity of methods used to identify properties of Ayurveda derived drugs like forskolin and baicalein, and their bioavailability, may be better appreciated. Ayurveda derived anti-oxidants and their levels of action, immuno-modulators, particularly with respect to the NF-kB pathway and its implications for cancer control, are all considered. The example of curcumin derived from turmeric is explained in more detail, because of its role in cancer prevention. Finally, the paper emphasizes the importance of Ayurveda′s concepts of rasayana as a form of dietary chemo-prevention; the significance of ahar, diet, in Ayurveda′s aspiration to prevent disease and restore health thus becomes clear. Understood in this light, Ayurveda may transcend pharmacology as a treatment paradigm.

  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.

    Science.gov (United States)

    Agaga, Luther Agbonyegbeni; John, Theresa Adebola

    2016-08-30

    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.

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

    Directory of Open Access Journals (Sweden)

    Zunting Pang

    2015-01-01

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

  5. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Mohamed Koriem

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Frederickson Martyn

    2010-01-01

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

  7. Cardiovascular Safety Pharmacology of Sibutramine.

    Science.gov (United States)

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

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Cecília Carboni Tardelli Cerveira

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

  9. Endothelial actions of atrial and B-type natriuretic peptides.

    Science.gov (United States)

    Kuhn, Michaela

    2012-05-01

    The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

  10. Breastfeeding information in pharmacology textbooks: a content analysis.

    Science.gov (United States)

    Amir, Lisa H; Raval, Manjri; Hussainy, Safeera Y

    2013-07-01

    Women often need to take medicines while breastfeeding and pharmacists need to provide accurate information in order to avoid undue caution about the compatibility of medicines and breastfeeding. The objective of this study was to review information provided about breastfeeding in commonly used pharmacology textbooks. We asked 15 Australian universities teaching pharmacy courses to provide a list of recommended pharmacology textbooks in 2011. Ten universities responded, generating a list of 11 textbooks that we analysed for content relating to breastfeeding. Pharmacology textbooks outline the mechanisms of actions of medicines and their use: however, only a small emphasis is placed on the safety/compatibility of medicines for women during breastfeeding. Current pharmacology textbooks recommended by Australian universities have significant gaps in their coverage of medicine use in breastfeeding. Authors of textbooks should address this gap, so academic staff can recommend texts with the best lactation content.

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

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. The pharmacology of lysergic acid diethylamide: a review.

    Science.gov (United States)

    Passie, Torsten; Halpern, John H; Stichtenoth, Dirk O; Emrich, Hinderk M; Hintzen, Annelie

    2008-01-01

    Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so-called "experimental psychosis" by altering neurotransmitter system and in psychotherapeutic procedures ("psycholytic" and "psychedelic" therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments. Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho-) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers. The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill.

  15. Recent Advances in Astragalus membranaceus Anti-Diabetic Research: Pharmacological Effects of Its Phytochemical Constituents

    Directory of Open Access Journals (Sweden)

    Kojo Agyemang

    2013-01-01

    Full Text Available The disease burden of diabetes mellitus is increasing throughout the world. The need for more potent drugs to complement the present anti-diabetic drugs has become an imperative. Astragalus membranaceus, a key component of most Chinese herbal anti-diabetic formulas, has been an important prospect for lead anti-diabetic compounds. It has been progressively studied for its anti-diabetic properties. Ethnopharmacological studies have established its potential to alleviate diabetes mellitus. Recent studies have sought to relate its chemical constituents to types 1 and 2 diabetes mellitus. Its total polysaccharides, saponins, and flavonoids fractions and several isolated compounds have been the most studied. The total polysaccharides fraction demonstrated activity to both types 1 and 2 diabetes mellitus. This paper discusses the anti-diabetic effects and pharmacological action of the chemical constituents in relation to types 1 and 2 diabetes mellitus.

  16. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Science.gov (United States)

    2010-04-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  18. Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery

    Science.gov (United States)

    Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.

    1993-04-01

    Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria.

    Science.gov (United States)

    Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina

    2016-03-01

    Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.

  1. Carotenoids: biochemistry, pharmacology and treatment.

    Science.gov (United States)

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

    2017-06-01

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

  2. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.

    Science.gov (United States)

    Faraone, Stephen V

    2018-04-01

    Psychostimulants, including amphetamines and methylphenidate, are first-line pharmacotherapies for individuals with attention-deficit/hyperactivity disorder (ADHD). This review aims to educate physicians regarding differences in pharmacology and mechanisms of action between amphetamine and methylphenidate, thus enhancing physician understanding of psychostimulants and their use in managing individuals with ADHD who may have comorbid psychiatric conditions. A systematic literature review of PubMed was conducted in April 2017, focusing on cellular- and brain system-level effects of amphetamine and methylphenidate. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2. There is also evidence for interactions with glutamate and opioid systems. Clinical implications of these actions in individuals with ADHD with comorbid depression, anxiety, substance use disorder, and sleep disturbances are discussed. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

  3. Pharmacology of midazolam.

    Science.gov (United States)

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

    1981-01-01

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

  4. The preclinical pharmacology of mephedrone; not just MDMA by another name.

    Science.gov (United States)

    Green, A R; King, M V; Shortall, S E; Fone, K C F

    2014-05-01

    The substituted β-keto amphetamine mephedrone (4-methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). This review critically examines the preclinical data on mephedrone that have appeared over the last 2-3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5-HT in the brain as shown by in vivo and in vitro studies. The effect on 5-HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5-HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones. © 2014 The British Pharmacological Society.

  5. Systems pharmacology for traditional Chinese medicine with application to cardio-cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Yingxue Fu

    2014-10-01

    Full Text Available Identified as a treasure of natural herbal products, traditional Chinese medicine (TCM has attracted extensive attention for their moderate treatment effect and lower side effect. Cardio-cerebrovascular diseases (CCVD are a leading cause of death. TCM is used in China to prevent and treat CCVD. However, the complexity of TCM poses challenges in understanding the mechanisms of herbs at a systems-level, thus hampering the modernization and globalization of TCM. A novel model, termed traditional Chinese medicine systems pharmacology (TCMSP analysis platform, which relies on the theory of systems pharmacology and integrates absorption, distribution, metabolism, excretion and toxicity (ADME/T evaluation, target prediction and network/pathway analysis, was proposed to address these problems. Here, we review the development of systems pharmacology, the TCMSP approach and its applications in the investigations of CCVD and compare it with other methods. TCMSP assists in uncovering the mechanisms of action of herbal formulas used in treating CCVD. It can also be applied in ascertaining the different syndrome patterns of coronary artery disease, decoding the multi-scale mechanisms of herbs, and in understanding the mechanisms of herbal synergism.

  6. Biochemical and pharmacological characterization of irradiated crotamine by gamma rays of 60Co

    International Nuclear Information System (INIS)

    Oliveira, Karina Corleto

    2014-01-01

    The serum production in Brazil, the only effective treatment in cases of snakebites, uses horses that although large size, have reduced l lifespan compared with horses not immunized. Ionizing radiation has been shown as an excellent tool in reducing the toxicity of venoms and toxins isolated, and promote the achievement of better immunogens for serum production, and contributing to the welfare of serum-producing animals. It is known, however, that the effects of ionizing radiation on protein are characterized by various chemical modifications, such as fragmentation, cross-linking due to aggregation and oxidation products generated by water radiolysis. However, the action of gamma radiation on toxins is not yet fully understood structurally and pharmacologically, a fact that prevents the application of this methodology in the serum production process. So we proposed in this paper the characterization of crotamine, an important protein from the venom of Crotalus durissus terrificus species, irradiated with 60 Co gamma rays. After isolating the toxin by chromatographic techniques and testing to prove the obtaining of pure crotamine, it was irradiated with gamma rays and subjected to structural analysis, Fluorescence and Circular Dichroism. Using high hydrostatic pressure tests were also conducted in order to verify that the conformational changes caused by radiation suffer modifications under high pressures. From the pharmacological point of view, muscle contraction tests were conducted with the objective of limiting the action of crotamine in smooth muscle as well as the change in the action of toxin caused structural changes to the front. Analysis of Circular Dichroism and Fluorescence showed changes in structural conformation of crotamine when subjected to gamma radiation and that such changes possibly occurring in the secondary and tertiary structure of the protein. The observed in pharmacological tests showed that the irradiated crotamine was less effective in

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Network-based Approaches in Pharmacology.

    Science.gov (United States)

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

    2017-10-01

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

  9. 2-Aminothiophene scaffolds: Diverse biological and pharmacological attributes in medicinal chemistry.

    Science.gov (United States)

    Bozorov, Khurshed; Nie, Li Fei; Zhao, Jiangyu; Aisa, Haji A

    2017-11-10

    2-Aminothiophenes are important five-membered heterocyclic building blocks in organic synthesis, and the chemistry of these small molecules is still developing based on the discovery of cyclization by Gewald. Another attractive feature of 2-aminothiophene scaffolds is their ability to act as synthons for the synthesis of biological active thiophene-containing heterocycles, conjugates and hybrids. Currently, the biological actions of 2-aminothiophenes or their 2-N-substituted analogues are still being investigated because of their various mechanisms of action (e.g., pharmacophore and pharmacokinetic properties). Likewise, the 2-aminothiophene family is used as diverse promising selective inhibitors, receptors, and modulators in medicinal chemistry, and these compounds even exhibit effective pharmacological properties in the various clinical phases of appropriate diseases. In this review, major biological and pharmacological reports on 2-aminothiophenes and related compounds have been highlighted; most perspective drug-candidate hits were selected for discussion and described, along with additional synthetic pathways. In addition, we focused on the literature dedicated to 2-aminothiophenes and 2-N-substituted derivatives, which have been published from 2010 to 2017. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Science.gov (United States)

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. PHARMACOLOGICAL AND MEDICINAL CHEMISTRY ASPECTS OF CANNABIS COMPOUNDS

    Directory of Open Access Journals (Sweden)

    T. Cotelea

    2011-12-01

    Full Text Available The current communication includes a general overview of the scientific interest and medicianl chemistry aspects of Cannabis compounds. It relates to metabolism, pharmacological action and phisico-chemical analysis of these compounds, as well as of some isomers differing in spatial arrangement of functional groups.

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

    OpenAIRE

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

    2017-01-01

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

  13. Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); D.M. Oosterveer (Daniella); G. Brufau (Gemma); M. Boesjes (Marije); F. Kuipers (Folkert); A. Groen (Albert)

    2012-01-01

    textabstractObjective: Pharmacological LXR activation has anti-atherosclerotic actions in animal models. Part of these beneficial effects may be explained by accelerated reverse cholesterol transport since both plasma high density lipoprotein (HDL) cholesterol and fecal neutral sterol secretion are

  14. The use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

    Science.gov (United States)

    Moll, Jennifer L; Brown, Candace S

    2011-04-01

    The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective

  15. Effects of dietary biotin supplementation on glucagon production, secretion, and action.

    Science.gov (United States)

    Lazo-de-la-Vega-Monroy, Maria-Luisa; Larrieta, Elena; Tixi-Verdugo, Wilma; Ramírez-Mondragón, Rafael; Hernández-Araiza, Ileana; German, Michael S; Fernandez-Mejia, Cristina

    Despite increasing evidence that pharmacologic concentrations of biotin modify glucose metabolism, to our knowledge there have not been any studies addressing the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. The aim of this study was to investigate the effects of dietary biotin supplementation on glucagon expression, secretion, and action. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 wk postweaning. Glucagon gene mRNA expression was measured by the real-time polymerase chain reaction. Glucagon secretion was assessed in isolated islets and by glucagon concentration in plasma. Glucagon action was evaluated by glucagon tolerance tests, phosphoenolpyruvate carboxykinase (Pck1) mRNA expression, and glycogen degradation. Compared with the control group, glucagon mRNA and secretion were increased from the islets of the biotin-supplemented group. Fasting plasma glucagon levels were higher, but no differences between the groups were observed in nonfasting glucagon levels. Despite the elevated fasting glucagon levels, no differences were found in fasting blood glucose concentrations, fasting/fasting-refeeding glucagon tolerance tests, glycogen content and degradation, or mRNA expression of the hepatic gluconeogenic rate-limiting enzyme, Pck1. These results demonstrated that dietary biotin supplementation increased glucagon expression and secretion without affecting fasting blood glucose concentrations or glucagon tolerance and provided new insights into the effect of biotin supplementation on glucagon production and action. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

    NARCIS (Netherlands)

    Grefhorst, Aldo; Oosterveer, Maaike H.; Brufau, Gemma; Boesjes, Marije; Kuipers, Folkert; Groen, Albert K.

    Objective: Pharmacological LXR activation has anti-atherosclerotic actions in animal models. Part of these beneficial effects may be explained by accelerated reverse cholesterol transport since both plasma high density lipoprotein (HDL) cholesterol and fecal neutral sterol secretion are higher upon

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

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

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

  18. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2014-01-01

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

  19. Effective action and brane running

    International Nuclear Information System (INIS)

    Brevik, Iver; Ghoroku, Kazuo; Yahiro, Masanobu

    2004-01-01

    We address the renormalized effective action for a Randall-Sundrum brane running in 5D bulk space. The running behavior of the brane action is obtained by shifting the brane position without changing the background and fluctuations. After an appropriate renormalization, we obtain an effective, low energy brane world action, in which the effective 4D Planck mass is independent of the running position. We address some implications for this effective action

  20. The pharmacologic and clinical effects of medical cannabis.

    Science.gov (United States)

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

    2013-02-01

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

  1. Complement-induced histamine release from human basophils. III. Effect of pharmacologic agents.

    Science.gov (United States)

    Hook, W A; Siraganian, R P

    1977-02-01

    Human serum activated with zymosan generates a factor (C5a) that releases histamine from autologous basophils. Previously we have presented evidence that this mechanism for C5a-induced release differs from IgE-mediated reactions. The effect of several pharmacologic agents known to alter IgE-mediated release was studied to determine whether they have a similar action on serum-induced release. Deuterium oxide (D2O), which enhances allergic release, inhibited in a concentration-dependent fashion the serum-induced reaction at incubation temperatures of 25 and 32 degrees C. The colchicine-induced inhibition was not reversed by D2O. Cytochalasin B, which gives a variable enhancement of IgE-mediated release, had a marked enhancing effect on the serum-induced reaction in all subjects tested. The following agents known to inhibit the IgE-mediated reaction also inhibited serum-induced release at 25 degrees C: colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine, and 2-deoxy-D-glucose. These results suggest that the serum-induced release is modulated by intracellular cyclic AMP, requires energy, and is enhanced by the disruption of microfilaments. The lack of an effect by D2O would suggest that microtubular stabilization is not required. The data can be interpreted to indicate that IgE- and C5a-mediated reactions diverge at a late stage in the histamine release pathway.

  2. New concepts in antimalarial use and mode of action in dermatology.

    Science.gov (United States)

    Kalia, Sunil; Dutz, Jan P

    2007-01-01

    Although chloroquine, hydroxychloroquine and quinacrine were originally developed for the treatment of malaria, these medications have been used to treat skin disease for over 50 years. Recent clinical data have confirmed the usefulness of these medications for the treatment of lupus erythematosus. Current research has further enhanced our understanding of the pharmacologic mechanisms of action of these drugs involving inhibition of endosomal toll-like receptor (TLR) signaling limiting B cell and dendritic cell activation. With this understanding, the use of these medications in dermatology is broadening. This article highlights the different antimalarials used within dermatology through their pharmacologic properties and mechanism of action, as well as indicating their clinical uses. In addition, contraindications, adverse effects, and possible drug interactions of antimalarials are reviewed.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Pharmacological and therapeutic directions in ADHD: Specificity in the PFC

    Directory of Open Access Journals (Sweden)

    Levy Florence

    2008-02-01

    Full Text Available Abstract Background Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. Hypothesis The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA stimulation (through DAT transporter inhibition decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC, and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance

  5. Potential functional and pathological side effects related to off-target pharmacological activity.

    Science.gov (United States)

    Lynch, James J; Van Vleet, Terry R; Mittelstadt, Scott W; Blomme, Eric A G

    2017-09-01

    Most pharmaceutical companies test their discovery-stage proprietary molecules in a battery of in vitro pharmacology assays to try to determine off-target interactions. During all phases of drug discovery and development, various questions arise regarding potential side effects associated with such off-target pharmacological activity. Here we present a scientific literature curation effort undertaken to determine and summarize the most likely functional and pathological outcomes associated with interactions at 70 receptors, enzymes, ion channels and transporters with established links to adverse effects. To that end, the scientific literature was reviewed using an on-line database, and the most commonly reported effects were summarized in tabular format. The resultant table should serve as a practical guide for research scientists and clinical investigators for the prediction and interpretation of adverse side effects associated with molecules interacting with components of this screening battery. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The study of chemical composition and pharmacological action of the alkaloid from plants of Lycoris Herb

    Science.gov (United States)

    Ji, Y. B.; Wei, C.; Xin, G. S.

    2017-12-01

    Recently, studies on Lycoris type alkaloids received the attention of scholars home and abroad. Lycoris type contains lots of alkaloids, it can be divided into seven types according to its molecular structure, including Lycorine, Crinine, Galanthamine, Tazettine, Narciclasine, Lycorenine, Homolycorine and Montanine. Researches have shown that Lycoris type possess multiple phamocology activity, such as strong anti-tumor activity of human breast cancer cell (MCF-7), human leukemia cell(HL-60); and strong inhibition effect of flu virus, measles virus, polio virus and SARS virus; Besides, Lycorine type has strong anti-Acetylcholinesterase effect. In a word, Lycorine type, Lycoris type alkaloids carries multiple pharmacology effect and is a promising substance.

  7. PHARMACOLOGICAL EFFECTS AND THERAPEUTIC PROPERTIES OF HIBISCUS CANNABINUS- A REVIEW

    OpenAIRE

    Ali Esmail Al-Snafi

    2018-01-01

    The phytochemical analysis of Hibiscus cannabinus showed the presence of phytosterols, flavonoids, polyphenols, tannins, steroids, alkaloids, saponins, lignans, essential oils, glucosides such as cannabiscitrin, cannabiscetin and anthocyanin glycoside. The pharmacological studies revealed that Hibiscus cannabinus possessed cytotoxic, anthelmintic, antibacterial, antiulcer, antidiabetic, hypolipidemic, antioxidant, immunological, haematinic and hepatoprotective effects. This review will highli...

  8. Pharmacological cardioversion of atrial fibrillation with vernakalant: evidence in support of the ESC Guidelines.

    Science.gov (United States)

    Savelieva, Irene; Graydon, Richard; Camm, A John

    2014-02-01

    Pharmacological rhythm control (often including electrical or pharmacological cardioversion) is an integral part of therapy for atrial fibrillation (AF) worldwide. Antiarrhythmic drug strategies would be preferred in many patients provided effective and safe antiarrhythmic agents are available. Also, pharmacological cardioversion could be the preferred option if the limitations of currently available drugs, such as restriction to patients without structural heart disease (flecainide and propafenone), risk of torsade de pointes (ibutilide), and slow onset of action (amiodarone), were overcome. The intravenous formulation of vernakalant (Brinavess, Cardiome) has been approved for pharmacological cardioversion of recent-onset AF (≤7 days) and early (≤3 days) post-operative AF in the European Union, Iceland, and Norway. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and has minimal effects in the ventricles and thus, is thought to have a low proarrhythmic potential. Vernakalant is administered as a 10 min infusion of 3 mg/kg, and if AF persists after 15 min, an additional dose of 2 mg/kg can be given. The efficacy and safety of the drug has been extensively investigated in randomized controlled trials against placebo and an active comparator (amiodarone). The placebo-extracted efficacy of vernakalant is ∼47%. A significant advantage is a rapid effect, with the median to conversion ranging between 8 and 14 min, with the majority of patients (75-82%) converting after the first dose. Vernakalant retained its efficacy in subgroups of patients with associated cardiovascular disease such as hypertension and ischaemic heart disease, but its benefit may be lower and risk of adverse effects is higher in patients with heart failure. In the post-market reports, cardioversion rates with vernakalant are 65-70%. This review focuses on the role of vernakalant in pharmacological cardioversion for AF.

  9. Lipid Peroxidation: Pathophysiology and Pharmacological Implications in the Eye

    Directory of Open Access Journals (Sweden)

    Ya Fatou eNjie-Mbye

    2013-12-01

    Full Text Available Oxygen-derived free radicals such as hydroxyl and hydroperoxyl species have been shown to oxidize phospholipids and other membrane lipid components leading to lipid peroxidation. In the eye, lipid peroxidation has been reported to play an important role in degenerative ocular diseases (age-related macular degeneration, cataract, glaucoma, diabetic retinopathy. Indeed, ocular tissues are prone to damage from reactive oxygen species due to stress from constant exposure of the eye to sunlight, atmospheric oxygen and environmental chemicals. Furthermore, free radical catalyzed peroxidation of long chain polyunsaturated acids (LCPUFAs such as arachidonic acid and docosahexaenoic acid leads to generation of LCPUFA metabolites including isoprostanes and neuroprostanes that may further exert pharmacological/toxicological actions in ocular tissues. Evidence from literature supports the presence of endogenous defense mechanisms against reactive oxygen species in the eye, thereby presenting new avenues for the prevention and treatment of ocular degeneration. Hydrogen peroxide (H2O2 and synthetic peroxides can exert pharmacological and toxicological effects on tissues of the anterior uvea of several mammalian species. There is evidence suggesting that the retina, especially retinal ganglion cells can exhibit unique characteristics of antioxidant defense mechanisms. In the posterior segment of the eye, H2O2 and synthetic peroxides produce an inhibitory action on glutamate release (using [3H]-D-aspartate as a marker, in vitro and on the endogenous glutamate and glycine concentrations in vivo. In addition to peroxides, isoprostanes can elicit both excitatory and inhibitory effects on norepinephrine (NE release from sympathetic nerves in isolated mammalian iris ciliary bodies. Whereas isoprostanes attenuate dopamine release from mammalian neural retina, in vitro, these novel arachidonic acid metabolites exhibit a biphasic regulatory effect on glutamate release

  10. The effect of pharmacological treatment on gait biomechanics in peripheral arterial disease patients

    Science.gov (United States)

    2010-01-01

    Background Pharmacological treatment has been advocated as a first line therapy for Peripheral Arterial Disease (PAD) patients suffering from intermittent claudication. Previous studies document the ability of pharmacological treatment to increase walking distances. However, the effect of pharmacological treatment on gait biomechanics in PAD patients has not been objectively evaluated as is common with other gait abnormalities. Methods Sixteen patients were prescribed an FDA approved drug (Pentoxifylline or Cilostazol) for the treatment of symptomatic PAD. Patients underwent baseline gait testing prior to medication use which consisted of acquisition of ground reaction forces and kinematics while walking in a pain free state. After three months of treatment, patients underwent repeat gait testing. Results Patients with symptomatic PAD had significant gait abnormalities at baseline during pain free walking as compared to healthy controls. However, pharmacological treatment did not produce any identifiable alterations on the biomechanics of gait of the PAD patients as revealed by the statistical comparisons performed between pre and post-treatment and between post-treatment and the healthy controls. Conclusions Pharmacological treatment did not result in statistically significant improvements in the gait biomechanics of patients with symptomatic PAD. Future studies will need to further explore different cohorts of patients that have shown to improve significantly their claudication distances and/or their muscle fiber morphology with the use of pharmacological treatment and determine if this is associated with an improvement in gait biomechanics. Using these methods we may distinguish the patients who benefit from pharmacotherapy and those who do not. PMID:20529284

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

    Directory of Open Access Journals (Sweden)

    Crippa José AS

    2012-01-01

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

  12. Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

    Science.gov (United States)

    Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

    2018-02-01

    Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, pLearning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2018-06-01

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

  14. Antioxidant effects of carotenoids

    NARCIS (Netherlands)

    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

  15. [History and pharmacology of trazodone].

    Science.gov (United States)

    Agnoli, A

    1986-10-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Current trends and future development in pharmacologic stress testing

    International Nuclear Information System (INIS)

    Bae, Jin Ho; Lee, Jae Tae

    2005-01-01

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

  18. Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review.

    Science.gov (United States)

    Guo, Rixin; Wang, Ting; Zhou, Guohong; Xu, Mengying; Yu, Xiankuo; Zhang, Xiao; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

    2018-01-01

    Strychnos nux-vomica L. belongs to the genus Strychnos of the family Loganiaceae and grows in Sri Lanka, India and Australia. The traditional medicinal component is its seed, called Nux vomica. This study provides a relevant and comprehensive review of S. nux-vomica L., including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology, thus providing a foundation for future studies. Up to the present day, over 84 compounds, including alkaloids, iridoid glycosides, flavonoid glycosides, triterpenoids, steroids and organic acids, among others, have been isolated and identified from S. nux-vomica. These compounds possess an array of biological activities, including effects on the nervous system, analgesic and anti-inflammatory actions, antitumor effects, inhibition of the growth of pathogenic microorganisms and regulation of immune function. Furthermore, toxicity and detoxification methods are preliminarily discussed toward the end of this review. In further research on S. nux-vomica, bioactivity-guided isolation strategies should be emphasized. Its antitumor effects should be investigated further and in vivo animal experiments should be performed alongside in vitro testing. The pharmacological activity and toxicology of strychnine [Formula: see text]-oxide and brucine [Formula: see text]-oxide should be studied to explore the detoxification mechanism associated with processing more deeply.

  19. Low prevalence of hypertension with pharmacological treatments and associated factors

    Directory of Open Access Journals (Sweden)

    Helena Gama

    2013-06-01

    Full Text Available OBJECTIVE: To assess the determinants of the lack of pharmacological treatment for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were evaluated. Blood pressure, weight, height and smoking status were assessed following the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Hypertensives (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive drug therapy were evaluated for awareness of their condition, pharmacological and non-pharmacological management, as well as use of herbal or traditional remedies. Prevalence ratios (PR were calculated, adjusted for sociodemographic characteristics, cardiovascular risk factors and non-pharmacological treatment. RESULTS: Most of the hypertensive subjects (92.3%, and nearly half of those aware of their condition were not treated pharmacologically. Among the aware, the prevalence of untreated hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI 1.10;2.36} and was lower in subjects under non-pharmacological treatment (PR = 0.58; 95%CI 0.42;0.79; there was no significant association with traditional treatments (PR = 0.75; 95%CI 0.44;1.26. CONCLUSIONS: The lack of pharmacological treatment for hypertension was more frequent in men, and was not influenced by the presence of other cardiovascular risk factors; it could not be explained by the use of alternative treatments as herbal/traditional medicines or non-pharmacological management. It is important to understand the reasons behind the lack of management of diagnosed hypertension and to implement appropriate corrective actions to reduce the gap in the access to healthcare between developed and developing countries.

  20. Molecular actions and clinical pharmacogenetics of lithium therapy

    Science.gov (United States)

    Can, Adem; Schulze, Thomas G.; Gould, Todd D.

    2014-01-01

    Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future. PMID:24534415

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

    Science.gov (United States)

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

    2018-06-12

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

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

    Directory of Open Access Journals (Sweden)

    von Wolff Alessa

    2010-11-01

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

  3. Wilsonian effective action of superstring theory

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Ashoke [Harish-Chandra Research Institute,Chhatnag Road, Jhusi, Allahabad 211019 (India); Homi Bhabha National Institute,Training School Complex, Anushakti Nagar, Mumbai 400085 (India)

    2017-01-25

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

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

    Science.gov (United States)

    Gu, Hao; Zhang, Yan-Ling; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    Medicinal properties are the basic attribute of traditional Chinese medicines (TCM), while the medicinal property theory is the core theoretical foundation of TCM formula combination. In this particle, authors studied the characteristics of pharmacological effects of property combination of traditional Chinese medicines distributing along meridians, with the aim to introduce the medicinal property combination regularity into the design and optimization process of compound TCMs, and bring the medicinal property theory into full play in guiding the formula combination. In this paper, TCMs distributing along "the lung meridian" was taken for example. The medicinal property combinations of TCMs distributing along "the lung meridian" recorded in Pharmacopeia (2010) was collected and processed. Besides, Chinese journal full-text database (CNKI) was used to collect all of pharmacological study literatures concerning the above TCMs that have been published since 1980. The pharmacological information was also supplemented by reference to Science of Chinese Materia Medica and Clinical Science of Chinese Materia Medica. TCMs distributing along the lung meridian with different properties and tastes showed significant differences in pharmacological effects. For example, mild-sweet-lung medicines could lower blood sugar levels, decrease anoxia and enhance immunity; Mild-bitter-lung medicines showed anti-bacterial, anti-hypertension, anti-oxidation effects; Hot-sweet-lung medicines showed antibechic and anti-bacterial effects. And Hot-bitter-lung medicines showed phlegm eliminating and anti-inflammatory effects. Meanwhile, TCMs distributing along the lung meridian had similar pharmacological characteristics, such as anti-bacterial and anti-inflammatory effects, which is consistent with lung's feature in susceptibility to exogenous pathogenic factors. In this study, authors discovered pharmacological characteristics of different TCMs distributing along the lung meridian, which

  5. Effect of lipopolysaccharide on inflammation and insulin action in human muscle.

    Science.gov (United States)

    Liang, Hanyu; Hussey, Sophie E; Sanchez-Avila, Alicia; Tantiwong, Puntip; Musi, Nicolas

    2013-01-01

    Accumulating evidence from animal studies suggest that chronic elevation of circulating intestinal-generated lipopolysaccharide (LPS) (i.e., metabolic endotoxemia) could play a role in the pathogenesis of insulin resistance. However, the effect of LPS in human muscle is unclear. Moreover, it is unknown whether blockade/down regulation of toll-like receptor (TLR)4 can prevent the effect of LPS on insulin action and glucose metabolism in human muscle cells. In the present study we compared plasma LPS concentration in insulin resistant [obese non-diabetic and obese type 2 diabetic (T2DM)] subjects versus lean individuals. In addition, we employed a primary human skeletal muscle cell culture system to investigate the effect of LPS on glucose metabolism and whether these effects are mediated via TLR4. Obese non-diabetic and T2DM subjects had significantly elevated plasma LPS and LPS binding protein (LBP) concentrations. Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals.

  6. Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness.

    Science.gov (United States)

    Hamill, Jonathan; Hallak, Jaime; Dursun, Serdar M; Baker, Glen

    2018-01-24

    Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience. More recently it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation. To review ayahuasca's behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness. We searched Medline, in English, using the terms ayahuasca, dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications. The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects, safety and adverse effects; pharmacology; potential psychiatric uses. Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and many present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers feel that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized credible researchers to conduct comprehensive clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Pharmacologic treatment of depression in multiple sclerosis

    NARCIS (Netherlands)

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

    2011-01-01

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

  8. Kampo medicine: Evaluation of the pharmacological activity of 121 herbal drugs on GABA(A and 5 HT3A receptors

    Directory of Open Access Journals (Sweden)

    Katrin M Hoffmann

    2016-07-01

    Full Text Available Kampo medicine is a form of Japanese phytotherapy originating from traditional Chinese medicine (TCM. During the last several decades, much attention has been paid to the pharmacological effects of these medical plants and its constituents. However, in many cases, a systematic screening of Kampo remedies to determine pharmacologically relevant targets is still lacking. In this study, we performed a broad screening of Kampo remedies to look for pharmacologically relevant 5 HT3A and GABA(A receptor ligands. Several of the Kampo remedies are currently used for symptoms such as nausea, emesis, gastrointestinal motility disorders, anxiety, restlessness or insomnia. Therefore, we analyzed the pharmacological effects of 121 herbal drugs from Kampo medicine as ethanol tinctures on heterologously expressed 5 HT3A and GABA(A receptors, due to the involvement of these receptors in such pathophysiological processes. The tinctures of Lindera aggregata (radix and Leonurus japonicus (herba were the most effective inhibitory compounds on the 5 HT3A receptor. Further investigation of known ingredients in these compounds led to the identification of leonurine from Leonurus as a new natural 5 HT3A receptor antagonist. We also identified several potentiating herbs (e.g., Magnolia officinalis (cortex, Syzygium aromaticum (flos and Panax ginseng (radix for the GABAA receptor, which are all traditionally used for their sedative or anxiolytic effects. A variety of tinctures with antagonistic effects, for instance Salvia miltiorrhiza (radix were also detected. Therefore, this study reveals new insights into the pharmacological action of a broad spectrum of herbal drugs from Kampo, allowing a better understanding of their physiological effects and clinical applications.

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

    Science.gov (United States)

    Taverner, Tarnia

    2015-08-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

  11. A Review of Botany and Pharmacological Effect and Chemical Composition of Echinophora Species Growing in Iran.

    Science.gov (United States)

    Hosseini, Zohreh; Lorigooini, Zahra; Rafieian-Kopaei, Mahmoud; Shirmardi, Hamzeh Ali; Solati, Kamal

    2017-01-01

    This review was conducted to investigate the botany, phytochemistry, and pharmacological properties of Echinophora species. The information of this review was obtained by searching for keywords Apiaceae , Echinophora , pharmacological effects, and traditional and modern medicine in scientific articles and books published in search engines Scopus, Google Scholar, Science Direct, PubMed, and Web of Science. The traditional uses of Echinophora and the existence of valuable phytochemicals in the plant have led to isolation and drug discovery of natural medicines such as antibiotic, analgesics, and anticancer drugs, and the beneficial effects of these plants can widely be used in healthcare. Echinophora species are medicinal and aromatic plants that are belong to Apiaceae family. This genus have four species in Iran. The botany, geographical distribution, traditional and pharmacological effects of Echinophora genus were described. Also, the major chemical constituents of the essential oil and extract of different species of Echinophora that have been reported. Overall, the existence of valuable phytochemicals purpose Echinophora species as novel candidate to isolation and drug discovery of natural medicines such as antibiotic, analgesics, and anticancer drugs.

  12. Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

    Science.gov (United States)

    Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

    2015-03-01

    DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

  13. The relationship between impulsive choice and impulsive action: a cross-species translational study.

    Directory of Open Access Journals (Sweden)

    Nienke Broos

    Full Text Available Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task and impulsive action (five-choice serial reaction time task paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT and impulsive action (immediate and delayed memory task, IMT/DMT. Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action and filled out the Barratt impulsiveness scale (BIS-11. Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1 self-reported impulsivity (BIS-11; (2 impulsive action (IMT/DMT and SST; (3 impulsive choice (DDT. This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.

  14. Pharmacological Studies of p, N-(3, 4-Methylenedioxy phenyl Benzoic Acid (RRL-1364 - Part-I

    Directory of Open Access Journals (Sweden)

    Dahanukar Sharadini

    1978-01-01

    Full Text Available Detailed pharmacological investigations of p-N-(3, 4-methylene dioxy phenyl benzoic acid revealed marked hypotensive action which was dose dependent and most marked in cats; it was absent in rats. Atropine could block this hypotensive action, thus suggest-ing cholinomimetic mechanism. Further studies indicated that the hypotension produced was central and possibly medullary in origin.

  15. Synthesis and preliminary pharmacological evaluation of asymmetric chloroquine analogues.

    Science.gov (United States)

    Witiak, D T; Grattan, D A; Heaslip, R J; Rahwan, R G

    1981-06-01

    Asymmetric chloroquine analogues (1-4) were prepared of known absolute configuration in order to assess stereochemical influences on selected biological activities. Since chloroquine has been shown to possess spasmolytic properties, analogues 1-4 were tested for similar pharmacological effects on smooth-muscle contraction. The (S)- and (R)-chlorochloroquine enantiomers (1 and 2, respectively) were more potent antispasmodics than the less lipophilic (S)- and (R)-hydroxychloroquines (3 and 4, respectively) when tested against KCl- or acetylcholine-induced contractions of the isolated mouse ileum. A membrane stabilizing mechanism of action for the chloroquine analogues is proposed since neither cellular toxicity nor calcium antagonism plays a role in the spasmolytic action of these compounds. Although compounds 1-4 also inhibited PGF2 alpha-induced contractions of the ileum, 1 was significantly more potent than 2; the latter in turn was equipotent to 3 and 4. It is tentatively proposed that 1 may possess stereoselective affinity for the PGF2 alpha receptor in the ileum. This observation may be further exploited to obtain more selective profiles of biological activity through molecular manipulation.

  16. The chemistry and pharmacology of Ligularia przewalskii: A review.

    Science.gov (United States)

    Liu, Shi-Jun; Tang, Zhi-Shu; Liao, Zhi-Xin; Cui, Chun-Li; Liu, Hong-Bo; Liang, Yan-Ni; Zhang, Yu; Xu, Hong-Bo; Zhang, Dong-Bo; Zheng, Ya-Ting; Shi, Huan-Xian; Li, Shi-Ying

    2018-06-12

    hepatotoxicity. The lung-moistening, cough-relieving and phlegm-resolving actions of the root of LP are attributed to the anti-inflammatory properties of flavonoids and terpenoids. The heat-clearing, dampness-removing and gallbladder-normalizing (to cure jaundice) actions of the flowers of LP are based on the anti-inflammatory, antioxidant and hepatoprotective activity properties of terpenoids, flavonoids and sterols. The Traditional Chinese Medicine (TCM) characteristics of LP (bitter flavour) corroborate its potent anti-inflammatory effects. In addition, the remarkable anti-inflammatory and antioxidant capacities of LP contribute to its anti-tumour and antitussive activities. Many conventional uses of LP have now been validated by modernized pharmacological research. For future research, further phytochemical and biological studies need to be conducted on LP, In particular, the safety, mechanism of action and efficacy of LP could be of future research interest before beginning clinical trials. More in vivo experiments and clinical studies are encouraged to further clarify the relation between traditional uses and modern applications. Regarding the roots, leaves and flowers of LP, their chemical compositions and clinical effects should be compared. The information on LP will be helpful in providing and identifying its therapeutic potential and economic value for its use as a new medicine in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Isotope effects: definitions and consequences for pharmacologic studies

    International Nuclear Information System (INIS)

    Van Langenhove, A.

    1986-01-01

    The use of stable isotope-labeled compounds for pharmacologic studies requires careful consideration of the nature of the stable isotope label (2H, 13C, 15N, 18O) and its position of incorporation in the molecule. When deuterium is used, improper positioning can lead to significant primary isotope effects. Primary isotope effects occur when the breaking of the bond to the heavy isotope is the rate-limiting step in a reaction (or metabolic transformation). A reaction will proceed slower for the molecule with the heavy isotope label because of the mass difference between the light and the heavy isotope. In addition to these primary isotope effects, smaller but nevertheless important secondary isotope effects, physicochemical isotope effects, active hydrogen/deuterium exchange, or isotope effects associated with either the enzyme-catalyzed biotransformation or the mass spectrometric ionization and fragmentation can be operative. In mechanistic studies, isotope effects are used to their advantage; however, in pharmacokinetic studies, the occurrence of isotope effects can lead to grossly misleading biologic and analytic results: the metabolism of the drug will differ when in vivo isotope effects are operative, and isotope effects occurring during the analysis procedure will obscure the true metabolic profile of the drug

  18. Hemodynamic effects of a novel pharmacologic stress agent, Higemine

    International Nuclear Information System (INIS)

    Zhang, X.L.; Liu, X.J.; Tao, Z.H.; Shi, R.F.

    2002-01-01

    Objective: Higenamine (dl-demethylcodaurine) (HG), which was isolated from aconitum japonicum. This study was to evaluate the hemodynamic effects of HG in animal study. Methods: We compared the hemodynamic effects of HG (0.5-4μg/min/kg) with Dobutamine (Dob) (5-30μg/min/kg) in 6 dogs: heart rate (HR), blood pressure (BP), coronary blood flow (CBF), myocardial oxygen consumption (MOC) were measured. Tolerability and safety of HG (1-500μg/mg/min) were evaluated in 8 dogs. Results: Comparison of hemodynamic effects between Dob an HG was presented. SBP: systolic blood pressure; DP: diastolic blood pressure; P<0.01; P<0.05. Diastolic BP slightly decreased, but systolic BP did not change significantly during HG infusion. There was no significant ECG abnormalities and side effects during HG infusion. Conclusion: HG might be a safe and useful pharmacologic stress agent, especially for patients with severe hypertension

  19. Reappraisal of GIP Pharmacology for Metabolic Diseases

    DEFF Research Database (Denmark)

    Finan, Brian; Müller, Timo D; Clemmensen, Christoffer

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....

  20. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Directory of Open Access Journals (Sweden)

    Yan M

    2015-10-01

    Full Text Available Meng Yan,1 Kaiping Zhang,1 Yanhui Shi,1 Lifang Feng,1 Lin Lv,1 Baoxin Li1,2 1Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China Abstract: Berberine (BBR, an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293 cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652 and phenylalanine (Phe656 in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. Keywords: berberine, hERG, cavoline-1, cardiotoxicity, LQTS, pharmacological rescue

  1. Differential, but not opponent, effects of L -DOPA and citalopram on action learning with reward and punishment.

    Science.gov (United States)

    Guitart-Masip, Marc; Economides, Marcos; Huys, Quentin J M; Frank, Michael J; Chowdhury, Rumana; Duzel, Emrah; Dayan, Peter; Dolan, Raymond J

    2014-03-01

    Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. To investigate the role of dopamine and serotonin in the interaction between action and valence during learning.Methods We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. We found that, after administration of levodopa,action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control.Citalopram had distinct effects, increasing participants'tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.

  2. Non-pharmacological modulation of cerebral white matter organization

    DEFF Research Database (Denmark)

    Kristensen, Tina D; Mandl, Rene C W; Jepsen, Jens R M

    2018-01-01

    OBJECTIVE: Neuroplasticity is a well-described phenomenon, but effects of non-pharmacological interventions on white matter (WM) are unclear. Here we review associations between active non-pharmacological interventions and WM organization in healthy subjects and in psychiatric patients. METHOD...

  3. Clozapine-resistant schizophrenia – non pharmacological augmentation methods

    Directory of Open Access Journals (Sweden)

    Gałaszkiewicz Joanna

    2017-12-01

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

  4. Influence of verbal instructions on effect-based action control.

    Science.gov (United States)

    Eder, Andreas B; Dignath, David

    2017-03-01

    According to ideomotor theory, people use bidirectional associations between movements and their effects for action selection and initiation. Our experiments examined how verbal instructions of action effects influence response selection without prior experience of action effects in a separate acquisition phase. Instructions for different groups of participants specified whether they should ignore, attend, learn, or intentionally produce acoustic effects produced by button presses. Results showed that explicit instructions of action-effect relations trigger effect-congruent action tendencies in the first trials following the instruction; in contrast, no evidence for effect-based action control was observed in these trials when instructions were to ignore or to attend to the action effects. These findings show that action-effect knowledge acquired through verbal instruction and direct experience is similarly effective for effect-based action control as long as the relation between the movement and the effect is clearly spelled out in the instruction.

  5. Ethnobotany, phytochemistry, toxicology and pharmacological properties of Terminalia sericea Burch. ex DC. (Combretaceae) - A review.

    Science.gov (United States)

    Mongalo, N I; McGaw, L J; Segapelo, T V; Finnie, J F; Van Staden, J

    2016-12-24

    The use of medicinal plants in the treatment of infections is ancient. A wide variety of ethnotherapeutic properties and pharmacological actions has been attributed to Terminalia sericea. Studies by various groups of investigators reveal that it is a multipurpose medicinal plant used mostly in the treatment of diarrhoea, sexually transmitted infections, skin rashes, tuberculosis and other infections. The current paper is aimed at providing an overview of the ethnomedicinal uses, toxicology, pharmacology and the phytochemistry of Terminalia sericea. Information was retrieved using various search engines, including Pubmed, Science Direct, Google Scholar, Scielo, SciFinder and Scopus. The key words used included Terminalia sericea, secondary metabolites, phytochemistry, biological activity, pharmacology, ethnobotanical survey, medicinal uses, safety, toxicology and other related words. Terminalia sericea is an important medicinal plant which possesses anti-HIV, anti-fungal, anti-bacterial, anticancer, lipolytic, wound healing, antiparasitic, anti-inflammatory and anti-oxidant activity, as the most valuable biological activities, thus lending pharmacological support to the plant's folkloric uses in indigenous medicine. Toxicologically, the extracts and isolated compounds from the plant species may have mild toxic effects. Phytochemically, the plant species possesses valuable compounds including triterpenes, alkaloids and flavonoids which may well contribute to its biological activity. Terminalia sericea contains secondary metabolites which are valuable in the treatment of a variety of human infections, including community acquired infections which may be prevalent in developing countries. The degree of toxicity reported in various extracts warrants further exploration of the cytotoxicity of the plant species, both against normal human cell lines and in vivo. Moreover, the acetylcholinesterase inhibitory and anti-inflammatory effects also need to be further

  6. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines.

    Science.gov (United States)

    Ru, Jinlong; Li, Peng; Wang, Jinan; Zhou, Wei; Li, Bohui; Huang, Chao; Li, Pidong; Guo, Zihu; Tao, Weiyang; Yang, Yinfeng; Xu, Xue; Li, Yan; Wang, Yonghua; Yang, Ling

    2014-01-01

    Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed. The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski's rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development. The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.

  7. Pharmacological treatment of the benign prostatic hyperplasia; Tratamiento farmacologico en la hiperplasia prostatica benigna

    Energy Technology Data Exchange (ETDEWEB)

    Perez Guerra, Yohani; Molina Cuevas, Vivian; Oyarzabal Yera, Ambar; Mas Ferreiro, Rosa, E-mail: yohani.perez@cnic.edu.c [Centro de Productos Naturales, Centro Nacional de Investigaciones Cientificas (CNIC), La Habana (Cuba)

    2011-07-01

    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 5{alpha}-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 a{alpha}{sub 1} -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5a{alpha}-reductase inhibitors, the a{alpha}{sub 1}-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 a{alpha}{sub 1}-adrenoceptor antagonist, a{alpha} 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

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

    Science.gov (United States)

    Lakatos, Péter

    2011-08-14

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

  9. Are pharmacological interventions between conception and birth effective in improving reproductive outcomes in North American swine?

    Science.gov (United States)

    Wessels, J M; Khalaj, K; Kridli, R T; Edwards, A K; Bidarimath, M; Tayade, C

    2014-08-01

    The objective of this review is to evaluate the effectiveness of using pharmacological compounds on reproductive outcomes, particularly litter size, in North American swine. While the opportunity to improve reproduction in North American pigs exists, numerous hurdles need to be overcome in order to achieve measureable results. In the swine industry, the majority of piglet losses are incurred during pregnancy and around farrowing. Over the last 20 years, a reduction in losses has been achieved through genetic selection and nutritional management; however, these topics are the focus of other reviews. This review will evaluate attempts to improve litter size by reducing losses at various stages of the reproductive process, from the time of conception to the time of farrowing, using pharmacological compounds. Generally, these compounds are used to either alter physiological processes related to fertilization, embryonic attachment or uterine capacity, etc., or to facilitate management aspects of the breeding females such as inducing parturition. Although some of the pharmacological agents reviewed here show some positive effects on improving reproductive parameters, the inconsistent results and associated risks usually outweigh the benefits gained. Thus, at the present time, the use of pharmacological agents to enhance reproduction in North American swine may only be recommended for herds with low fertility and presents an avenue of research that could be further explored. © 2014 Blackwell Verlag GmbH.

  10. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

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

    2015-07-01

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

  11. Effects of Red Wine Vinegar Beverage on the Colonic Tissue of Rodents: Biochemical, Functional and Pharmacological Analyses.

    Science.gov (United States)

    Enkhsaikhan, Azjargal; Takahara, Akira; Nakamura, Yuji; Goto, Ai; Chiba, Koki; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Naito, Atsuhiko T; Sugiyama, Atsushi

    2018-01-01

    A beverage made of red wine vinegar and grape juice (Yamanashi-no-megumi™) was developed as a supplemental fluid containing polyphenols, which has been clinically shown to enhance the colonic transit. In this study, we assessed the mechanism of its prokinetic action by analyzing the effects on both the colonic phosphodiesterase activity of rats (n=4) and the isolated colonic strip preparation of guinea pigs (n=4). The 7% (v/v) solution of the beverage significantly decreased the phosphodiesterase activity by 9% (n=4). The beverage in concentrations of 0.7, 2.1 and 7% (v/v) relaxed the colonic strips pre-contracted by 1 µmol/L of carbachol in a concentration-related manner with 50, 58 and 79%, each response of which was diminished to 11, 19 and 46%, respectively in the presence of 100 µmol/L of L-nitro-arginine methyl ester. These results obtained by biochemical, functional and pharmacological analyses suggest that the beverage could relax the colon through both cAMP-associated and nitric oxide-dependent pathways, which may partly explain clinically observed prokinetic effect of the beverage.

  12. Screening action potentials: The power of light

    Directory of Open Access Journals (Sweden)

    Lars eKaestner

    2011-07-01

    Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

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

    Science.gov (United States)

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

    2013-01-01

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

  14. Pharmacological analyses of learning and memory in zebrafish (Danio rerio).

    Science.gov (United States)

    Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

    2015-12-01

    Over the last decade, zebrafish (Danio rerio) have become valuable as a complementary model in behavioral pharmacology, opening a new avenue for understanding the relationships between drug action and behavior. This species offers a useful intermediate approach bridging the gap between in vitro studies and traditional mammalian models. Zebrafish offer great advantages of economy compared to their rodent counterparts, their complex brains and behavioral repertoire offer great translational potential relative to in vitro models. The development and validation of a variety of tests to measure behavior, including cognition, in zebrafish have set the stage for the use of this animal for behavioral pharmacology studies. This has led to research into the basic mechanisms of cognitive function as well as screening for potential cognition-improving drug therapies, among other lines of research. As with all models, zebrafish have limitations, which span pharmacokinetic challenges to difficulties quantifying behavior. The use, efficacy and limitations associated with a zebrafish model of cognitive function are discussed in this review, within the context of behavioral pharmacology. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Magallón Rosa

    2009-04-01

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

  16. Pharmacological consequences of oxidative stress in ocular tissues

    International Nuclear Information System (INIS)

    Ohia, Sunny E.; Opere, Catherine A.; LeDay, Angela M.

    2005-01-01

    The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H 2 O 2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H 2 O 2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [ 3 H] D-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H 2 O 2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma

  17. Pharmacological consequences of oxidative stress in ocular tissues

    Energy Technology Data Exchange (ETDEWEB)

    Ohia, Sunny E. [Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 141 Science and Research Building 2, University of Houston, Houston, TX 77204 (United States)]. E-mail: seohia@uh.edu; Opere, Catherine A. [Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE 68178 (United States); LeDay, Angela M. [Professional and Scientific Relations, Procter and Gamble Pharmaceuticals Inc., Mason, OH 45040 (United States)

    2005-11-11

    The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H{sub 2}O{sub 2} and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H{sub 2}O{sub 2} and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [{sup 3}H] D-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H{sub 2}O{sub 2} to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.

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

    Directory of Open Access Journals (Sweden)

    Nagano Celso S

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Pharmacologic perspectives of functional selectivity by the angiotensin II type 1 receptor

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Hansen, Jakob Lerche

    2008-01-01

    and to sudden injury occurring in the circulatory system. Hence, current drugs that block all AT(1) receptor actions most likely leave room for improvement. Recent developments show that two major signaling pathways used by the AT(1) receptor may be dissected by pharmacologic means. Key pathologic responses...... protein actions and simultaneous activation of G protein-dependent or -independent signaling could therefore be desirable in certain situations. The previously unappreciated concept of "functional selectivity" makes this exact strategy feasible and may yield improved drugs for cardiovascular therapy....

  1. Pharmacologic Evaluation of Antidepressant Activity and Synthesis of 2-Morpholino-5-phenyl-6H-1,3,4-thiadiazine Hydrobromide

    Directory of Open Access Journals (Sweden)

    Alexey P. Sarapultsev

    2016-05-01

    Full Text Available Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985, and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction.

  2. Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L. (Luobuma): A review.

    Science.gov (United States)

    Xie, Wenyan; Zhang, Xiaoying; Wang, Tian; Hu, Jianjun

    2012-05-07

    pharmacological effects and the mode of actions. Further safety assessments and clinical trials should be performed before it can be integrated into medicinal practices. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sidney J. Stohs

    2011-01-01

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

  4. Anti-inflammatory actions of acupuncture

    Directory of Open Access Journals (Sweden)

    Freek J. Zijlstra

    2003-01-01

    Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

  5. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

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

  6. Immunotropic aspect of the Bacillus coagulans probiotic action.

    Science.gov (United States)

    Bomko, Tatiana V; Nosalskaya, Tatiana N; Kabluchko, Tatiana V; Lisnyak, Yury V; Martynov, Artur V

    2017-08-01

    Currently, probiotics are increasingly used as the alternative to antibiotics as well as the preventive measures in humans. In particular, probiotics occupy a key position in the treatment of antibiotics-associated intestinal dysbiosis. A spore-forming microorganism lactobacillus Bacillus coagulans is one of the most promising probiotics. However, some of its pharmacological effects remain poorly understood. This study was aimed at investigation of the effect of B. coagulans (Laktovit Forte) on the intestinal dysbiosis syndrome in mice caused by streptomycin against the background of cyclophosphamide-induced cellular immunodeficiency. Pharmacological method: mouse model in vivo with immunodeficiency caused by cyclophosphamide. In mice with colitis caused by streptomycin treatment, the administration of B. coagulans (Laktovit Forte medicinal product) resulted in an antidiarrhoeal effect, normalisation of gastrointestinal motility and prevention of the animals' weight loss. Given the cyclophosphamide-induced immunosuppression and streptomycin-associated diarrhoea, the immunity was completely restored only under the action of B. coagulans. According to all parameters, B. coagulans has been proved to be more effective as compared to the Linex Forte reference product containing lacto- and bifidobacteria. © 2017 Royal Pharmaceutical Society.

  7. Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

    OpenAIRE

    dos Santos, Cintia Miranda; Campos, Jaqueline Ferreira; dos Santos, Helder Freitas; Balestieri, José Benedito Perrella; Silva, Denise Brentan; de Picoli Souza, Kely; Carollo, Carlos Alexandre; Estevinho, Leticia M.; dos Santos, Edson Lucas

    2017-01-01

    Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl...

  8. Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis

    International Nuclear Information System (INIS)

    Dimopoulou, Myrto; Verhoef, Aart; Pennings, Jeroen L.A.; Ravenzwaay, Bennard van; Rietjens, Ivonne M.C.M.; Piersma, Aldert H.

    2017-01-01

    Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID 10 (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants. • Retinoic

  9. Embryotoxic and pharmacologic potency ranking of six azoles in the rat whole embryo culture by morphological and transcriptomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dimopoulou, Myrto, E-mail: myrto.dimopoulou@wur.nl [Division of Toxicology, Wageningen University (Netherlands); National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Pennings, Jeroen L.A. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Ravenzwaay, Bennard van [Division of Toxicology, Wageningen University (Netherlands); BASF SE, Experimental Toxicology and Ecology, Ludwigshafen (Germany); Rietjens, Ivonne M.C.M. [Division of Toxicology, Wageningen University (Netherlands); Piersma, Aldert H. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Utrecht University, Utrecht (Netherlands)

    2017-05-01

    Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID{sub 10} (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants.

  10. Action-Effect Associations in Voluntary and Cued Task-Switching

    Science.gov (United States)

    Sommer, Angelika; Lukas, Sarah

    2018-01-01

    The literature of action control claims that humans control their actions in two ways. In the stimulus-based approach, actions are triggered by external stimuli. In the ideomotor approach, actions are elicited endogenously and controlled by the intended goal. In the current study, our purpose was to investigate whether these two action control modes affect task-switching differently. We combined a classical task-switching paradigm with action-effect learning. Both experiments consisted of two experimental phases: an acquisition phase, in which associations between task, response and subsequent action effects were learned and a test phase, in which the effects of these associations were tested on task performance by presenting the former action effects as preceding effects, prior to the task (called practiced effects). Subjects either chose freely between tasks (ideomotor action control mode) or they were cued as to which task to perform (sensorimotor action control mode). We aimed to replicate the consistency effect (i.e., task is chosen according to the practiced task-effect association) and non-reversal advantage (i.e., better task performance when the practiced effect matches the previously learned task-effect association). Our results suggest that participants acquired stable action-effect associations independently of the learning mode. The consistency effect (Experiment 1) could be shown, independent of the learning mode, but only on the response-level. The non-reversal advantage (Experiment 2) was only evident in the error rates and only for participants who had practiced in the ideomotor action control mode. PMID:29387027

  11. Pharmacological exploration of the resting membrane potential reserve

    DEFF Research Database (Denmark)

    van der Heyden, Marcel A G; Jespersen, Thomas

    2016-01-01

    as well as by exchangers and pumps. This review will focus on the relative and regulated contribution of IK1, IK,ACh and IK,Ca, and on pharmacological modification of the channels underlying these currents in respect to the resting membrane potential, Na(+) channel availability and atrial......The cardiac action potential arises and spreads throughout the myocardium as a consequence of highly organized spatial and temporal expression of ion channels conducting Na(+), Ca(2+) or K(+) currents. The cardiac Na(+) current is responsible for the initiation and progression of the action...... potential. Altered Na(+) current has been found implicated in a number of different arrhythmias, including atrial fibrillation. In the atrium, the resting membrane potential is more depolarized than in the ventricles, and as cardiac Na(+) channels undergo voltage-dependent inactivation close...

  12. Monovalent cations transfer through isolated human amnion: a new pharmacological model

    Energy Technology Data Exchange (ETDEWEB)

    Bara, M.; Guiet-Bara, A.; Durlach, J.

    1985-04-01

    Transfer of monovalent cations through the isolated human amnion consists of different factors: paracellular, coupling, ATPase dependent cellular transfer, leak cellular transfer. Understanding this transfer permits testing of the action of various substances. Physiological substances (Mg, taurine) increase ionic transfer and there is a vicarious effect between Mg and taurine. The tocolytic agents MgSO/sub 4/ and ethanol do not exhibit a good effect on the transfer: decrease with ethanol; equality between entry and exit fluxes with MgSO/sub 4/. On the other hand, amphotericin B increases mother-to-fetus transfer. Polluting metals (Pb, Cd, Hg, As) dramatically reduce exchanges and almost completely inhibit amnion permeability. Ingestion of ethanol also exhibits a dramatic effect on the exchange between mother and fetus through the amnion. Study of ionic transfer in vitro can be considered a pharmacological model to investigate the modifications of mother-fetus exchanges by various substances.

  13. Regulative effects of curcumin spice administration on gut microbiota and its pharmacological implications

    OpenAIRE

    Shen, Liang; Liu, Lu; Ji, Hong-Fang

    2017-01-01

    ABSTRACT Curcumin, the major active component of turmeric (Curcuma longa), is widely used as a spice and food-coloring agent, and also exhibits multiple biological activities. However, as curcumin has poor systemic bioavailability its pharmacology remains to be elucidated. Owing to the high concentration of curcumin in the gastrointestinal tract after oral administration, we hypothesize that it may exert regulative effects on the gut microbiota. We investigated the regulative effects of oral ...

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

    Science.gov (United States)

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-04-01

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

  15. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

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

  16. Gene specific actions of thyroid hormone receptor subtypes.

    Directory of Open Access Journals (Sweden)

    Jean Z Lin

    Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.

  17. Pharmacology profiling of chemicals and proteins

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl

    between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing....... This limitation complicates adverse effect assessment in the early drug-development phase, thus contributing to drugattrition. Prediction models offer the possibility to close these gaps and provide more complete pharmacology profiles, however improvements in performances are required for these tools to serve...... to its nonself origin, which potentially alters the pharmacology profile of the substance. The neutralization of biopharmaceuticals by antidrug antibodies (ADAs) is an important element in the immune response cascade, however studies of ADA binding site on biopharmaceuticals, referred to as B...

  18. Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

    Science.gov (United States)

    de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro

    2017-04-01

    D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  1. Illicium verum: a review on its botany, traditional use, chemistry and pharmacology.

    Science.gov (United States)

    Wang, Guo-Wei; Hu, Wen-Ting; Huang, Bao-Kang; Qin, Lu-Ping

    2011-06-14

    The fruit of Illicium verum Hook. f. (Chinese star anise) has long been used in traditional Chinese medicine and food industry with the actions of dispelling cold, regulating the flow of Qi and relieving pain. A bibliographic investigation was carried out by analyzing recognized books including Chinese herbal classic, and worldwide accepted scientific databases (Pubmed, SciFinder, Scopus and Web of Science) were searched for the available information on I. verum. I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes. Traditional uses of I. verum are recorded throughout Asia and Northern America, where it has been used for more than 10 types of disorders. Numerous compounds including volatiles, seco-prezizaane-type sesquiterpenes, phenylpropanoids, lignans, flavonoids and other constituents have been identified from I. verum. Modern pharmacology studies demonstrated that its crude extracts and active compounds possess wide pharmacological actions, especially in antimicrobial, antioxidant, insecticidal, analgesic, sedative and convulsive activities. In addition, it is the major source of shikimic acid, a primary ingredient in the antiflu drug (Tamiflu). This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of I. verum together with the toxicology, and discusses the possible trend and scope for future research of I. verum. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Pharmacological Blockade of Adenosine A2A but Not A1 Receptors Enhances Goal-Directed Valuation in Satiety-Based Instrumental Behavior

    Directory of Open Access Journals (Sweden)

    Yan Li

    2018-04-01

    Full Text Available The balance and smooth shift between flexible, goal-directed behaviors and repetitive, habitual actions are critical to optimal performance of behavioral tasks. The striatum plays an essential role in control of goal-directed versus habitual behaviors through a rich interplay of the numerous neurotransmitters and neuromodulators to modify the input, processing and output functions of the striatum. The adenosine receptors (namely A2AR and A1R, with their high expression pattern in the striatum and abilities to interact and integrate dopamine, glutamate and cannabinoid signals in the striatum, may represent novel therapeutic targets for modulating instrumental behavior. In this study, we examined the effects of pharmacological blockade of the A2ARs and A1Rs on goal-directed versus habitual behaviors in different information processing phases of instrumental learning using a satiety-based instrumental behavior procedure. We found that A2AR antagonist acts at the coding, consolidation and expression phases of instrumental learning to modulate animals’ sensitivity to goal-directed valuation without modifying action-outcome contingency. However, pharmacological blockade and genetic knockout of A1Rs did not affect acquisition or sensitivity to goal-valuation of instrumental behavior. These findings provide pharmacological evidence for a potential therapeutic strategy to control abnormal instrumental behaviors associated with drug addiction and obsessive-compulsive disorder by targeting the A2AR.

  3. Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects

    Science.gov (United States)

    Kovarik, John M; Schmouder, Robert; Barilla, Denise; Wang, Yibin; Kraus, Gerolf

    2004-01-01

    Aims FTY720 is a sphingosine-1-phosphate receptor agonist that redirects lymphocytes from the circulation to lymph nodes without impairing lymphocyte function. It is being developed as an immunomodulator for the prevention of acute rejection after organ transplantation. This study was performed to provide guidance on administration with respect to meals and to measure pharmacologic responses in healthy subjects. Methods In this randomized, two-period, crossover study, 14 healthy subjects received placebo on day −1 of each period with baseline circadian measurements of lymphocyte count and heart rate. Subjects subsequently received a single 1 mg oral dose of FTY720 on day 1 under fasting conditions and after a high fat meal. Blood FTY720 concentrations, lymphocyte count, and supine heart rate were assessed over an 8 day period after each FTY720 dose. The effect of food on FTY720 pharmacokinetics was assessed by standard bioequivalence testing. Results Both the peak concentration (0.65 ± 0.17 vs 0.64 ± 0.18 ng ml−1) and total exposure (AUC 149 ± 65 vs 139 ± 43 ng ml−1 h) did not differ significantly between fasting and fed states, respectively. The corresponding fed/fasting ratios and 90% confidence intervals were 1.00 (0.86, 1.17) for Cmax and 0.98 (0.86, 1.11) for AUC. Under both treatment conditions peripheral blood lymphocyte count decreased from baseline by 38 ± 9% over the first 2 days postdose and then increased towards predose values over the subsequent week. Whereas a circadian rhythm in supine heart rate was preserved in the presence of FTY720, the heart rate vs time curve was shifted downwards by 10% over the first day postdose and then recovered to prestudy values by days 3–5 postdose. These changes were asymptomatic. Conclusions Single 1 mg doses of FTY720 were well tolerated in healthy subjects and elicited a moderate decrease in peripheral blood lymphocyte count and a transient decrease in heart rate consistent with its pharmacological

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

    Science.gov (United States)

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

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

  5. Medicinal Uses, Phytochemistry, and Pharmacology of Origanum onites (L.): A Review.

    Science.gov (United States)

    Tepe, Bektas; Cakir, Ahmet; Sihoglu Tepe, Arzuhan

    2016-05-01

    Origanum onites L., known as Turkish oregano, has great traditional, medicinal, preservative, and commercial importance. It is used for the treatment of several kinds of ailments, such as gastrointestinal disorders, diabetes, high cholesterol, leukemia, bronchitis, etc. In this review, traditional use, phytochemistry, and pharmacology of O. onites reported between 1988 and 2014 were discussed. This review was prepared based on literature survey on scientific journals and books from libraries and electronic sources, such as Web of Science, PubMed, Scopus, Google Scholar, etc. All databases were searched up to June 2014. Several different classes of terpenoids, triterpene acids, phenolic acids, hydroquinones, flavonoids, hydrocarbons, sterols, pigments, fatty acids, tocopherols, and inorganic compounds were detected mainly in the aerial parts of this plant. Pharmacological studies revealed that extracts obtained from several solvents and individual compounds exhibited antimicrobial, antiviral, antioxidant, insecticidal, anticancer, hepatoprotective, genotoxic, antidiabetic, cholinesterase inhibitory, anti-inflammatory, analgesic activities, etc. O. onites, in general, exhibited remarkable activity potential in almost all test systems. The results of toxicity studies indicated that O. onites did not show any significant toxicity and mutagenicity on Drosophila and Salmonella. Toxicity of the extracts/essential oils and also individual compounds should be evaluated on mammalian cells to ensure their safety. The bioactivity of individual compounds aside from terpenoids should also be assessed in detail. Additionally, mode of action for the bioactive compounds should be evaluated to understand the complex pharmacological effects of these phytochemicals. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

  6. Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions

    Directory of Open Access Journals (Sweden)

    Seung-Yeol eNah

    2015-10-01

    Full Text Available Ginseng, the root of Panax ginseng, is used as a traditional medicine. Despite the long history of the use of ginseng, there is no specific scientific or clinical rationale for ginseng pharmacology besides its application as a general tonic. The ambiguous description of ginseng pharmacology might be due to the absence of a predominant active ingredient that represents ginseng pharmacology. Recent studies show that ginseng abundantly contains lysophosphatidic acids (LPAs, which are phospholipid-derived growth factor with diverse biological functions including those claimed to be exhibited by ginseng. LPAs in ginseng form a complex with ginseng proteins, which can bind and deliver LPA to its cognate receptors with a high affinity. As a first messenger, gintonin produces second messenger Ca2+ via G protein-coupled LPA receptors. Ca2+ is an intracellular mediator of gintonin and initiates a cascade of amplifications for further intercellular communications by activation of Ca2+-dependent kinases, receptors, gliotransmitter and neurotransmitter release. Ginsenosides, which have been regarded as primary ingredients of ginseng, cannot elicit intracellular [Ca2+]i transients, since they lack specific cell surface receptor. However, ginsenosides exhibit non-specific ion channel and receptor regulations. This is the key characteristic that distinguishes gintonin from ginsenosides. Although the current discourse on ginseng pharmacology is focused on ginsenosides, gintonin can definitely provide a mode of action for ginseng pharmacology that ginsenosides cannot. This review article introduces a novel concept of ginseng ligand-LPA receptor interaction and proposes to establish a paradigm that shifts the focus from ginsenosides to gintonin as a major ingredient representing ginseng pharmacology.

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

    Science.gov (United States)

    Couvineau, Alain; Laburthe, Marc

    2012-05-01

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

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

    Science.gov (United States)

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

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

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

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2013-08-01

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

  10. Efficacy of Neurofeedback Versus Pharmacological Support in Subjects with ADHD.

    Science.gov (United States)

    González-Castro, Paloma; Cueli, Marisol; Rodríguez, Celestino; García, Trinidad; Álvarez, Luis

    2016-03-01

    Behavioral training in neurofeedback has proven to be an essential complement to generalize the effects of pharmacological support in subjects who have attention deficit with hyperactivity disorder (ADHD). Therefore, this investigation attempts to analyze the efficacy of neurofeedback compared with pharmacological support and the combination of both. Participants were 131 students, classified into four groups: control (did not receive neurofeedback or pharmacological support), neurofeedback group, pharmacological support group, and combined group (neurofeedback + pharmacological support). Participants' executive control and cortical activation were assessed before and after treatment. Results indicate that the combined group obtained more benefits and that the neurofeedback group improved to a greater extent in executive control than the pharmacological support group. It is concluded that this kind of training may be an alternative to stimulate activation in subjects with ADHD.

  11. Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action.

    Science.gov (United States)

    Bhavnani, Bhagu R; Stanczyk, Frank Z

    2014-07-01

    Oral conjugated equine estrogens (CEE) are the most used estrogen formulation for postmenopausal hormone therapy either alone or in combination with a progestin. CEE is most commonly used for the management of early menopausal symptoms such as hot flashes, vaginitis, insomnia, and mood disturbances. Additionally, if used at the start of the menopausal phase (age 50-59 years), CEE prevents osteoporosis and may in some women reduce the risk of cardiovascular disease (CVD) and Alzheimer's disease (AD). There appears to be a common mechanism through which estrogens can protect against CVD and AD. CEE is a natural formulation of an extract prepared from pregnant mares' urine. The product monogram lists the presence of only 10 estrogens consisting of the classical estrogens, estrone and 17β-estradiol, and a group of unique ring B unsaturated estrogens such as equilin and equilenin. The ring B unsaturated estrogens are formed by an alternate steroidogenic pathway in which cholesterol is not an obligatory intermediate. Both the route of administration and structure of these estrogens play a role in the overall pharmacology of CEE. In contrast to 17β-estradiol, ring B unsaturated estrogens express their biological effects mainly mediated by the estrogen receptor β and not the estrogen receptor α. All estrogen components of CEE are antioxidants, and some ring B unsaturated estrogens have several fold greater antioxidant activity than estrone and 17β-estradiol. The cardioprotective and neuroprotective effects of CEE appear to be, to some extent, due to its ability to prevent the formation of oxidized LDL and HDL, and by inhibiting or modulating some of the key proteases involved in programmed cell death (apoptosis) induced by the excess neurotransmitter glutamate and other neurotoxins. Selective combinations of ring B unsaturated estrogens have the potential of being developed as novel therapeutic agents for the prevention of cardiovascular disease and Alzheimer

  12. Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.

    Science.gov (United States)

    Chua, Thiam; Eise, Nicole T; Simpson, Jamie S; Ventura, Sabatino

    2014-03-14

    Saw palmetto (Serenoa repens) was first used medicinally by native American Indians to treat urological disorders. Nowadays, saw palmetto extracts are widely used in Europe and North America to treat the urinary symptoms associated with benign prostatic hyperplasia even though its mechanisms of action are poorly understood. This study aimed to characterize the bioactive constituents of a lipid extract of saw palmetto that are able to affect contractility of the rat prostate gland. The mechanism of action will also be investigated. A commercially available lipid extract of saw palmetto was subjected to fractionation using normal phase column chromatography. Composition of fractions was assessed by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and mass spectrometry (MS). Contractile activities of these fractions were evaluated pharmacologically using isolated preparations of rat prostate gland and compared to the activity of the crude extract. Saw palmetto extract inhibited contractions of the rat prostate gland which were consistent with smooth muscle relaxant activity. Only the ethyl acetate fraction resulting from chromatography inhibited contractions of isolated rat prostates similarly to the inhibition produced by the crude lipid extract. Comparison with authentic samples and analysis of NMR data revealed that this bioactivity was due to the fatty acid components present in the ethyl acetate fraction. Bioassay using various pharmacological tools identified multiple contractile mechanisms which were affected by the bioactive constituents. A fatty acid component of saw palmetto extract causes inhibition of prostatic smooth muscle contractions via a non-specific mechanism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Diclofenac: an update on its mechanism of action and safety profile.

    Science.gov (United States)

    Gan, Tong J

    2010-07-01

    Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA). Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate. This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug's pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety. Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are

  14. Perinatal pharmacology: applications for neonatal neurology.

    Science.gov (United States)

    Smits, Anne; Allegaert, Karel

    2011-11-01

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

  15. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  16. How research in behavioral pharmacology informs behavioral science.

    Science.gov (United States)

    Branch, Marc N

    2006-05-01

    Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its conceptualizations and theory. In this article, I outline three general strategies in behavioral pharmacology research that have been employed to increase understanding of behavioral processes. Examples are provided of the general characteristics of the strategies and of implications of previous research for behavior theory. Behavior analysis will advance as its theories are challenged.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Botany, ethnomedicines, phytochemistry and pharmacology of Himalayan paeony (Paeonia emodi Royle.).

    Science.gov (United States)

    Ahmad, Mushtaq; Malik, Khafsa; Tariq, Akash; Zhang, Guolin; Yaseen, Ghulam; Rashid, Neelam; Sultana, Shazia; Zafar, Muhammad; Ullah, Kifayat; Khan, Muhammad Pukhtoon Zada

    2018-06-28

    Himalayan paeony (Paeonia emodi Royle.) is an important species used to treat various diseases. This study aimed to compile the detailed traditional medicinal uses, phytochemistry, pharmacology and toxicological investigations on P. emodi. This study also highlights taxonomic validity, quality of experimental designs and shortcomings in previously reported information on Himalayan paeony. The data was extracted from unpublished theses (Pakistan, China, India and Nepal), and different published research articles confined to pharmacology, phytochemistry and antimicrobial activities using different databases through specific keywords. The relevant information regarding medicinal uses, taxonomic/common names, part used, collection and identification source, authentication, voucher specimen number, plant extracts and their characterization, isolation and identification of phytochemicals, methods of study in silico, in vivo or in vitro, model organism used, dose and duration, minimal active concentration, zone of inhibition (antimicrobial study), bioactive compound(s), mechanism of action on single or multiple targets, and toxicological information. P. emodi is reported for diverse medicinal uses with pharmacological properties like antioxidant, nephroprotective, lipoxygenase inhibitory, cognition and oxidative stress release, cytotoxic, anti-inflammatory, antiepileptic, anticonvulsant, haemaglutination, alpha-chymotrypsin inhibitory, hepatoprotective, hepatic chromes and pharmacokinetics of carbamazepine expression, β-glucuronidase inhibitory, spasmolytic and spasmogenic, and airway relaxant. Data confined to its taxonomic validity, shows 10% studies with correct taxonomic name while 90% studies with incorrect taxonomic, pharmacopeial and common names. The literature reviewed, shows lack of collection source (11 reports), without proper source of identification (15 reports), 33 studies without voucher specimen number, 26 reports lack information on authentic herbarium

  19. Pharmacological activity of salvinorin A, the major component of Salvia divinorum.

    Science.gov (United States)

    Listos, Joanna; Merska, Alicja; Fidecka, Sylwia

    2011-01-01

    The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.

  20. Effective 1.0: An Analytic Effective Action Analysis Library

    OpenAIRE

    Hetherington, James P. J.; Stephens, Philip

    2006-01-01

    Effective is a C++ library which provides the user a toolbox to study the effective action of an arbitrary field theory. From the field content, gauge groups and representations an appropriate action is generated symbolically. The effective potential, mass spectrum, field couplings and vacuum expectation values are then obtained automatically; tree level results are obtained analytically while many tools, both numeric and analytic, provide a variety of approaches to deal with the one-loop cor...

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

    International Nuclear Information System (INIS)

    Kirillova, E.N.; Muksinova, K.N.; Revina, V.; Smirnov, D.; Sokolnikov, M.; Lukyanova, T.

    1996-01-01

    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)

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

    Science.gov (United States)

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

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

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

    Directory of Open Access Journals (Sweden)

    Shoude Zhang

    2014-01-01

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

  4. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  5. Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis.

    Science.gov (United States)

    Florez, Diego Hernando Ângulo; Dos Santos Moreira, Ana Maria; da Silva, Pedro Rafael; Brandão, Ricardo; Borges, Marcella Matos Cordeiro; de Santana, Fernando José Malagueño; Borges, Keyller Bastos

    2017-04-01

    "Krokodil" or "Crocodile" is an illegal homemade desomorphine drug obtained from chemical reactions of commercial codeine drugs with several other powerful and highly toxic chemical agents increasing its addiction and hallucinogenic effects when compared with other morphine analogues. This paper summarizes a complete review about an old drug called desomorphine (Krokodil), presenting its chemistry, pharmacology, metabolism, toxicology and analysis. It is of particular interest and concern because this cheaper injectable semisynthetic opioid drug has been largely used in recent years for recreational purposes in several Eastern European as well as North and South American countries, despite known damage to health that continuous use might induce. These injuries are much stronger and more aggressive than morphine's, infecting and rotting skin and soft tissue to the bone of addicts at the point of injection in less than three years, which, in most cases, evolves to death. On this basis, it is imperative that literature reviews focus on the chemistry, pharmacology, toxicology and analysis of dangerous Krokodil to find strategies for rapid and effective determination to mitigate its adverse effects on addicts and prevent consumption. It is crucial to know the symptoms and consequences of the use of Krokodil, as well as METHODS: for identification and quantification of desomorphine, contaminants and metabolites, which can help the forensic work of diagnosis and propose actions to control and eradicate this great danger to public health around the world. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Pharmacological properties of Salvia officinalis and its components

    Directory of Open Access Journals (Sweden)

    Ahmad Ghorbani

    2017-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Iandra Holzmann

    2011-01-01

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

  8. Providing data science support for systems pharmacology and its implications to drug discovery.

    Science.gov (United States)

    Hart, Thomas; Xie, Lei

    2016-01-01

    The conventional one-drug-one-target-one-disease drug discovery process has been less successful in tracking multi-genic, multi-faceted complex diseases. Systems pharmacology has emerged as a new discipline to tackle the current challenges in drug discovery. The goal of systems pharmacology is to transform huge, heterogeneous, and dynamic biological and clinical data into interpretable and actionable mechanistic models for decision making in drug discovery and patient treatment. Thus, big data technology and data science will play an essential role in systems pharmacology. This paper critically reviews the impact of three fundamental concepts of data science on systems pharmacology: similarity inference, overfitting avoidance, and disentangling causality from correlation. The authors then discuss recent advances and future directions in applying the three concepts of data science to drug discovery, with a focus on proteome-wide context-specific quantitative drug target deconvolution and personalized adverse drug reaction prediction. Data science will facilitate reducing the complexity of systems pharmacology modeling, detecting hidden correlations between complex data sets, and distinguishing causation from correlation. The power of data science can only be fully realized when integrated with mechanism-based multi-scale modeling that explicitly takes into account the hierarchical organization of biological systems from nucleic acid to proteins, to molecular interaction networks, to cells, to tissues, to patients, and to populations.

  9. Pharmacological aspects of release from microcapsules - from polymeric multilayers to lipid membranes.

    Science.gov (United States)

    Wuytens, Pieter; Parakhonskiy, Bogdan; Yashchenok, Alexey; Winterhalter, Mathias; Skirtach, Andre

    2014-10-01

    This review is devoted to pharmacological applications of principles of release from capsules to overcome the membrane barrier. Many of these principles were developed in the context of polymeric multilayer capsule membrane modulation, but they are also pertinent to liposomes, polymersomes, capsosomes, particles, emulsion-based carriers and other carriers. We look at these methods from the physical, chemical or biological driving mechanisms point of view. In addition to applicability for carriers in drug delivery, these release methods are significant for another area directly related to pharmacology - modulation of the permeability of the membranes and thus promoting the action of drugs. Emerging technologies, including ionic current monitoring through a lipid membrane on a nanopore, are also highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

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

  11. Acupuncture's Role in Solving the Opioid Epidemic: Evidence, Cost-Effectiveness, and Care Availability for Acupuncture as a Primary, Non-Pharmacologic Method for Pain Relief and Management-White Paper 2017.

    Science.gov (United States)

    Fan, Arthur Yin; Miller, David W; Bolash, Bonnie; Bauer, Matthew; McDonald, John; Faggert, Sarah; He, Hongjian; Li, Yong Ming; Matecki, Amy; Camardella, Lindy; Koppelman, Mel Hopper; Stone, Jennifer A M; Meade, Lindsay; Pang, John

    2017-11-01

    The United States (U.S.) is facing a national opioid epidemic, and medical systems are in need of non-pharmacologic strategies that can be employed to decrease the public's opioid dependence. Acupuncture has emerged as a powerful, evidence-based, safe, cost-effective, and available treatment modality suitable to meeting this need. Acupuncture has been shown to be effective for the management of numerous types of pain conditions, and mechanisms of action for acupuncture have been described and are understandable from biomedical, physiologic perspectives. Further, acupuncture's cost-effectiveness can dramatically decrease health care expenditures, both from the standpoint of treating acute pain and through avoiding addiction to opioids that requires costly care, destroys quality of life, and can lead to fatal overdose. Numerous federal regulatory agencies have advised or mandated that healthcare systems and providers offer non-pharmacologic treatment options for pain. Acupuncture stands out as the most evidence-based, immediately available choice to fulfil these calls. Acupuncture can safely, easily, and cost-effectively be incorporated into hospital settings as diverse as the emergency department, labor and delivery suites, and neonatal intensive care units to treat a variety of commonly seen pain conditions. Acupuncture is already being successfully and meaningfully utilized by the Veterans Administration and various branches of the U.S. Military, in some studies demonstrably decreasing the volume of opioids prescribed when included in care.

  12. Pharmacological preconditioning by milrinone: memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Saklani, Reetu; Jaggi, Amteshwar; Singh, Nirmal

    2010-07-01

    We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 microg/kg & 100 microg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.

  13. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae

    Directory of Open Access Journals (Sweden)

    Panthati Murali Krishna

    2012-10-01

    Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.

  14. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae

    Directory of Open Access Journals (Sweden)

    Panthati Murali Krishna

    2012-04-01

    Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.

  15. Pharmacological screening of Malian medicinal plants used against epilepsy and convulsions

    DEFF Research Database (Denmark)

    Pedersen, Mikael E; Vestergaard, Henrik T; Hansen, Suzanne L

    2009-01-01

    Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants.......Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants....

  16. Long-term and short-term action-effect links and their impact on effect monitoring.

    Science.gov (United States)

    Wirth, Robert; Steinhauser, Robert; Janczyk, Markus; Steinhauser, Marco; Kunde, Wilfried

    2018-04-23

    People aim to produce effects in the environment, and according to ideomotor theory, actions are selected and executed via anticipations of their effects. Further, to ensure that an action has been successful and an effect has been realized, we must be able to monitor the consequences of our actions. However, action-effect links might vary between situations, some might apply for a majority of situations, while others might only apply to special occasions. With a combination of behavioral and electrophysiological markers, we show that monitoring of self-produced action effects interferes with other tasks, and that the length of effect monitoring is determined by both, long-term action-effect links that hold for most situations, and short-term action-effect links that emerge from a current setting. Effect monitoring is fast and frugal when these action-effect links allow for valid anticipation of action effects, but otherwise effect monitoring takes longer and delays a subsequent task. Specific influences of long-term and short-term links on the P1/N1 and P3a further allow to dissect the temporal dynamics of when these links interact for the purpose of effect monitoring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  17. Assessing the effects of pharmacological agents on respiratory dynamics using time-series modeling.

    Science.gov (United States)

    Wong, Kin Foon Kevin; Gong, Jen J; Cotten, Joseph F; Solt, Ken; Brown, Emery N

    2013-04-01

    Developing quantitative descriptions of how stimulant and depressant drugs affect the respiratory system is an important focus in medical research. Respiratory variables-respiratory rate, tidal volume, and end tidal carbon dioxide-have prominent temporal dynamics that make it inappropriate to use standard hypothesis-testing methods that assume independent observations to assess the effects of these pharmacological agents. We present a polynomial signal plus autoregressive noise model for analysis of continuously recorded respiratory variables. We use a cyclic descent algorithm to maximize the conditional log likelihood of the parameters and the corrected Akaike's information criterion to choose simultaneously the orders of the polynomial and the autoregressive models. In an analysis of respiratory rates recorded from anesthetized rats before and after administration of the respiratory stimulant methylphenidate, we use the model to construct within-animal z-tests of the drug effect that take account of the time-varying nature of the mean respiratory rate and the serial dependence in rate measurements. We correct for the effect of model lack-of-fit on our inferences by also computing bootstrap confidence intervals for the average difference in respiratory rate pre- and postmethylphenidate treatment. Our time-series modeling quantifies within each animal the substantial increase in mean respiratory rate and respiratory dynamics following methylphenidate administration. This paradigm can be readily adapted to analyze the dynamics of other respiratory variables before and after pharmacologic treatments.

  18. Early markers of ongoing action-effect learning

    Directory of Open Access Journals (Sweden)

    Hannes eRuge

    2012-11-01

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

  19. Studying of the standardization principles of pharmacological activity of recombinant erythropoietin preparations

    OpenAIRE

    A. K. Yakovlev; L. A. Gayderova; N. A. Alpatova; T. N. Lobanova; E. L. Postnova; E. I. Yurchikova; T. A. Batuashvili; R. A. Volkova; V. N. Podkuiko; Yu. V. Olefir

    2016-01-01

    Analysis of the publications devoted to the structure, functions, mechanism of action of erythropoietin is given in the article. Erythropoietin preparations derived from recombinant DNA technology are a mixture of isoforms with different biological activity, which determine the biological properties pharmacological activity, pharmacokinetics, efficacy and safety of medicinal product. Erythropoietin preparations derived by using recombinant DNA technology are a mixture of isoforms with differe...

  20. Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

    OpenAIRE

    Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

    2014-01-01

    Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group ...

  1. Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora Palau.

    Science.gov (United States)

    Abuhamdah, Sawsan; Abuhamdah, Rushdie; Howes, Melanie-Jayne R; Al-Olimat, Suleiman; Ennaceur, Abdel; Chazot, Paul L

    2015-09-01

    The Jordanian 'Melissa', (Aloysia citrodora) has been poorly studied both pharmacologically and in the clinic. Essential oils (EO) derived from leaves of A. citrodora were obtained by hydrodistillation, analysed by gas chromatography-mass spectrometry (GC-MS) and were investigated for a range of neurobiological and pharmacological properties, as a basis for potential future use in drug discovery. A selection of central nervous system (CNS) receptor-binding profiles was carried out. Antioxidant activity and ferrous iron-chelating assays were adopted, and the neuroprotective properties of A. citrodora EO assessed using hydrogen peroxide-induced and β-amyloid-induced neurotoxicity with the CAD (Cath.-a-differentiated) neuroblastoma cell line. The major chemical components detected in the A. citrodora EOs, derived from dried and fresh leaves, included limonene, geranial, neral, 1, 8-cineole, curcumene, spathulenol and caryophyllene oxide, respectively. A. citrodora leaf EO inhibited [(3) H] nicotine binding to well washed rat forebrain membranes, and increased iron-chelation in vitro. A. citrodora EO displays effective antioxidant, radical-scavenging activities and significant protective properties vs both hydrogen peroxide- and β-amyloid-induced neurotoxicity. A. citrodora EO displays a range of pharmacological properties worthy of further investigation to isolate the compounds responsible for the observed neuroactivities, to further analyse their mode of action and determine their clinical potential in neurodegenerative diseases. © 2015 Royal Pharmaceutical Society.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  3. Pharmacology Experiments on the Computer.

    Science.gov (United States)

    Keller, Daniel

    1990-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2013-12-01

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

  5. Anticipation of delayed action-effects: learning when an effect occurs, without knowing what this effect will be.

    Science.gov (United States)

    Dignath, David; Janczyk, Markus

    2017-09-01

    According to the ideomotor principle, behavior is controlled via a retrieval of the sensory consequences that will follow from the respective movement ("action-effects"). These consequences include not only what will happen, but also when something will happen. In fact, recollecting the temporal duration between response and effect takes time and prolongs the initiation of the response. We investigated the associative structure of action-effect learning with delayed effects and asked whether participants acquire integrated action-time-effect episodes that comprise a compound of all three elements or whether they acquire separate traces that connect actions to the time until an effect occurs and actions to the effects that follow them. In three experiments, results showed that participants retrieve temporal intervals that follow from their actions even when the identity of the effect could not be learned. Furthermore, retrieval of temporal intervals in isolation was not inferior to retrieval of temporal intervals that were consistently followed by predictable action-effects. More specifically, when tested under extinction, retrieval of action-time and action-identity associations seems to compete against each other, similar to overshadowing effects reported for stimulus-response conditioning. Together, these results suggest that people anticipate when the consequences of their action will occur, independently from what the consequences will be.

  6. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    Directory of Open Access Journals (Sweden)

    Chanin Clark Wright

    2013-12-01

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

  7. Some pharmacological effects of cinnamon and ginger herbs in obese diabetic rats

    Science.gov (United States)

    Shalaby, Mostafa Abbas; Saifan, Hamed Yahya

    2014-01-01

    Aims: The present study was designed to assess some pharmacological effects of cinnamon (CAE) and ginger (GAE) aqueous extracts in obese diabetic rats, and to elucidate the potential mechanisms. Materials and Methods: Forty-two Sprague-Dawley rats were randomized into 6 equal groups. Group 1 was a negative control and the other groups were rendered obese by feeding rats on high-fat diet for 4 weeks. The obese rats were subcutaneously injected with alloxan for 5*days to induce diabetes. Group 2 was a positive control, and Groups 3, 4, 5 and 6 were orally given CAE in doses 200 and 400 mg/kg and GAE in the same doses, respectively for 6 weeks. Blood samples were collected for serum biochemical analyses. Kidneys were dissected out to assay activity of tissue antioxidant enzymes: Superoxide dismutase, glutathione peroxidase and catalase. Results: CAE and GAE significantly reduced body weight and body fat mass; normalized serum levels of liver enzymes; improved lipid profile; decreased blood glucose and leptin and increased insulin serum levels in obese diabetic rats. Both extracts also increased activity of kidney antioxidant enzymes. Conclusion: CAE and GAE exhibit anti-obesity, hepatoprotective, hypolipidemic, antidiabetic and anti-oxidant effects in obese diabetic rats. These results confirm the previous reports on both extracts. The potential mechanisms underlying these effects are fully discussed and clarified. Our results affirm the traditional use of cinnamon and ginger for treating patients suffering from obesity and diabetes. The obese diabetic rat model used in this study is a novel animal model used in pharmacology researches. PMID:26401364

  8. Dissociating action-effect activation and effect-based response selection.

    Science.gov (United States)

    Schwarz, Katharina A; Pfister, Roland; Wirth, Robert; Kunde, Wilfried

    2018-05-25

    Anticipated action effects have been shown to govern action selection and initiation, as described in ideomotor theory, and they have also been demonstrated to determine crosstalk between different tasks in multitasking studies. Such effect-based crosstalk was observed not only in a forward manner (with a first task influencing performance in a following second task) but also in a backward manner (the second task influencing the preceding first task), suggesting that action effect codes can become activated prior to a capacity-limited processing stage often denoted as response selection. The process of effect-based response production, by contrast, has been proposed to be capacity-limited. These observations jointly suggest that effect code activation can occur independently of effect-based response production, though this theoretical implication has not been tested directly at present. We tested this hypothesis by employing a dual-task set-up in which we manipulated the ease of effect-based response production (via response-effect compatibility) in an experimental design that allows for observing forward and backward crosstalk. We observed robust crosstalk effects and response-effect compatibility effects alike, but no interaction between both effects. These results indicate that effect activation can occur in parallel for several tasks, independently of effect-based response production, which is confined to one task at a time. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Francois eQuesque

    2013-10-01

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

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

    Science.gov (United States)

    Anand, K J S; Hall, R W

    2006-11-01

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

  11. Low-energy effective action for the superstring

    International Nuclear Information System (INIS)

    Burgess, C.P.; Font, A.; Quevedo, F.

    1986-01-01

    We construct the low-energy D=4, N=1 supergravity that arises in superstring theories for an arbitrary number of generations. The coupling of all massless modes that carry low-energy gauge quantum numbers are calculated by truncating the heavy Kaluza-Klein modes of the ten-dimensional effective field theory. The resulting action is compared to the most general effective action compatible with the symmetries of the underlying ten-dimensional field (and string) theories. This comparison indicates which features of the truncation correctly approximate the exact low-energy action. (orig.)

  12. Nambu sigma model and effective membrane actions

    Energy Technology Data Exchange (ETDEWEB)

    Jurco, Branislav, E-mail: jurco@karlin.mff.cuni.cz [Mathematical Institute, Charles University, Prague 186 75 (Czech Republic); Schupp, Peter, E-mail: p.schupp@jacobs-university.de [Jacobs University Bremen, 28759 Bremen (Germany); Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, Scotland (United Kingdom)

    2012-07-09

    We propose an effective action for a p{sup Prime }-brane with open p-branes ending on it. The action has dual descriptions similar to the commutative and non-commutative ones of the DBI action for D-branes and open strings. The Poisson structure governing the non-commutativity of the D-brane is replaced by a Nambu structure and the open-closed string relations are generalized to the case of p-branes utilizing a novel Nambu sigma model description of p-branes. In the case of an M5-brane our action interpolates between M5-actions already proposed in the literature and matrix-model like actions involving Nambu structures.

  13. Nambu sigma model and effective membrane actions

    International Nuclear Information System (INIS)

    Jurčo, Branislav; Schupp, Peter

    2012-01-01

    We propose an effective action for a p ′ -brane with open p-branes ending on it. The action has dual descriptions similar to the commutative and non-commutative ones of the DBI action for D-branes and open strings. The Poisson structure governing the non-commutativity of the D-brane is replaced by a Nambu structure and the open-closed string relations are generalized to the case of p-branes utilizing a novel Nambu sigma model description of p-branes. In the case of an M5-brane our action interpolates between M5-actions already proposed in the literature and matrix-model like actions involving Nambu structures.

  14. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    Science.gov (United States)

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Jatropha gossypiifolia L. (Euphorbiaceae: A Review of Traditional Uses, Phytochemistry, Pharmacology, and Toxicology of This Medicinal Plant

    Directory of Open Access Journals (Sweden)

    Juliana Félix-Silva

    2014-01-01

    Full Text Available Jatropha gossypiifolia L. (Euphorbiaceae, widely known as “bellyache bush,” is a medicinal plant largely used throughout Africa and America. Several human and veterinary uses in traditional medicine are described for different parts and preparations based on this plant. However, critical reviews discussing emphatically its medicinal value are missing. This review aims to provide an up-to-date overview of the traditional uses, as well as the phytochemistry, pharmacology, and toxicity data of J. gossypiifolia species, in view of discussing its medicinal value and potential application in complementary and alternative medicine. Pharmacological studies have demonstrated significant action of different extracts and/or isolated compounds as antimicrobial, anti-inflammatory, antidiarrheal, antihypertensive, and anticancer agents, among others, supporting some of its popular uses. No clinical trial has been detected to date. Further studies are necessary to assay important folk uses, as well as to find new bioactive molecules with pharmacological relevance based on the popular claims. Toxicological studies associated with phytochemical analysis are important to understand the eventual toxic effects that could reduce its medicinal value. The present review provides insights for future research aiming for both ethnopharmacological validation of its popular use and its exploration as a new source of herbal drugs and/or bioactive natural products.

  16. Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

    Science.gov (United States)

    Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

    2012-11-01

    MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  17. Pharmacological management of panic disorder

    Directory of Open Access Journals (Sweden)

    Carlo Marchesi

    2008-03-01

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

  18. The Effects of Combined Treadmill Training and Pharmacological Treatment on Management of Multiple Sclerosis Female Patients

    Directory of Open Access Journals (Sweden)

    Ali Asghar Arastoo

    2013-04-01

    Full Text Available Objectives: To compare the effectiveness of two treatment methods of ‘combination pharmacological treatment and treadmill training’ and ‘pharmacological treatment’ on management of multiple sclerosis (MS female patients. Methods: In this quasi experimental and interventional study a sample of 20 MS patients (mean age: 36.75 years with Expanded Disability Status Scale scores (EDSS 1.0 to 4.0 were randomly assigned to a ‘pharmacologic treatment’ (Ph group and a combination group of ‘pharmacologic treatment& treadmill training’ (PhTT. All these individuals used the drugs of choice ‘Rebif’ and ‘Avonex’. The intervention consisted of 8-weeks (24 sessions of treadmill training (30 minutes each, at 40-75% of age-predicted maximum heart rate for the PhTT group. The Ph group followed their own routine treatment program. Balance, speed and endurance of walking, quality of life and fatigue were measured by Berg Balance Score, 10 meter timed walk test, 2 minute walk test, and Fatigue Severity Scale (FFS. Data were analyzed by paired t test and one way ANOVA. Results: Comparison of results indicated that pre and post intervention led to significant improvements in the balance score (P=0.001, 10m walk time (P=0.001, walking endurance (P=0.007, and FFS (P=0.04 in the PhTT group. In contrast, no significant changes were observed in the Ph group’s balance score, 10m timed walk and fatigue, while there was a significant decrease in the 2min walking distance (P=0.015 in this group. Discussion: These results suggest that treadmill training in combination with pharmacological treatment improve balance and walking capacity and level of fatigue in women with mild to moderate MS.

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

    Science.gov (United States)

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

    2012-08-13

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

  20. Structure and pharmacological actions of phyllocaerulein, a caerulein-like nonapeptide: its occurrence in extracts of the skin of Phyllomedusa sauvagei and related Phyllomedusa species.

    Science.gov (United States)

    Anastasi, A; Bertaccini, G; Cei, J M; De Caro, G; Erspamer, V; Impicciatore, M

    1969-09-01

    1. The South American amphibian Phyllomedusa sauvagei contains in its skin large amounts of a polypeptide closely resembling caerulein in its pharmacological actions. This polypeptide, called phyllocaerulein, was obtained in a pure form, and upon acid hydrolysis, enzymic digestion and end-group determination experiments it proved to be a nonapeptide of the following composition Pyr-Glu-Tyr(SO(3)H)-Thr-Gly-Trp-Met-Asp-Phe-NH(2)It may be seen that caerulein and phyllocaerulein have in common the C-terminal heptapeptide and the N-terminal pyroglutamyl residue.2. Phyllocaerulein is indistinguishable from caerulein even in parallel bioassay. However, the former polypeptide seems to be somewhat more potent than the latter on all the preparations tested.3. In different batches of Phyllomedusa sauvagei skin the phyllocaerulein content ranged between 150 and 600 mug/g of fresh tissue.Phyllocaerulein or similar polypeptides occur also in the skin of several other Phyllomedusa species, among which are Phyll. burmeisteri, Phyll. dachnicolor, Phyll, helenae, Phyll. annae, Phyll. callidryas and Phyll. bicolor.4. The qualitative identification and quantitative estimation of caerulein-like polypeptides in crude skin extracts may be complicated by the concomitant occurrence of other active polypeptides. These, however, are poorly effective on some test preparations which seem to respond selectively to caerulein.5. Like that of caerulein, the biological significance of phyllocaerulein is completely obscure.

  1. Student engagement in pharmacology courses using online learning tools.

    Science.gov (United States)

    Karaksha, Abdullah; Grant, Gary; Anoopkumar-Dukie, Shailendra; Nirthanan, S Niru; Davey, Andrew K

    2013-08-12

    To assess factors influencing student engagement with e-tools used as a learning supplement to the standard curriculum in pharmacology courses. A suite of 148 e-tools (interactive online teaching materials encompassing the basic mechanisms of action for different drug classes) were designed and implemented across 2 semesters for third-year pharmacy students. Student engagement and use of this new teaching strategy were assessed using a survey instrument and usage statistics for the material. Use of e-tools during semester 1 was low, a finding attributable to a majority (75%) of students either being unaware of or forgetting about the embedded e-tools and a few (20%) lacking interest in accessing additional learning materials. In contrast to semester 1, e-tool use significantly increased in semester 2 with the use of frequent reminders and announcements (ponline teaching and learning resources were only effective in increasing student engagement after the implementation of a "marketing strategy" that included e-mail reminders and motivation.

  2. Influence of Action-Effect Associations Acquired by Ideomotor Learning on Imitation

    Science.gov (United States)

    Bunlon, Frédérique; Marshall, Peter J.; Quandt, Lorna C.; Bouquet, Cedric A.

    2015-01-01

    According to the ideomotor theory, actions are represented in terms of their perceptual effects, offering a solution for the correspondence problem of imitation (how to translate the observed action into a corresponding motor output). This effect-based coding of action is assumed to be acquired through action-effect learning. Accordingly, performing an action leads to the integration of the perceptual codes of the action effects with the motor commands that brought them about. While ideomotor theory is invoked to account for imitation, the influence of action-effect learning on imitative behavior remains unexplored. In two experiments, imitative performance was measured in a reaction time task following a phase of action-effect acquisition. During action-effect acquisition, participants freely executed a finger movement (index or little finger lifting), and then observed a similar (compatible learning) or a different (incompatible learning) movement. In Experiment 1, finger movements of left and right hands were presented as action-effects during acquisition. In Experiment 2, only right-hand finger movements were presented during action-effect acquisition and in the imitation task the observed hands were oriented orthogonally to participants’ hands in order to avoid spatial congruency effects. Experiments 1 and 2 showed that imitative performance was improved after compatible learning, compared to incompatible learning. In Experiment 2, although action-effect learning involved perception of finger movements of right hand only, imitative capabilities of right- and left-hand finger movements were equally affected. These results indicate that an observed movement stimulus processed as the effect of an action can later prime execution of that action, confirming the ideomotor approach to imitation. We further discuss these findings in relation to previous studies of action-effect learning and in the framework of current ideomotor approaches to imitation. PMID:25793755

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Variational methods and effective actions in string models

    International Nuclear Information System (INIS)

    Dereli, T.; Tucker, R.W.

    1987-01-01

    Effective actions motivated by zero-order and first-order actions are examined. Particular attention is devoted to a variational procedure that is consistent with the structure equations involving the Lorentz connection. Attention is drawn to subtleties that can arise in varying higher-order actions and an efficient procedure developed to handle these cases using the calculus of forms. The effect of constrained variations on the field equations is discussed. (author)

  5. GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, P; Frølund, B; Frydenvang, Karla Andrea

    2000-01-01

    demonstrated that neuronal and glial GABA transport mechanisms have dissimilar substrate specificities. With GABA transport mechanisms as pharmacological targets, strategies for pharmacological interventions with the purpose of stimulating GABA neurotransmission seem to be (1) effective blockade of neuronal......, tiagabine (49) containing (R)-nipecotic acid (24) as the GABA transport carrier-recognizing structure element, is now marketed as an antiepileptic agent....

  6. An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs).

    Science.gov (United States)

    Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

    2017-11-08

    LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

    Science.gov (United States)

    Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

    2015-01-01

    To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

  8. Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.

    Science.gov (United States)

    Galaup, Ariane; Paci, Angelo

    2013-03-01

    Among the dimethanesulfonates, busulfan, in combination with other alkylating agents or nucleoside analogues, is the cornerstone of high-dose chemotherapy. It is used, and followed hematopoietic stem cell transplantation, for the treatment of various hematologic malignancies and immunodeficiencies. Treosulfan, which is a hydrophilic analogue of busulfan, was the first dimethanesufonate registered for the treatment of ovarian cancer. Recently, treosulfan has been investigated for the treatment of hematologic malignancies in combination with the same second agents before hematopoietic stem cell transplantation. This work reviews the pharmacological data of these two dimethanesulfonates alkylating agents. Specifically, the article looks at their chemistry, metabolism, anticancer activity, and their pharmacokinetics and pharmacodynamics. Busulfan has been investigated widely for more than three decades leading to a large and precise handling of this agent with numerous studies on activity and pharmacokinetics and pharmacodynamics. In contrast, the behavior of treosulfan is still under investigation and not fully described. The complexity of treosulfan's metabolism and mechanism of action gives rise to the need of a deeper understanding of its pharmacological activity in a context of high-dose chemotherapy. Specifically, there is a great need to better understand its pharmacokinetics/pharmacodynamics relationship.

  9. A fast Na+/Ca2+-based action potential in a marine diatom.

    Directory of Open Access Journals (Sweden)

    Alison R Taylor

    Full Text Available BACKGROUND: Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and

  10. [Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

    Science.gov (United States)

    Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan

    2018-04-01

    The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides(Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.

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

    Directory of Open Access Journals (Sweden)

    Stefania S. Grigoriou

    2015-04-01

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

  12. Developing Effective Corrective Action Plan in Krsko NPP

    International Nuclear Information System (INIS)

    Bach, Bruno; Cizmek, Rudi; Bozin, Bojan

    2014-01-01

    Experience shows that many events could have been prevented if lessons had been learned from previous incidents. Event reporting thus has become an increasingly important aspect of the operation and regulation of all safety-related and public health industries. Different industries such as aeronautics, chemicals, transport and of course nuclear depend on Operating Experience (OE) feedback programs to provide lessons learned about safety. The information available under an OE programme for these organizations comprises internal event reports and analysis and external operating experience including reports on low level events and near misses and other relevant operating performance information. The worldwide OE programme (such as WANO OE) in nuclear power plants provides opportunity to learn from events at other plants. In particular, it alerts plants to mistakes or events that have occurred at other nuclear power plants and enables them to take corrective actions to prevent similar occurrences at their own plant. The intent of the effective and efficient OE program is therefore to improve personnel/plant safety, reliability and commercial performance of the operating nuclear power plants. Such a programme ensures that operating experience is analysed, events important to safety are reviewed in depth, lessons learned are disseminated to the staff and to the relevant national and international organizations and corrective actions are effectively implemented. Learning and applying the lessons from operating experience is an integral part of station safety culture and is encouraged by managers throughout the top plant administrative programs and procedures. Krsko NPP is developed its own OE program by using the most relevant INPO/WANO/IAEA guidelines as well as its own knowledge, skills an operating practice. The OE is a part of the Corrective Action Program (CAP), which is among top management programs. The purpose of this article is to present a part of the Krško NPP

  13. Cost-effectiveness analysis of left atrial appendage occlusion compared with pharmacological strategies for stroke prevention in atrial fibrillation.

    Science.gov (United States)

    Lee, Vivian Wing-Yan; Tsai, Ronald Bing-Ching; Chow, Ines Hang-Iao; Yan, Bryan Ping-Yen; Kaya, Mehmet Gungor; Park, Jai-Wun; Lam, Yat-Yin

    2016-08-31

    Transcatheter left atrial appendage occlusion (LAAO) is a promising therapy for stroke prophylaxis in non-valvular atrial fibrillation (NVAF) but its cost-effectiveness remains understudied. This study evaluated the cost-effectiveness of LAAO for stroke prophylaxis in NVAF. A Markov decision analytic model was used to compare the cost-effectiveness of LAAO with 7 pharmacological strategies: aspirin alone, clopidogrel plus aspirin, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban. Outcome measures included quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratios (ICERs). Base-case data were derived from ACTIVE, RE-LY, ARISTOTLE, ROCKET-AF, PROTECT-AF and PREVAIL trials. One-way sensitivity analysis varied by CHADS2 score, HAS-BLED score, time horizons, and LAAO costs; and probabilistic sensitivity analysis using 10,000 Monte Carlo simulations was conducted to assess parameter uncertainty. LAAO was considered cost-effective compared with aspirin, clopidogrel plus aspirin, and warfarin, with ICER of US$5,115, $2,447, and $6,298 per QALY gained, respectively. LAAO was dominant (i.e. less costly but more effective) compared to other strategies. Sensitivity analysis demonstrated favorable ICERs of LAAO against other strategies in varied CHADS2 score, HAS-BLED score, time horizons (5 to 15 years) and LAAO costs. LAAO was cost-effective in 86.24 % of 10,000 simulations using a threshold of US$50,000/QALY. Transcatheter LAAO is cost-effective for prevention of stroke in NVAF compared with 7 pharmacological strategies. The transcatheter left atrial appendage occlusion (LAAO) is considered cost-effective against the standard 7 oral pharmacological strategies including acetylsalicylic acid (ASA) alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban for stroke prophylaxis in non-valvular atrial fibrillation management.

  14. Preemptive analgesia I: physiological pathways and pharmacological modalities.

    LENUS (Irish Health Repository)

    Kelly, D J

    2012-02-03

    PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.

  15. Techniques for calculations with nPI effective actions

    Directory of Open Access Journals (Sweden)

    Carrington M.E.

    2015-01-01

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

  16. Spatio-temporal dynamics of action-effect associations in oculomotor control.

    Science.gov (United States)

    Riechelmann, Eva; Pieczykolan, Aleksandra; Horstmann, Gernot; Herwig, Arvid; Huestegge, Lynn

    2017-10-01

    While there is ample evidence that actions are guided by anticipating their effects (ideomotor control) in the manual domain, much less is known about the underlying characteristics and dynamics of effect-based oculomotor control. Here, we address three open issues. 1) Is action-effect anticipation in oculomotor control reflected in corresponding spatial saccade characteristics in inanimate environments? 2) Does the previously reported dependency of action latency on the temporal effect delay (action-effect interval) also occur in the oculomotor domain? 3) Which temporal effect delay is optimally suited to develop strong action-effect associations over time in the oculomotor domain? Participants executed left or right free-choice saccades to peripheral traffic lights, causing an (immediate or delayed) action-contingent light switch in the upper vs. lower part of the traffic light. Results indicated that saccades were spatially shifted toward the location of the upcoming change, indicating anticipation of the effect (location). Saccade latency was affected by effect delay, suggesting that corresponding time information is integrated into event representations. Finally, delayed (vs. immediate) effects were more effective in strengthening action-effect associations over the course of the experiment, likely due to greater saliency of perceptual changes occurring during target fixation as opposed to changes during saccades (saccadic suppression). Overall, basic principles underlying ideomotor control appear to generalize to the oculomotor domain. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

    Science.gov (United States)

    Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

    2015-01-01

    In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

  18. Evaluating pharmacological models of high and low anxiety in sheep

    Directory of Open Access Journals (Sweden)

    Rebecca E. Doyle

    2015-12-01

    Full Text Available New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenylpiperazine (mCPP; 1 mg/kg; n = 12, an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12, or acted as a control (saline intramuscular injection n = 11. Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a ‘runway task’ (moving down a raceway for a food reward, response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001, a greater startle response (1.4 vs. 0.6; p = 0.02, a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001, and a lower feeding motivation (1.8 × slower; p < 0.001 than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of

  19. Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels.

    Science.gov (United States)

    Rossier, Michel F; Pagano, Sabrina; Python, Magaly; Maturana, Andres D; James, Richard W; Mach, François; Roux-Lombard, Pascale; Vuilleumier, Nicolas

    2012-03-01

    Autoantibodies to apolipoprotein A-1 (antiapoA-1 IgG) have been shown to be associated with higher resting heart rate and morbidity in myocardial infarction patients and to behave as a chronotropic agent in the presence of aldosterone on isolated neonatal rat ventricular cardiomyocytes (NRVC). We aimed at identifying the pathways accounting for this aldosterone-dependent antiapoA-1 IgG-positive chronotropic effect on NRVC. The rate of regular spontaneous contractions was determined on NRVC in the presence of different steroid hormones and antagonists. AntiapoA-1 IgG chronotropic response was maximal within 20 min and observed only in aldosterone-pretreated cells but not in those exposed to other steroids. The positive antiapoA-1 IgG chronotropic effect was already significant after 5 min aldosterone preincubation, was dependent on 3-kinase and protein kinase A activities, was not inhibited by actinomycin D, and was fully abrogated by eplerenone (but not by spironolactone), demonstrating the dependence on a nongenomic action of aldosterone elicited through the mineralocorticoid receptor (MR). Under oxidative conditions (but not under normal redox state), corticosterone mimicked the permissive action of aldosterone on the antiapoA-1 IgG chronotropic response. Pharmacological and patch-clamp studies identified L-type calcium channels as crucial effectors of antiapoA-1 IgG chronotropic action, involving two converging pathways that increase the channel activity. The first one involves the rapid, nongenomic activation of the phosphatidylinositol 3-kinase enzyme by MR, and the second one requires a constitutive basal protein kinase A activity. In conclusion, our results indicate that, on NRVC, the aldosterone-dependent chronotropic effects of antiapoA-1 IgG involve the nongenomic activation of L-type calcium channels.

  20. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    André Russowsky Brunoni

    Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention

  1. Simulation in an Undergraduate Nursing Pharmacology Course: A Pilot Study.

    Science.gov (United States)

    Tinnon, Elizabeth; Newton, Rebecca

    This study examined the effectiveness of simulation as a method of teaching pharmacological concepts to nursing students; perceptions of satisfaction with simulation as a teaching strategy were also evaluated. Second-semester juniors participated in three simulations and completed the National League for Nursing Student Satisfaction and Self-Confidence in Learning Questionnaire and the Student Evaluation of Educational Quality Survey; a control group received traditional lectures. A unit exam on anticoagulant therapy content was administered to measure effectiveness. Findings support that simulation is as effective as traditional lecture for an undergraduate pharmacology course.

  2. David J. Triggle: Medicinal chemistry, to pharmacology, calcium channels, and beyond.

    Science.gov (United States)

    Walker, Michael J A

    2015-11-15

    David Triggle's scientific career began as a chemist, went through medicinal chemistry into pharmacology, and finally on to somewhat more philosophical interests in later years. It was a career marked by many contributions to all of those aspects of science. Chief amongst his many contributions, in addition to those in medicinal chemistry, was his work on the drugs known as calcium ion channel blockers or (calcium antagonists). In the calcium ion channel field he was a particularly instrumental figure in sorting out the mechanisms, actions and roles of the class of calcium channel blockers, known chemical and pharmacologically as the dihydropyridines (DHPs) in particular, as well as other calcium blockers of diverse structures. During the course of a long career, and extensive journeys into medicinal chemistry and pharmacology, he published voluminously in terms of papers, reviews, conference proceedings and books. Notably, many of his papers often had limited authorship where, as senior author it reflected his deep involvement in all aspects of the reported work. His work always helped clarify the field while his incisive reviews, together with his role in coordinating and running scientific meetings, were a great help in clarifying and organizing various fields of study. He has had a long and illustrious career, and is wellknown in the world of biomedical science; his contributions are appreciated, and well recognized everywhere. The following article attempts to chart a path through his work and contributions to medicinal chemistry, pharmacology, science, academia and students. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

    Directory of Open Access Journals (Sweden)

    John D. Chan

    2016-12-01

    Full Text Available 5-hydroxytryptamine (5-HT is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL, prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products – nuciferine, D-glaucine, boldine and bulbocapnine – were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages.

  4. Fuzzy pharmacology: theory and applications.

    Science.gov (United States)

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

    2002-09-01

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

  5. 17 CFR 9.12 - Effective date of disciplinary or access denial action.

    Science.gov (United States)

    2010-04-01

    ... ACTIONS Notice and Effective Date of Disciplinary Action or Access Denial Action § 9.12 Effective date of disciplinary or access denial action. (a) Effective date. Any disciplinary or access denial action taken by an... cause a disciplinary action to become effective prior to that time if: (1) As authorized by § 8.25 of...

  6. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

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

  7. Automated tool for virtual screening and pharmacology-based pathway prediction and analysis

    Directory of Open Access Journals (Sweden)

    Sugandh Kumar

    2017-10-01

    Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.

  8. Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

    Science.gov (United States)

    Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

    2010-01-01

    For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.

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

    Directory of Open Access Journals (Sweden)

    Luiza R. Nazario

    2017-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. PHARMACOLOGICAL AND THERAPEUTIC EFFECTS OF JASMINUM SAMBAC- A REVIEW

    OpenAIRE

    Ali Esmail Al-Snafi

    2018-01-01

    The phytochemical analysis of Jasminum sambac revealed the presence of carbohydrates, proteins, amino acids, coumarins, glycosides, tannins, phenolic compounds, flavonoids, phenolics, saponins, steroids, fats, essential oils, fixed oils, terpines, resin, and salicylic acid. The pharmacological studies revealed that the plant extracts possessed antimicrobial, insecticidal, analgesic, antipyretic, antiinflammatory, antioxidant, antidiabetic, dermatological, anticancer, CNS and peripheral NS, ca...

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

    Directory of Open Access Journals (Sweden)

    Yu. G. Levina

    2014-01-01

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

  13. One-Loop Effective Action in Orbifold Compactifications

    CERN Document Server

    Von Gersdorff, Gero

    2008-01-01

    We employ the covariant background formalism to derive generic expressions for the one-loop effective action in field theoretic orbifold compactifications. The contribution of each orbifold sector is given by the effective action of its fixed torus with a shifted mass matrix. We thus study in detail the computation of the heat kernel on tori. Our formalism manifestly separates UV sensitive (local) from UV-insensitive (nonlocal) renormalization. To exemplify our methods, we study the effective potential of 6d gauge theory as well as kinetic terms for gravitational moduli in 11d supergravity.

  14. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

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

  15. The pharmacology of regenerative medicine.

    Science.gov (United States)

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

    2013-07-01

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

  16. Pharmacological Interventions for Students with ADD.

    Science.gov (United States)

    Austin, Vance L.

    2003-01-01

    A review of the research on pharmacological interventions for students with attention deficit disorder finds that psychostimulants such as methylphenidate (Ritalin) are effective in improving focus and impulse control, but should be used in conjunction with psychosocial and behavioral interventions. Comprehensive medical screenings and guidelines…

  17. Pharmacological evaluation of bee venom and melittin

    Directory of Open Access Journals (Sweden)

    Camila G. Dantas

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  18. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

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

  19. Effectiveness of multi-component non-pharmacologic delirium interventions: A Meta-analysis

    Science.gov (United States)

    Hshieh, Tammy T.; Yue, Jirong; Oh, Esther; Puelle, Margaret; Dowal, Sarah; Travison, Thomas; Inouye, Sharon K.

    2015-01-01

    .26) respectively. Among the higher quality RMTs, length of stay trended −0.33 days shorter (95% CI −1.38–0.72) and odds of institutionalization trended 6% lower (95% CI 0.69–1.30). Conclusions and Relevance Multi-component non-pharmacologic delirium prevention interventions are effective in reducing delirium incidence and preventing falls, with trend towards decreasing length of stay and avoiding institutionalization. Given the current focus on prevention of hospital-based complications and improved cost-effectiveness of care, this meta-analysis supports the use of these interventions to advance acute care for older persons. PMID:25643002

  20. Molecular Mechanism for Various Pharmacological Activities of NSAIDS

    Directory of Open Access Journals (Sweden)

    Tohru Mizushima

    2010-05-01

    Full Text Available The anti-inflammatory action of non-steroidal anti-inflammatory drugs (NSAIDs is mediated through their inhibitory effects on cyclooxygenase (COX activity. On the other hand, NSAID use is often associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. Furthermore, recent epidemiological studies have revealed that prolonged NSAID use reduces the risk of cancer and Alzheimer’s disease (AD and a COX-independent unknown mechanism is suggested to be involved in these activities of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions and anti-tumor and anti-AD activities of NSAIDs. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner. We found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. On the other hand, induction of expression of tight junction-related genes and endoplasmic reticulum chaperones were suggested to be involved in anti-tumor and anti-AD, respectively, activities of NSAIDs. These results suggest that NSAIDs affect expression of various genes in a COX-independent manner, which is involved in various pharmacological activities of NSAIDs.

  1. Phytochemistry, pharmacology and traditional uses of different Epilobium species (Onagraceae): a review.

    Science.gov (United States)

    Granica, Sebastian; Piwowarski, Jakub P; Czerwińska, Monika E; Kiss, Anna K

    2014-10-28

    beneficial effect for this disorder, but the number of in vitro studies is not sufficient and the in vivo studies are not conclusive or too preliminary to draw a final conclusion about the efficacy of Epilobium preparations. More in vitro, in vivo and clinical studies to confirm this mode of action are strongly needed. Epilobium's extracts have also documented antioxidative and potential anti-inflammatory properties. Oenothein B can be considered as responsible for some of Epilobium pharmacological properties. Because of the lack of clinical data further studies are needed to provide an evidence base for traditional uses of plant materials belonging to the Epilobium genus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Correlation of pharmacological activity and receptor binding of guanabenz during development

    International Nuclear Information System (INIS)

    Zoltoski, R.K.

    1989-01-01

    Many studies to elucidate the pharmacokinetic, pharmacodynamic, and molecular pharmacological profile of guanabenz, an α 2 -adrenergic receptor agonist, have been reported; however, the effects of this drug on the developing fetus have been largely ignored. The ability of a drug to alter fetal cardiovascular activity is dependent upon both the penetration of the drug across the placenta and upon maturation of the system(s) through which the drug exerts its effects. Consequently, it is hypothesized that the pharmacological activity of guanabenz on the fetus is influenced both by placenta actions on drug transfer and the time course of development of the central and/or peripheral α 2 adrenergic receptor system(s) through which the drug exerts its effects. Guanabenz (GB) when administered to the maternal sheep elicited a cardiovascular response similar to that observed in rats, dogs, and humans. An initial, transient increase in mean arterial pressure (MAP) was followed by a sustained decrease in MAP. This decrease in MAP was accompanied by a prolonged decrease in heart rate (HR). No cardiovascular response to maternally administered GB was observed in the fetal lamb. Pharmacokinetic studies revealed that GB is widely distributed in the pregnant ewe; however, the placenta appears to act as a relative barrier to the transfer of GB into the fetal compartment. In order to ascertain if the mature fetal lamb had developed functional α 2 -adrenergic receptors, GB was administered directly to the fetus. A transient increase in MAP was elicited; however, no prolonged decrease in either MAP or HR occurred. Following validation of [ 3 H]guanabenz ([ 3 H]GB) binding assay in rat cerebral cortex, studies to correlate [ 3 H]GB binding in sheep cortex with pharmacodynamic response was conducted

  3. Pharmacological targeting of Mdm2: Rationale and perspectives for radiosensitization; Ciblage pharmacologique de Mdm2: bases biologiques et perspectives de radiosensibilisation

    Energy Technology Data Exchange (ETDEWEB)

    Chargari, C. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Service d' oncologie radiotherapie, hopital d' instruction des armees du Val-de-Grace, 74, boulevard de Port-Royal, 75230 Paris cedex 5 (France); Leteur, C.; Ferte, C.; Deberne, M.; Lahon, B.; Rivera, C. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Bourhis, J.; Deutsch, E. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, universite Paris-Sud 11, 114, rue edouard-Vaillant, 94805 Villejuif (France)

    2011-07-15

    The central role of p53 after exposure to ionizing radiation has been widely demonstrated. Mdm2, the main cellular regulator of p53, is a promising target for radiosensitizing purposes. In this article, we review the most recent data on the pharmacological targeting of Mdm2, with focus on strategies of radiosensitization. Antitumor activity of Mdm2 inhibitors has been related with activation of p53-dependant apoptosis, action on DNA repair systems, and anti-angiogenic activity. Preliminary data suggested a synergic interaction between Mdm2 inhibitors and ionizing radiations. However, no clinical data has been published yet on the pharmacological targeting of Mdm2. Given their new mechanisms of action, these new molecules should be subject to careful clinical assessment. Although promising, these strategies expose to unexpected toxicities. (authors)

  4. Action-based effects on music perception.

    Science.gov (United States)

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

    2014-01-03

    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.

  5. Action-based effects on music perception

    Science.gov (United States)

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

    2013-01-01

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

  6. Action-based effects on music perception

    Directory of Open Access Journals (Sweden)

    Pieter-Jan eMaes

    2014-01-01

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

  7. Biochemical and pharmacological characterization of irradiated crotamine by gamma rays of {sup 60}Co; Caracterizacao bioquimica e farmacologica da crotamina irradiada por raios gama de {sup 60}Co

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Karina Corleto

    2014-07-01

    The serum production in Brazil, the only effective treatment in cases of snakebites, uses horses that although large size, have reduced l lifespan compared with horses not immunized. Ionizing radiation has been shown as an excellent tool in reducing the toxicity of venoms and toxins isolated, and promote the achievement of better immunogens for serum production, and contributing to the welfare of serum-producing animals. It is known, however, that the effects of ionizing radiation on protein are characterized by various chemical modifications, such as fragmentation, cross-linking due to aggregation and oxidation products generated by water radiolysis. However, the action of gamma radiation on toxins is not yet fully understood structurally and pharmacologically, a fact that prevents the application of this methodology in the serum production process. So we proposed in this paper the characterization of crotamine, an important protein from the venom of Crotalus durissus terrificus species, irradiated with {sup 60}Co gamma rays. After isolating the toxin by chromatographic techniques and testing to prove the obtaining of pure crotamine, it was irradiated with gamma rays and subjected to structural analysis, Fluorescence and Circular Dichroism. Using high hydrostatic pressure tests were also conducted in order to verify that the conformational changes caused by radiation suffer modifications under high pressures. From the pharmacological point of view, muscle contraction tests were conducted with the objective of limiting the action of crotamine in smooth muscle as well as the change in the action of toxin caused structural changes to the front. Analysis of Circular Dichroism and Fluorescence showed changes in structural conformation of crotamine when subjected to gamma radiation and that such changes possibly occurring in the secondary and tertiary structure of the protein. The observed in pharmacological tests showed that the irradiated crotamine was less effective

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

    Science.gov (United States)

    Li, Shuping; Cheng, Xuemei; Wang, Changhong

    2017-05-05

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

  9. Physical Properties and Effect in a Battery of Safety Pharmacology Models for Three Structurally Distinct Enteric Polymers Employed as Spray-dried Dispersion Carriers

    Directory of Open Access Journals (Sweden)

    Ryan M Fryer

    2016-10-01

    Full Text Available Establishing a wide therapeutic index (TI for pre-clinical safety is important during lead optimization (LO in research, prior to clinical development, although is often limited by a molecules physiochemical characteristics. Recent advances in the application of the innovative vibrating mesh spray-drying technology to prepare amorphous solid dispersions may offer an opportunity to achieve high plasma concentrations of poorly soluble NCEs to enable testing and establishment of a wide TI in safety pharmacology studies. While some of the amorphous solid dispersion carriers are generally recognized as safe for clinical use, whether they are sufficiently benign to enable in vivo pharmacology studies has not been sufficiently demonstrated. Thus, the physical properties, and effect in a battery of in vivo safety pharmacology models, were assessed in three classes of polymers employed as spray-dried dispersion carriers. The polymers (HPMC-AS, Eudragit, PVAP displayed low affinity with acetone/methanol, suitable for solvent-based spray drying. The water sorption of the polymers was moderate, and the degree of hysteresis of HPMC-AS was smaller than Eudragit and PVAP indicating the intermolecular interaction of water-cellulose molecules is weaker than water-acrylate or water-polyvinyl molecules. The polymer particles were well-suspended without aggregation with a mean particle size less than 3 µm in an aqueous vehicle. When tested in conscious Wistar Han rats in safety pharmacology models (n=6-8/dose/polymer investigating effects on CNS, gastrointestinal, and cardiovascular function, no liabilities were identified at any dose tested (30-300 mg/kg PO, suspension. In brief, the polymers had no effect in a modified Irwin test that included observational and evoked endpoints related to stereotypies, excitation, sedation, pain/anesthesia, autonomic balance, reflexes, and others. No effect of the polymers on gastric emptying or intestinal transit was observed

  10. Alternative pharmacological treatment options for agitation in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Francesco Panza

    2015-11-01

    Full Text Available In patients with dementia and Alzheimer’s disease (AD, treatment of neuropsychiatric symptoms (NPS is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs, with disappointing results. However, evidence coming from recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/ quinidine, cannabinoids, and citalopram showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia.

  11. Jatropha Tanjorensis - Review of Phytochemistry, Pharmacology ...

    African Journals Online (AJOL)

    Based on the findings of this work, future study on the phytochemistry and chemical constituents in relation to certain other biological activities are required to fully understand the phytochemical and complex pharmacological effect of the plant specie. Further work to isolate active compounds from the plant is also necessary.

  12. When love hurts. A systematic review on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning.

    Science.gov (United States)

    Barbara, Giussy; Facchin, Federica; Meschia, Michele; Berlanda, Nicola; Frattaruolo, Maria P; VercellinI, Paolo

    2017-06-01

    Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning, and to provide suggestions for future treatment strategies. We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided into two categories: (a) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; (b) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. Single dose silodosin prior to voiding cystourethrogram: a pharmacological adjunct to enhance visualization of posterior urethra.

    Science.gov (United States)

    Nagathan, Deepak Sharanappa; Dalela, Divakar; Sankhwar, Satyanarayan; Goel, Apul; Dwivedi, Amod Kumar; Yadav, Rahul

    2014-03-04

    Voiding cystourethrogram (VCUG) is needed to ascertain the upper end of urethral stricture. Occasionally, a patient is unable to open the bladder neck with resultant failure of the test. Realizing the strong and prompt alpha antagonistic action of silodosin, we evaluated single 8 mg dose as a pharmacological adjunct prior to VCUG to overcome this problem.

  14. Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren Hein; Holbech, J.; Demant, Dyveke T

    2017-01-01

    Background: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for...... baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed. Results: Diabetes as etiology...

  15. Background characteristics and treatment-related factors associated with treatment success or failure in a non-pharmacological intervention for dementia caregivers.

    Science.gov (United States)

    Rose, Karen C; Gitlin, Laura N

    2017-06-01

    Non-pharmacological interventions for persons with dementia often rely on family caregivers for implementation. However, caregivers differ in their readiness to use strategies. This study examines dyadic characteristics and treatment-related mechanisms associated with treatment success (high readiness to use strategies) and failure (low readiness to use strategies) at the conclusion of the Advancing Caregiver Training (ACT) intervention. Caregiver and person with dementia characteristics and treatment-related variables (treatment participation, number and type of strategies introduced and enacted) were examined in 110 caregivers in intervention. Interventionists rated readiness (1=precontemplation; 2=contemplation; 3=preparation; 4=action) of caregivers to use strategies at the final ACT session. Univariate analyses examined dyadic characteristics, and Multiple Analysis of Covariance (MANCOVA) and Analyses of Covariance (ANCOVA) examined treatment-related factors associated with readiness to use strategies at treatment completion. At treatment completion, 28.2% (N=31) scored in pre-action and 71.8% (N=79) at action. Caregivers at pre-action readiness levels were more likely than those at action to be a spouse, report greater financial difficulties and be managing fewer problem behaviors. Although both groups were introduced an equivalent number of non-pharmacological strategies, caregivers at pre-action were less likely than those at action to report enacting strategies. Certain dyadic characteristics and treatment-related factors were associated with treatment failure including financial strain and lack of strategy integration. Findings suggest that developing intervention components to address financial concerns and increase opportunities for practicing strategies and then using them between treatment sessions may be important for caregivers at risk of treatment failure.

  16. Covariant effective action for loop quantum cosmology from order reduction

    International Nuclear Information System (INIS)

    Sotiriou, Thomas P.

    2009-01-01

    Loop quantum cosmology (LQC) seems to be predicting modified effective Friedmann equations without extra degrees of freedom. A puzzle arises if one decides to seek for a covariant effective action which would lead to the given Friedmann equation: The Einstein-Hilbert action is the only action that leads to second order field equations and, hence, there exists no covariant action which, under metric variation, leads to a modified Friedmann equation without extra degrees of freedom. It is shown that, at least for isotropic models in LQC, this issue is naturally resolved and a covariant effective action can be found if one considers higher order theories of gravity but faithfully follows effective field theory techniques. However, our analysis also raises doubts on whether a covariant description without background structures can be found for anisotropic models.

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

    Directory of Open Access Journals (Sweden)

    Lynch Tadhg

    2009-04-01

    Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

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

    LENUS (Irish Health Repository)

    Maharaj, Chrisen H

    2009-01-01

    OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

  19. Human Behavioral Pharmacology, Past, Present, and Future: Symposium Presented at the 50th Annual Meeting of the Behavioral Pharmacology Society

    Science.gov (United States)

    Comer, Sandra D.; Bickel, Warren K.; Yi, Richard; de Wit, Harriet; Higgins, Stephen T.; Wenger, Galen R.; Johanson, Chris-Ellyn; Kreek, Mary Jeanne

    2010-01-01

    A symposium held at the 50th annual meeting of the Behavioral Pharmacology Society in May 2007 reviewed progress in the human behavioral pharmacology of drug abuse. Studies on drug self-administration in humans are reviewed that assessed reinforcing and subjective effects of drugs of abuse. The close parallels observed between studies in humans and laboratory animals using similar behavioral techniques have broadened our understanding of the complex nature of the pharmacological and behavioral factors controlling drug self-administration. The symposium also addressed the role that individual differences, such as gender, personality, and genotype play in determining the extent of self-administration of illicit drugs in human populations. Knowledge of how these factors influence human drug self-administration has helped validate similar differences observed in laboratory animals. In recognition that drug self-administration is but one of many choices available in the lives of humans, the symposium addressed the ways in which choice behavior can be studied in humans. These choice studies in human drug abusers have opened up new and exciting avenues of research in laboratory animals. Finally, the symposium reviewed behavioral pharmacology studies conducted in drug abuse treatment settings and the therapeutic benefits that have emerged from these studies. PMID:20664330

  20. Artificial oxygen carrier with pharmacologic actions of adenosine-5'-triphosphate, adenosine, and reduced glutathione formulated to treat an array of medical conditions.

    Science.gov (United States)

    Simoni, Jan; Simoni, Grace; Moeller, John F; Feola, Mario; Wesson, Donald E

    2014-08-01

    Effective artificial oxygen carriers may offer a solution to tackling current transfusion medicine challenges such as blood shortages, red blood cell storage lesions, and transmission of emerging pathogens. These products, could provide additional therapeutic benefits besides oxygen delivery for an array of medical conditions. To meet these needs, we developed a hemoglobin (Hb)-based oxygen carrier, HemoTech, which utilizes the concept of pharmacologic cross-linking. It consists of purified bovine Hb cross-linked intramolecularly with open ring adenosine-5'-triphosphate (ATP) and intermolecularly with open ring adenosine, and conjugated with reduced glutathione (GSH). In this composition, ATP prevents Hb dimerization, and adenosine promotes formation of Hb polymers as well as counteracts the vasoconstrictive and pro-inflammatory properties of Hb via stimulation of adenosine receptors. ATP also serves as a regulator of vascular tone through activation of purinergic receptors. GSH blocks Hb's extravasation and glomerular filtration by lowering the isoelectric point, as well as shields heme from nitric oxide and reactive oxygen species. HemoTech and its manufacturing technology have been broadly tested, including viral and prion clearance validation studies and various nonclinical pharmacology, toxicology, genotoxicity, and efficacy tests. The clinical proof-of-concept was carried out in sickle cell anemia subjects. The preclinical and clinical studies indicate that HemoTech works as a physiologic oxygen carrier and has efficacy in treating: (i) acute blood loss anemia by providing a temporary oxygen bridge while stimulating an endogenous erythropoietic response; (ii) sickle cell disease by counteracting vaso-occlusive/inflammatory episodes and anemia; and (iii) ischemic vascular diseases particularly thrombotic and restenotic events. The pharmacologic cross-linking of Hb with ATP, adenosine, and GSH showed usefulness in designing an artificial oxygen carrier for

  1. Exploring soft constraints on effective actions

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Massimo; Guerrieri, Andrea L. [Dipartimento di Fisica, Università di Roma “Tor Vergata”,I.N.F.N. Sezione di Roma “Tor Vergata”,Via della Ricerca Scientifica, Roma, 00133 (Italy); Huang, Yu-tin; Lee, Chao-Jung [Department of Physics and Astronomy, National Taiwan University,No. 1 Roosevelt Road Sec. 4, Taipei, Taiwan (China); Wen, Congkao [Dipartimento di Fisica, Università di Roma “Tor Vergata”,I.N.F.N. Sezione di Roma “Tor Vergata”,Via della Ricerca Scientifica, Roma, 00133 (Italy)

    2016-10-10

    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 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{sup n}∼∂{sup 2n} are completely determined in terms of the k-point amplitudes at order s{sup k} with k≤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 particular, the effective action is fixed up to eight derivatives in terms of just one unknown four-point coefficient and one more coefficient for ten-derivative terms. Finally, we also study the interplay between scale and conformal invariance in this context.

  2. Nonlocal quantum effective actions in Weyl-Flat spacetimes

    Science.gov (United States)

    Bautista, Teresa; Benevides, André; Dabholkar, Atish

    2018-06-01

    Virtual massless particles in quantum loops lead to nonlocal effects which can have interesting consequences, for example, for primordial magnetogenesis in cosmology or for computing finite N corrections in holography. We describe how the quantum effective actions summarizing these effects can be computed efficiently for Weyl-flat metrics by integrating the Weyl anomaly or, equivalently, the local renormalization group equation. This method relies only on the local Schwinger-DeWitt expansion of the heat kernel and allows for a re-summation of the anomalous leading large logarithms of the scale factor, log a( x), in situations where the Weyl factor changes by several e-foldings. As an illustration, we obtain the quantum effective action for the Yang-Mills field coupled to massless matter, and the self-interacting massless scalar field. Our action reduces to the nonlocal action obtained using the Barvinsky-Vilkovisky covariant perturbation theory in the regime R 2 ≪ ∇2 R for a typical curvature scale R, but has a greater range of validity effectively re-summing the covariant perturbation theory to all orders in curvatures. In particular, it is applicable also in the opposite regime R 2 ≫ ∇2 R, which is often of interest in cosmology.

  3. Convergence and divergence, a concept for explaining drug actions.

    Science.gov (United States)

    Watanabe, Takehiko; Kamisaki, Yoshinori; Timmerman, Henk

    2004-10-01

    For the teaching and/or learning about drug actions and for the discovery and development of new drugs, it is important to understand how drugs act on living bodies. So far, there has been no clear description on the general principle of drug action in pharmacology textbooks. We propose two principles to depict the action mechanism of drugs. The first is that most, if not all, drugs act on proteins at the molecular level, that is, enzymes, receptors, ion channels, and transporters. The second is that a drug may cause divergent or convergent responses, resulting in changes of a physiological or pathological function of the human body. The concept of divergence and convergence can be used to explain the complex individuality of drug actions.

  4. Effective action in multidimensional quantum gravity and spontaneous compactification

    International Nuclear Information System (INIS)

    Bagrov, V.G.; Bukhbinder, I.L.; Odintsov, S.D.

    1987-01-01

    One-loop effective action (the Casimir energy) is obtained for a special model of multidimensional quantum gravity and several variants of the d-dimensional quantum R 2 gravity in the space M 4 xT d-4 , where M 4 is the Minkowski space and T d-4 is the (d-4)-dimensional torus. It is shown that the effective action for the conformal gravity and the R 2 gravity without cosmological and Einstein's terms lead to an instability of the classical compactification. A numerical calculation reveals that the effective action for the five-dimensional R 2 gravity with the cosmological term is compatible with a self-consistent spontaneous compactification. The one-loop effective action is also obtained for the five dimensional Einstein gravity with the antisymmetrical torsion in the space M 4 xS 1 , where S 1 is the one-dimensional sphere

  5. Effective action in multidimensional quantum gravity, and spontaneous compactification

    International Nuclear Information System (INIS)

    Bagrov, V.G.; Bukhbinder, I.L.; Odintsov, S.D.

    1987-01-01

    The one-loop effective action (Casimir energy) is obtained for a special form of model of multidimensional quantum gravity and for several variants of d-dimensional quantum R 2 -gravity on the space M 4 x T/sub d//sub -4/, where M 4 is Minkowski space and T/sub d//sub -4/ is the (d-4)-dimensional torus. It is shown that the effective action of the model of multidimensional quantum gravity and R 2 -gravity without the cosmological term and Einstein term leads to instability of the classical compactification. By a numerical calculation it is demonstrated that the effective action of five-dimensional R 2 -gravity with the cosmological term admits a self-consistent spontaneous compactification. The one-loop effective action is also found for five-dimensional Einstein gravity with antisymmetric torsion on the space M 4 x S 1 (S 1 is the one-dimensional sphere)

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

    Science.gov (United States)

    Ford, Andrew H; Almeida, Osvaldo P

    2017-02-01

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

  7. [The effect of finoptin on the metabolism and pharmacological action of cyclophosphane in vivo and in vitro].

    Science.gov (United States)

    Donenko, F V; Chikvashvili, B Sh; Borovkova, N B; Devichenskiĭ, V M; Kabieva, A O; Korneva, E N; Telegin, L Iu; Shcherbakov, V M; Letiagin, V P; Moroz, L V

    1991-03-01

    Phynoptin (Ph) and cyclophosphamide (CP) gave rise to a type I spectral changes with liver microsomal fraction. KS were 15 microM and 2150 microM, respectively. Ph increases the concentration of NBP product(s) of CP and acrolein in the blood plasma of animals. Ph increases a toxicity of CP. LD50 was 388.0 +/- 13.9 mg/kg for CP and LD50 was 342.8 +/- 16.9 mg/kg for CP in combination with Ph. Ph changes a therapeutic action of CP in mice with hemocytoblastosis La. Pharmacokinetic interactions have been demonstrated between calcium antagonists Ph and CP.

  8. Pharmacological enhancement of treatment for amblyopia

    Science.gov (United States)

    Rashad, Mohammad A

    2012-01-01

    Background The purpose of this study was to compare a weight-adjusted dose of carbidopa- levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia. Methods This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks. Results The mean logarithm of the minimal angle of resolution (logMAR) of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51) than in the pharmacological enhancement group (0.58, 0.49, and 0.56) at three follow-up visits (at months 1, 3, and 12, respectively). There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51) and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56) at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively). The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5%) than in the occlusion group (30%). The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3%) than in the occlusion group (22%). Conclusion Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add to the effect of occlusion in severe amblyopia and bilateral amblyopia. PMID:22536029

  9. Radioimmunoassay in basic and clinical pharmacology

    International Nuclear Information System (INIS)

    Patrono, C.; Peskar, B.A.

    1987-01-01

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

  10. Effect of pharmacological interventions on the fronto-cingulo-parietal cognitive control network in psychiatric disorders: a transdiagnostic systematic review of fMRI studies

    Directory of Open Access Journals (Sweden)

    Therese eVan Amelsvoort

    2016-05-01

    Full Text Available Executive function deficits such as working memory, decision-making, and attention problems are a common feature of several psychiatric disorders for which no satisfactory treatment exists. Here, we transdiagnostically investigate the effects of pharmacological interventions (other than methylphenidate on the fronto-cingulo-parietal cognitive control network, in order to identify functional brain markers for future pro-cognitive pharmacological interventions. 29 manuscripts investigated the effect of pharmacological treatment on executive function-related brain correlates in psychotic disorders (n=11, depression (n=4, bipolar disorder (n=4, ADHD (n=4, OCD (n=2, smoking dependence (n=2, alcohol dependence (n=1 and pathological gambling (n=1. In terms of impact on the fronto-cingulo-parietal networks, the preliminary evidence for catechol-o-methyl-transferase inhibitors, nicotinic receptor agonists and atomoxetine suggested was relatively consistent, the data for atypical antipsychotics and anticonvulsants moderate, and interpretation of the data for antidepressants was hampered by the employed study designs. Increased activity in task-relevant areas and decreased activity in task-irrelevant areas were the most common transdiagnostic effects of pharmacological treatment. These markers showed good positive and moderate negative predictive value. It is concluded that fronto-cingulo-parietal activity changes can serve as a marker for future pro-cognitive interventions. Future recommendations include the use of randomized double-blind designs and selective cholinergic and glutamatergic compounds.

  11. Amino acid neurotransmitters and new approaches to anticonvulsant drug action.

    Science.gov (United States)

    Meldrum, B

    1984-01-01

    Amino acids provide the most universal and important inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate, cysteic acid, cysteine sulphinic acid) neurotransmitters in the brain. An anticonvulsant action may be produced (1) by enhancing inhibitory (GABAergic) processes, and (2) by diminishing excitatory transmission. Possible pharmacological mechanisms for enhancing GABA-mediated inhibition include (1) GABA agonist action, (2) GABA prodrugs, (3) drugs facilitating GABA release from terminals, (4) inhibition of GABA-transaminase, (5) allosteric enhancement of the efficacy of GABA at the receptor complex, (6) direction action on the chloride ionophore, and (7) inhibition of GABA reuptake. Examples of these approaches include the use of irreversible GABA-transaminase inhibitors, such as gamma-vinyl GABA, and the development of anticonvulsant beta-carbolines that interact with the "benzodiazepine receptor." Pharmacological mechanisms for diminishing excitatory transmission include (1) enzyme inhibitors that decrease the maximal rate of synthesis of glutamate or aspartate, (2) drugs that decrease the synaptic release of glutamate or aspartate, and (3) drugs that block the post-synaptic action of excitatory amino acids. Compounds that selectively antagonise excitation due to dicarboxylic amino acids have recently been developed. Those that selectively block excitation produced by N-methyl-D-aspartate (and aspartate) have proved to be potent anticonvulsants in many animal models of epilepsy. This provides a novel approach to the design of anticonvulsant drugs.

  12. Nonlocal effective actions in semiclassical gravity: Thermal effects in stationary geometries

    Science.gov (United States)

    Elías, M.; Mazzitelli, F. D.; Trombetta, L. G.

    2017-11-01

    We compute the gravitational effective action by integrating out quantum matter fields in a weak gravitational field, using the Schwinger-Keldysh (in-in) formalism. We pay particular attention to the role of the initial quantum state in the structure of the nonlocal terms in the effective action, with an eye to nonlinear completions of the theory that may be relevant in astrophysics and cosmology. In this first paper we consider a quantum scalar field in thermal equilibrium, in a stationary gravitational field. We obtain a covariant expression for the nonlocal effective action, which can be expressed in terms of the curvature tensor, the four-velocity of the thermal bath, and the local Tolman temperature. We discuss the connection between the results for ultrastatic and static metrics through conformal transformations, and the main features of the thermal corrections to the semiclassical Einstein equations.

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

    Directory of Open Access Journals (Sweden)

    Paul Simon Muhle-Karbe

    2012-11-01

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

  14. Wong's equations and the small x effective action in QCD

    International Nuclear Information System (INIS)

    Jalilian-Marian, Jamal; Jeon, Sangyong; Venugopalan, Raju

    2001-01-01

    We propose a new form for the small x effective action in QCD. This form of the effective action is motivated by Wong's equations for classical, colored particles in non-Abelian background fields. We show that the BFKL equation, which sums leading logarithms in x, is efficiently reproduced with this form of the action. We argue that this form of the action may be particularly useful in computing next-to-leading-order results in QCD at small x

  15. Wong's equations and the small x effective action in QCD

    International Nuclear Information System (INIS)

    Jalilian-Marian, Jamal; Jeon, Sangyong; Venugopalan, Raju

    2000-01-01

    We propose a new form for the small x effective action in QCD. This form of the effective action is motivated by Wong's equations for classical, colored particles in non-Abelian background fields. We show that the BFKL equation, which sums leading logarithms in x, is efficiently reproduced with this form of the action. We argue that this form of the action may be particularly useful in computing next-to-leading-order results in QCD at small x

  16. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  17. Melastoma malabathricum (L. Smith Ethnomedicinal Uses, Chemical Constituents, and Pharmacological Properties: A Review

    Directory of Open Access Journals (Sweden)

    S. Mohd. Joffry

    2012-01-01

    Full Text Available Melastoma malabathricum L. (Melastomataceae is one of the 22 species found in the Southeast Asian region, including Malaysia. Considered as native to tropical and temperate Asia and the Pacific Islands, this commonly found small shrub has gained herbal status in the Malay folklore belief as well as the Indian, Chinese, and Indonesian folk medicines. Ethnopharmacologically, the leaves, shoots, barks, seeds, and roots of M. malabathricum have been used to treat diarrhoea, dysentery, hemorrhoids, cuts and wounds, toothache, and stomachache. Scientific findings also revealed the wide pharmacological actions of various parts of M. malabthricum, such as antinociceptive, anti-inflammatory, wound healing, antidiarrheal, cytotoxic, and antioxidant activities. Various types of phytochemical constituents have also been isolated and identifed from different parts of M. malabathricum. Thus, the aim of the present review is to present comprehensive information on ethnomedicinal uses, phytochemical constituents, and pharmacological activities of M. malabathricum.

  18. Interprofessional education in pharmacology using high-fidelity simulation.

    Science.gov (United States)

    Meyer, Brittney A; Seefeldt, Teresa M; Ngorsuraches, Surachat; Hendrickx, Lori D; Lubeck, Paula M; Farver, Debra K; Heins, Jodi R

    2017-11-01

    This study examined the feasibility of an interprofessional high-fidelity pharmacology simulation and its impact on pharmacy and nursing students' perceptions of interprofessionalism and pharmacology knowledge. Pharmacy and nursing students participated in a pharmacology simulation using a high-fidelity patient simulator. Faculty-facilitated debriefing included discussion of the case and collaboration. To determine the impact of the activity on students' perceptions of interprofessionalism and their ability to apply pharmacology knowledge, surveys were administered to students before and after the simulation. Attitudes Toward Health Care Teams scale (ATHCT) scores improved from 4.55 to 4.72 on a scale of 1-6 (p = 0.005). Almost all (over 90%) of the students stated their pharmacology knowledge and their ability to apply that knowledge improved following the simulation. A simulation in pharmacology is feasible and favorably affected students' interprofessionalism and pharmacology knowledge perceptions. Pharmacology is a core science course required by multiple health professions in early program curricula, making it favorable for incorporation of interprofessional learning experiences. However, reports of high-fidelity interprofessional simulation in pharmacology courses are limited. This manuscript contributes to the literature in the field of interprofessional education by demonstrating that an interprofessional simulation in pharmacology is feasible and can favorably affect students' perceptions of interprofessionalism. This manuscript provides an example of a pharmacology interprofessional simulation that faculty in other programs can use to build similar educational activities. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

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

    2011-01-01

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

  20. Imaging tools to study pharmacology: functional MRI on small rodents

    Directory of Open Access Journals (Sweden)

    Elisabeth eJonckers

    2015-10-01

    Full Text Available Functional Magnetic Resonance Imaging (fMRI is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD fMRI techniques, including resting state (rsfMRI, stimulus-evoked (st-fMRI, and pharmacological MRI (phMRI. Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anaesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically-induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest (ROIs. In addition, fMRI techniques allow one to dissect how specific modifications (e.g. treatment, lesion etc. modulate the functioning of specific brain areas (st-fMRI, phMRI and how functional connectivity (rsfMRI between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with

  1. Pharmacological stress agents in nuclear cardiology

    International Nuclear Information System (INIS)

    Buscombe, J.R.

    2004-01-01

    Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. However there are a group of patients who may not be able to undergo treadmill tests. Patients with underlying conditions like neuromuscular disease, musculoskeletal disorder, heart failure and end-stage renal disease (ESRD) on renal dialysis would find it difficult to perform exercise on a treadmill or bicycle ergometer. These conditions prevent them from performing adequate exercise. Such patients would benefit from pharmacological stress procedures combined with MPS. Nuclear medicine departments use various pharmacological agents while performing stress tests on cardiac patients. The most commonly used pharmacological agents for cardiac stress are coronary vasodilators and catecholamines. In addition to these agents, adjuvant use of nitrates and atropine is also a common practice in nuclear cardiology. This review addresses various physiological and pharmacological properties of the commonly used pharmacological stress agents in MPS and critically analyses their advantages and disadvantages, as well as their safety and efficacy. (author)

  2. Response selection difficulty modulates the behavioral impact of rapidly learnt action effects.

    Directory of Open Access Journals (Sweden)

    Uta eWolfensteller

    2014-12-01

    Full Text Available It is well established that we can pick up action effect associations when acting in a free-choice intentional mode. However, it is less clear whether and when action effect associations are learnt and actually affect behavior if we are acting in a forced-choice mode, applying a specific stimulus-response (S-R rule. In the present study, we investigated whether response selection difficulty imposed by S-R rules influences the initial rapid learning and the behavioral expression of previously learnt but weakly practiced action effect associations when those are re-activated by effect exposure. Experiment 1 showed that the rapid acquisition of action effect associations is not directly influenced by response selection difficulty. By contrast, the behavioral expression of re-activated action effect associations is prevented when actions are directly activated by highly over-learnt response cues and thus response selection difficulty is low. However, all three experiments showed that if response selection difficulty is sufficiently high during re-activation, the same action effect associations do influence behavior. Experiment 2 and 3 revealed that the effect of response selection difficulty cannot be fully reduced to giving action effects more time to prime an action, but seems to reflect competition during response selection. Finally, the present data suggest that when multiple novel rules are rapidly learnt in succession, which requires a lot of flexibility, action effect associations continue to influence behavior only if response selection difficulty is sufficiently high. Thus, response selection difficulty might modulate the impact of experiencing multiple learning episodes on action effect expression and learning, possibly via inducing different strategies.

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

    Science.gov (United States)

    Hung, Hsuan-Man; Chiang, Hsiao-Ching

    2017-02-01

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

  4. Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology.

    Science.gov (United States)

    Yang, Fude; Dong, Xiaoxv; Yin, Xingbin; Wang, Wenping; You, Longtai; Ni, Jian

    2017-01-01

    Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b 2 , c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri . This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.

  5. Pharmacological Activity and Clinical Use of PDRN

    Science.gov (United States)

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

    2017-01-01

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

  6. Internet discussion forums as part of a student-centred teaching concept of pharmacology.

    Science.gov (United States)

    Sucha, Michael; Engelhardt, Stefan; Sarikas, Antonio

    2013-01-01

    The world wide web opens up new opportunities to interconnect electronic and classroom teaching and to promote active student participation. In this project article we describe the use of internet discussion forums as part of a student-centred teaching concept of pharmacology and discuss its advantages and disadvantages based on evaluation data and current literature. Final year medical students at the Technische Universität München (Munich, Germany) with the elective pharmacology moderated an internet forum that allowed all students to discuss pharmacology-related questions. Evaluation results of forum participants and elective students demonstrated a learning benefit of internet forums in pharmacology teaching. Internet discussion forums offer an easy-to-implement and effective way to actively engage students and increase the learning benefit of electronic and classroom teaching in pharmacology.

  7. Imaging tools to study pharmacology: functional MRI on small rodents

    OpenAIRE

    Elisabeth eJonckers; Disha eShah; Julie eHamaide; Marleen eVerhoye; Annemie eVan Der Linden

    2015-01-01

    Functional Magnetic Resonance Imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimu...

  8. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

    Science.gov (United States)

    Aznar, Susana; Klein, Anders B

    2013-12-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  9. [Modern research progress of traditional Chinese medicine based on integrative pharmacology].

    Science.gov (United States)

    Wang, Ping; Tang, Shi-Huan; Su, Jin; Zhang, Jia-Qi; Cui, Ru-Yi; Xu, Hai-Yu; Yang, Hong-Jun

    2018-04-01

    Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " in vivo and in vitro ", " in vivo process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP. Copyright© by the Chinese Pharmaceutical Association.

  10. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  11. Pharmacological treatment of sleep disorders and its relationship with neuroplasticity.

    Science.gov (United States)

    Abad, Vivien C; Guilleminault, Christian

    2015-01-01

    Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

  12. Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application

    OpenAIRE

    Zhao, Pan; Sui, Bing‐Dong; Liu, Nu; Lv, Ya‐Jie; Zheng, Chen‐Xi; Lu, Yong‐Bo; Huang, Wen‐Tao; Zhou, Cui‐Hong; Chen, Ji; Pang, Dan‐Lin; Fei, Dong‐Dong; Xuan, Kun; Hu, Cheng‐Hu; Jin, Yan

    2017-01-01

    Summary Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical ad...

  13. High-energy effective action from scattering of QCD shock waves

    Energy Technology Data Exchange (ETDEWEB)

    Ian Balitsky

    2005-07-01

    At high energies, the relevant degrees of freedom are Wilson lines - infinite gauge links ordered along straight lines collinear to the velocities of colliding particles. The effective action for these Wilson lines is determined by the scattering of QCD shock waves. I develop the symmetric expansion of the effective action in powers of strength of one of the shock waves and calculate the leading term of the series. The corresponding first-order effective action, symmetric with respect to projectile and target, includes both up and down fan diagrams and pomeron loops.

  14. Integrated quantitative pharmacology for treatment optimization in oncology

    NARCIS (Netherlands)

    Hasselt, J.G.C. van

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-12-16

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

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

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

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

  17. Pharmacological enhancement of treatment for amblyopia

    Directory of Open Access Journals (Sweden)

    Rashad MA

    2012-03-01

    Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptBackground: The purpose of this study was to compare a weight-adjusted dose of carbidopa-levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia.Methods: This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks.Results: The mean logarithm of the minimal angle of resolution (logMAR of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51 than in the pharmacological enhancement group (0.58, 0.49, and 0.56 at three follow-up visits (at months 1, 3, and 12, respectively. There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51 and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56 at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively. The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5% than in the occlusion group (30%. The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3% than in the occlusion group (22%.Conclusion: Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add

  18. The role of objects and effects in action imitation: Comparing the imitation of object-related actions vs. gestures in 18-month-old infants.

    Science.gov (United States)

    Kim, Ziyon; Óturai, Gabriella; Király, Ildikó; Knopf, Monika

    2015-11-01

    This study aimed to systematically investigate 18-month-old infants' imitation of object-related actions compared to motorically similar gestures. An additional goal of the study was to examine the role of action effects on infants' imitation of target actions. One group of infants (n=17) observed object-related actions and gestures leading to salient effects (sounds or visual resp. social effects), and the other group (n=16) watched the same actions without effects. Furthermore, this study examined whether infants show a consistent imitation ability for object-related actions and gestures. First, the present study showed that 18-month-old infants imitated object-related actions more frequently than gestures. Second, the presence of an effect significantly increased the imitation rate of object-related actions; however, this difference was not found for gestures. Third, indications for a general imitation ability were found as results on an individual level showed that object-related action imitation significantly correlated with gesture imitation. Implications of the results for theory and future studies are discussed with a focus on the role of objects and effects in 18-month-old infants' action imitation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 2011 Annual Meeting of the Safety Pharmacology Society: an overview.

    Science.gov (United States)

    Cavero, Icilio

    2012-03-01

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

  20. The pharmacological assay as a tool to medicinal plants domestication

    Directory of Open Access Journals (Sweden)

    Montanari Jr., Ilio

    2016-07-01

    Full Text Available In Brazil studies with native medicinal plants are usually performed using non-domesticated plants and as a result the genetic variability of wild species could express different levels of active principles changing their therapeutic effect. Based on that, the aim of this study was to demonstrate that extract of different half- sib families Cordia verbenacea (DC, widely used as medicinal plant in Brazil, have different efficacy in the Total Growth Inhibition (TGI of 5 different human tumor cell lines. Data were statistically analyzed using ANOVA follow by Tuckey test and a heritability estimation of the plant families was performed. The results showed that TGI are different for each plant family according with each human tumor cell line. For instance, extracts obtained from families 3,11 and 12 were more effective to inhibit the U-251 and Ht-29 cell lines compared to the other families, while extracts obtained from the family 32 was more effective against thethe PC-3 line. The heritability coefficient indicated that plant population selection could promote a genetic improvement related to its active principle and their pharmacological effect and could provide the identification of the best families according to their pharmacological efficacy. In conclusion, this study suggests that the domestication of a wild medicinal plant should be better monitored by its pharmacological effect.

  1. [Contribution of animal experimentation to pharmacology].

    Science.gov (United States)

    Sassard, Jean; Hamon, Michel; Galibert, Francis

    2009-11-01

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

  2. In vitro and in vivo pharmacological characterization of a neuropeptide S tetrabranched derivative.

    Science.gov (United States)

    Ruzza, Chiara; Rizzi, Anna; Malfacini, Davide; Pulga, Alice; Pacifico, Salvatore; Salvadori, Severo; Trapella, Claudio; Reinscheid, Rainer K; Calo, Girolamo; Guerrini, Remo

    2015-02-01

    The peptide welding technology (PWT) is a novel chemical strategy that allows the synthesis of multibranched peptides with high yield, purity, and reproducibility. With this approach, a tetrabranched derivative of neuropeptide S (NPS) has been synthesized and pharmacologically characterized. The in vitro activity of PWT1-NPS has been studied in a calcium mobilization assay. In vivo, PWT1-NPS has been investigated in the locomotor activity (LA) and recovery of the righting reflex (RR) tests. In calcium mobilization studies, PWT1-NPS behaved as full agonist at the mouse NPS receptor (NPSR) being threefold more potent than NPS. The selective NPSR antagonists [ (t) Bu-D-Gly(5)]NPS and SHA 68 displayed similar potency values against NPS and PWT1-NPS. In vivo, both NPS (1-100 pmol, i.c.v.) and PWT1-NPS (0.1-100 pmol, i.c.v.) stimulated mouse LA, with PWT1-NPS showing higher potency than NPS. In the RR assay, NPS (100 pmol, i.c.v.) was able to reduce the percentage of mice losing the RR after diazepam administration and their sleep time 5 min after the i.c.v. injection, but it was totally inactive 2 h after the injection. On the contrary, PWT1-NPS (30 pmol, i.c.v.), injected 2 h before diazepam, displayed wake-promoting effects. This PWT1-NPS stimulant effect was no longer evident in mice lacking the NPSR receptor. The PWT1 technology can be successfully applied to the NPS sequence. PWT1-NPS displayed in vitro a pharmacological profile similar to NPS. In vivo PWT1-NPS mimicked NPS effects showing higher potency and long-lasting action.

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

    Directory of Open Access Journals (Sweden)

    Simone Kühn

    2010-06-01

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

  4. Integrated quantitative pharmacology for treatment optimization in oncology

    NARCIS (Netherlands)

    van Hasselt, J.G.C.

    2014-01-01

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

  5. Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb.et Zucc.: a review.

    Science.gov (United States)

    Peng, Wei; Qin, Rongxin; Li, Xiaoli; Zhou, Hong

    2013-07-30

    Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum), also known as Reynoutria japonica Houtt and Huzhang in China, is a traditional and popular Chinese medicinal herb. Polygonum cuspidatum with a wide spectrum of pharmacological effects has been used for treatment of inflammation, favus, jaundice, scald, and hyperlipemia, etc. The present paper reviews the traditional applications as well as advances in botany, phytochemistry, pharmacodynamics, pharmacokinetics and toxicology of this plant. Finally, the tendency and perspective for future investigation of this plant are discussed, too. A systematic review of literature about Polygonum cuspidatum is carried out using resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science and others. Polygonum cuspidatum is widely distributed in the world and has been used as a traditional medicine for a long history in China. Over 67 compounds including quinones, stilbenes, flavonoids, counmarins and ligans have been isolated and identified from this plant. The root of this plant is used as the effective agent in pre-clinical and clinical practice for regulating lipids, anti-endotoxic shock, anti-infection and anti-inflammation, anti-cancer and other diseases in China and Japan. As an important traditional Chinese medicine, Polygonum cuspidatum has been used for treatment of hyperlipemia, inflammation, infection and cancer, etc. Because there is no enough systemic data about the chemical constituents and their pharmacological effects or toxicities, it is important to investigate the pharmacological effects and molecular mechanisms of this plant based on modern realization of diseases' pathophysiology. Drug target-guided and bioactivity-guided isolation and purification of the chemical constituents from this plant and subsequent evaluation of their pharmacologic effects will promote the development of new drug and make sure which

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

    Science.gov (United States)

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

    2017-10-27

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

  7. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    Directory of Open Access Journals (Sweden)

    Rianne A. de Kleine

    2013-10-01

    Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

  8. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.

    Science.gov (United States)

    de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes

    2013-10-17

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

  9. Pharmacological Evaluation of the Antidiarrhoeal Activity of ...

    African Journals Online (AJOL)

    This study presents the pharmacological evaluation of the effects of intraperitoneal injection of aqueous seed extract of Aframomum melegueta (AM) on diarrhoea, intestinal fluid secretion and gastrointestinal transit time, induced by castor oil in rodents. The results of the study revealed that AM (50-200 mg/kg) produced a ...

  10. Effect of action verbs on the performance of a complex movement.

    Directory of Open Access Journals (Sweden)

    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.

  11. Resibufogenin and cinobufagin activate central neurons through an ouabain-like action.

    Directory of Open Access Journals (Sweden)

    Ze-Jun Wang

    Full Text Available Cinobufagin and resibufogenin are two major effective bufadienolides of Chan su (toad venom, which is a Chinese medicine obtained from the skin venom gland of toads and is used as a cardiotonic and central nervous system (CNS respiratory agent, an analgesic and anesthetic, and as a remedy for ulcers. Many clinical cases showed that Chan su has severe side-effects on the CNS, causing shortness of breath, breathlessness, seizure, coma and cardiac arrhythmia. We used whole-cell recordings from brain slices to determine the effects of bufadienolides on excitability of a principal neuron in main olfactory bulb (MOB, mitral cells (MCs, and the cellular mechanism underlying the excitation. At higher concentrations, cinobufagin and resibufogenin induced irreversible over-excitation of MCs indicating a toxic effect. At lower concentrations, they concentration-dependently increased spontaneous firing rate, depolarized the membrane potential of MCs, and elicited inward currents. The excitatory effects were due to a direct action on MCs rather than an indirect phasic action. Bufadienolides and ouabain had similar effects on firing of MCs which suggested that bufadienolides activated neuron through a ouabain-like effect, most likely by inhibiting Na+/K+-ATPase. The direct action of bufadienolide on brain Na+ channels was tested by recordings from stably Nav1.2-transfected cells. Bufadienolides failed to make significant changes of the main properties of Nav1.2 channels in current amplitude, current-voltage (I-V relationships, activation and inactivation. Our results suggest that inhibition of Na+/K+-ATPase may be involved in both the pharmacological and toxic effects of bufadienolide-evoked CNS excitation.

  12. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

    Science.gov (United States)

    Russo, Ethan B; Marcu, Jahan

    2017-01-01

    The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed "pharmacological treasure trove." © 2017 Elsevier Inc. All rights reserved.

  13. Traditional uses, phytochemistry and pharmacology of the medicinal species of the genus Cordia (Boraginaceae).

    Science.gov (United States)

    Oza, Manisha J; Kulkarni, Yogesh A

    2017-07-01

    Cordia (family Boraginaceae) is a genus of deciduous flowering trees or shrubs comprising more than 300 species distributed widely in the tropical regions. The aim of this review was to provide exhaustive scientific information on traditional uses, phytochemistry and pharmacological activities of the 36 important species with medicinal value from the genus Cordia, to divulge prospects for further research on its therapeutic potential. Leaves, fruit, bark and seed of a majority of the species were found to possess abundant ethnomedicinal value, but leaves were found to be used most frequently to treat many ailments such as respiratory disorders, stomach pain, wound, inflammation, myalgia, cough, dysentery and diarrhoea. The phytochemical investigation of 36 species resulted in isolation of 293 chemical constituents from various chemical classes. The crude extracts, fractions, essential oils and pure compounds isolated from various Cordia species were reported to have a varied range of pharmacological activities. Many of the traditional uses of the genus Cordia were supported by the results obtained from pharmacological studies performed using various extracts or pure compounds. More attention should be given to the biological evaluation using pure phytochemicals and to identify the mechanism of actions and exploring this genus for new drug discovery. © 2017 Royal Pharmaceutical Society.

  14. New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

    Directory of Open Access Journals (Sweden)

    Betty Yuen Kwan Law

    2016-03-01

    Full Text Available Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM. For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri, Hu Zhang (Rhizoma polygoni cuspidati, Donglingcao (Rabdosia rubesens, Hou po (Cortex magnoliae officinalis and Chuan xiong (Rhizoma chuanxiong modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.

  15. Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen: An overview of pharmacological studies.

    Science.gov (United States)

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G

    2016-11-15

    Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015. The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library.ru, Medline/PubMed, Scopus, Web of Science, and Google Scholar. A. elata is often considered an example of a medicinal plant used in Chinese, Korean, and Japanese traditional medicine. However, the contemporary applications of Aralia in officinal medicine result primarily from a large number of pharmacological and clinical investigations carried out in the former USSR in the mid-20th century. Since the 1950s, medicinal preparations from radices of A. elata and radices of A. mandshurica have secured an established position within Russian/USSR medicine as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the Register of Medicinal Preparations of Russia. Pharmacological studies on animals have shown that Aralia increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including cold stress, immobilization, UV irradiation, and low air pressure. The phytoadaptogen exerts an effect on the central nervous, reproductive, immune, respiratory, and gastrointestinal systems; the metabolic syndrome including hypolipidemic and antidiabetic effects; and blood coagulation. Together with general properties of adaptogens, Aralia has its own specificity, which manifests in cardioprotective and antiarrhythmic activities. Studies on isolated organs, cells, and enzymes have revealed that Aralia preparations exhibit antioxidant activities and enhance sarcoplasmic reticulum Ca 2+ -ATPase

  16. Recent Advances in the Discovery and Development of Marine Natural Products with Cardiovascular Pharmacological Effects.

    Science.gov (United States)

    Zhou, Jie-Bin; Luo, Rong; Zheng, Ying-Lin; Pang, Ji-Yan

    2018-01-01

    Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-28

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

  18. The Dutch vision of clinical pharmacology

    NARCIS (Netherlands)

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

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

  19. Effective action calculation in lattice QCD

    International Nuclear Information System (INIS)

    Hoek, J.

    1983-01-01

    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.)

  20. Towards predictive cardiovascular safety : a systems pharmacology approach

    NARCIS (Netherlands)

    Snelder, Nelleke

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

  2. Pharmacological Activity and Clinical Use of PDRN

    Directory of Open Access Journals (Sweden)

    Francesco Squadrito

    2017-04-01

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

  3. Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review

    Directory of Open Access Journals (Sweden)

    Paulo Michel P. Ferreira

    2011-12-01

    Full Text Available Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X and casearvestrins (A-C, compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente

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

    Directory of Open Access Journals (Sweden)

    Kim Lawson

    2017-05-01

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

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

    Science.gov (United States)

    Lawson, Kim

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    David Stewart Koslov

    2013-08-01

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

  7. A short history of nitroglycerine and nitric oxide in pharmacology and physiology.

    Science.gov (United States)

    Marsh, N; Marsh, A

    2000-04-01

    1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with 'such precision'. Hering pursued NG ('glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of 'like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared '...a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of 'Monday disease' and of nitrate-withdrawal/overcompensation by 'Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador

  8. Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

    Directory of Open Access Journals (Sweden)

    A. L. Rozza

    2012-01-01

    Full Text Available Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH groups, K+ATP channels, α2 adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an α2-receptor antagonist, but not with a K+ATP channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H+ secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD, nitric oxide (NO, and heat shock protein-70 (HSP-70 in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, α2-adrenoceptors, NO, SOD, and HSP-70.

  9. The Cost Effectiveness of Psychological and Pharmacological Interventions for Social Anxiety Disorder: A Model-Based Economic Analysis.

    Directory of Open Access Journals (Sweden)

    Ifigeneia Mavranezouli

    Full Text Available Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder.A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion.Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT, phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs.Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately the long

  10. Type I supergravity effective action from pure spinor formalism

    International Nuclear Information System (INIS)

    Alencar, Geova

    2009-01-01

    Using the pure spinor formalism, we compute the tree-level correlation functions for three strings, one closed and two open, in N = 1 D = 10 superspace. Expanding the superfields in components, the respective terms of the effective action for the type I supergravity are obtained. All terms found agree with the effective action known in the literature. This result gives one more consistency test for the pure spinor formalism.

  11. The spillover effects of affirmative action on competitiveness and unethical behavior

    DEFF Research Database (Denmark)

    Gupta, Nabanita Datta; Banerjee, Ritwik; Villeval, Marie Claire

    2018-01-01

    We conduct an artefactual field experiment to examine various spillover effects of Affirmative Action policies in the context of castes in India. We test a) if individuals who enter tournaments in the presence of an Affirmative Action policy remain competitive after the policy has been removed...... find no spillover effect on confidence and competitiveness once Affirmative Action is withdrawn. Furthermore, the discrimination by the dominant category against the backward category is not significantly aggravated by Affirmative Action, except when individuals learn that they have lost the previous...

  12. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

    Science.gov (United States)

    Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

    2017-10-01

    Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. Natural products and biological activity of the pharmacologically active cauliflower mushroom Sparassis crispa.

    Science.gov (United States)

    Kimura, Takashi

    2013-01-01

    Sparassis crispa, also known as cauliflower mushroom, is an edible mushroom with medicinal properties. Its cultivation became popular in Japan about 10 years ago, a phenomenon that has been attributed not only to the quality of its taste, but also to its potential for therapeutic applications. Herein, I present a comprehensive summary of the pharmacological activities and mechanisms of action of its bioactive components, such as beta-glucan, and other physiologically active substances. In particular, the immunomodulatory mechanisms of the beta-glucan components are presented herein in detail.

  14. Natural Products and Biological Activity of the Pharmacologically Active Cauliflower Mushroom Sparassis crispa

    Directory of Open Access Journals (Sweden)

    Takashi Kimura

    2013-01-01

    Full Text Available Sparassis crispa, also known as cauliflower mushroom, is an edible mushroom with medicinal properties. Its cultivation became popular in Japan about 10 years ago, a phenomenon that has been attributed not only to the quality of its taste, but also to its potential for therapeutic applications. Herein, I present a comprehensive summary of the pharmacological activities and mechanisms of action of its bioactive components, such as beta-glucan, and other physiologically active substances. In particular, the immunomodulatory mechanisms of the beta-glucan components are presented herein in detail.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  16. Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations.

    Science.gov (United States)

    Parchment, Ralph E; Voth, Andrea Regier; Doroshow, James H; Berzofsky, Jay A

    2016-08-01

    Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell-tumor cell proximity). Evaluating such "trans-cellular pharmacology," in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell's biological role. We have termed this form of nearest neighbor image analysis of drug action "proximity PD microscopy," to indicate the

  17. Pharmacological effects of ethanol on ingestive behavior of the preweanling rat.

    Science.gov (United States)

    Kozlov, Andrey P; Nizhnikov, Michael E; Varlinskaya, Elena I; Spear, Norman E

    2009-12-14

    The present study was designed to test the hypothesis that sensitivity of ingestive behavior of infant rat to the pharmacological effects of ethanol changes between postnatal (P) days 9 and 12. The intake of 0.1% saccharin and water, general motor activity, and myoclonic twitching activity were assessed following administration of three doses of ethanol (0, 0.25, and 0.5 g/kg) while fluids were free available to the animals. The 0.5 g/kg dose of ethanol attenuated saccharin intake in P9 pups and enhanced saccharin intake in P12 rats. On P12 some sex-related differences emerged at 0.5 g/kg of ethanol, with saccharin intake being higher in females than in their male counterparts. Taste reactivity probe revealed that 0.5 g/kg of ethanol increased taste responsiveness to saccharin on P12 but only to infusions presented at a high rate. The results of the present study indicate that ontogenetic changes in sensitivity to the effects of ethanol on ingestive behavior occur during the second postnatal week, with P9 animals being more sensitive to the inhibitory (sedative) effects on saccharin intake and P12 rats being more sensitive to the stimulatory effects of ethanol. We suggest that acute ethanol enhanced saccharin intake via sensitization of oral response to appetitive taste stimulation.

  18. Pharmacological interactions of vasoconstrictors.

    Science.gov (United States)

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

    2009-01-01

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

  19. KIRKIA ACUMINATA OLIV.: A REVIEW OF ITS ETHNOBOTANY AND PHARMACOLOGY.

    Science.gov (United States)

    Maroyi, Alfred

    2017-01-01

    Local communities in sub-Saharan Africa have a long history of medicinal plant usage. Like in other parts of the developing world, rural and urban communities are still dependent on herbal medicines for primary health care, and the use of herbal medicines is still an integral part of their daily life and socio-cultural life style. The objective of this paper is to summarise information on the ethnobotany and pharmacology of Kirkia acuminata Oliv. throughout its distributional range. The information documented in this article is derived from books, theses, scientific journals and reports obtained from library collections, Scopus, Pubmed, MEDLINE, ISI Web of Science, Google Scholar and Science Direct. Kirkia acuminata is the most known and widely distributed Kirkia species in the genus and is one of the most popular and promising plant resources due to its several beneficial uses. Kirkia acuminata is used to treat abdominal pains, backache, cholera, constipation, cough, diarrhea, dysentery, snake bites, toothache and wounds. Other applications include its use as charcoal; hedge, ornamental or shade; stock feed, timber and source of water during drought periods. Preliminary phytochemical assessment of roots and stem bark of K. acuminata showed presence of lignans, neo-lignans, nor-carotinoids and other compounds. The extracts of K. acuminata exhibited antibacterial and antimycobacterial activities. These phytochemical compounds may be responsible for the medicinal uses and biological activities demonstrated by K. acuminata . Detailed research is required aimed at exploring mode of action of bioactive compounds of Kirkia acuminata that are responsible for the documented pharmacological effects. Kirkia acuminata is an important plant species that has potential to contribute to the primary health care and livelihood improvement of local communities in the geographical areas where it is indigenous and found in abundance.

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

    Science.gov (United States)

    Shankar, Pr; Gurung, Sb; Jha, N; Bajracharya, O; Karki, Bms; Thapa, Tp

    2011-01-01

    Small group learning sessions are used in pharmacology at the KIST Medical College, Lalitpur, Nepal. Feedback about student behaviours that enhance and hinder small group effectiveness was obtained. This will help us improve the small group sessions and will also be useful to educators using small groups in other medical schools. The small groups were self-managing with a group leader, time-keeper, recorder and presenter. Small group effectiveness was measured using the Tutorial Group Effectiveness Instrument (TGEI) developed by Singaram and co-authors. The instrument was administered in June 2010 and key findings obtained were shared with students and facilitators. The instrument was administered again in August. The mean cognitive, motivational, demotivational and overall scores were compared among different categories of respondents in June and August. Scores were also compared between June and August 2010. A total of 89 students participated in the study in June and 88 in August 2010. In June, females rated overall group productivity higher compared to males. The cognitive and motivational scores were higher in August 2010 while the demotivational score was lower. The small group effectiveness was higher in August after the educational intervention which utilised feedback about problems observed, theoretical considerations of effective small groups and how this information can be applied in practice.

  1. Pharmacological delayed preconditioning against ischaemia-induced ventricular arrhythmias: effect of an adenosine A1-receptor agonist

    OpenAIRE

    Tissier, Renaud; Souktani, Rachid; Parent de Curzon, Olivier; Lellouche, Nicolas; Henry, Patrick; Giudicelli, Jean-François; Berdeaux, Alain; Ghaleh, Bijan

    2001-01-01

    The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A1-receptor agonist (A1-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC).Eighty-nine instrumented conscious rabbits underwent a 2 consecutive days protocol. On day 1, rabbits were randomly divided into four groups: ‘Control' (saline, i.v.), ‘I-DPC' (six 4-min coronary arter...

  2. World-volume effective action of exotic five-brane in M-theory

    International Nuclear Information System (INIS)

    Kimura, Tetsuji; Sasaki, Shin; Yata, Masaya

    2016-01-01

    We study the world-volume effective action of an exotic five-brane, known as the M-theory 5"3-brane (M5"3-brane) in eleven dimensions. The supermultiplet of the world-volume theory is the N=(2,0) tensor multiplet in six dimensions. The world-volume action contains three Killing vectors k̂_I_̂"M (Î=1,2,3) associated with the U(1)"3 isometry. We find the effective T-duality rule for the eleven-dimensional backgrounds that transforms the M5-brane effective action to that of the M5"3-brane. We also show that our action provides the source term for the M5"3-brane geometry in eleven-dimensional supergravity.

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

    Science.gov (United States)

    Derendorf, H; Meltzer, E O

    2008-10-01

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

  4. 22 CFR 161.12 - Environmental effects abroad of major departmental actions.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Environmental effects abroad of major... Requirements of NEPA § 161.12 Environmental effects abroad of major departmental actions. Departmental officials shall analyze actions under their cognizance with due regard for the environmental effects in the...

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

    International Nuclear Information System (INIS)

    Podstavkova, S.; Vlcek, D.; Dubovsky, J.

    1978-01-01

    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)

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

    Science.gov (United States)

    Bailey, Kira; West, Robert

    2013-04-04

    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. Published by Elsevier B.V.

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

    Science.gov (United States)

    Madruga-Garrido, Marcos; Mir, Pablo

    2013-01-01

    Tics and other stereotyped abnormal movements can be seen as adverse effects of some pharmacologic drugs. Among these drugs, antipsychotics may provoke tardive syndromes after a chronic exposure, primarily in the case of typical antipsychotics. These syndromes include tardive tics, tardive dyskinesia, or tardive akathisia, which present with tics or stereotyped movements as a clinical phenomenon. Psychostimulants (mainly methylphenidate) have traditionally been associated with the appearance of tics due to the increased dopamine activity caused by stimulants. Nevertheless, in recent years, several studies have concluded not only that methylphenidate does not exacerbate or reactivate tics but also that tics can improve with its use in patients with associated attention deficit and hyperactivity disorder and tic disorder. Antiepileptic drugs, although infrequently, can also induce tics, with carbamazepine and lamotrigine described as tic inducers. Other antiepileptics, including levetiracetam and topiramate, have been proposed as a potential treatment for tic disorders due to a positive effect on tics, especially in those with associated epileptic disorder. Clinical and therapeutic approaches to tics and stereotyped movements after exposure to antipsychotics, stimulants, and antiepileptic drugs will be reviewed in this chapter. © 2013 Elsevier Inc. All rights reserved.

  8. Prophylactic treatment of migraine in children. Part 1. A systematic review of non-pharmacological trials

    NARCIS (Netherlands)

    Damen, L; Bruijn, J; Koes, BW; Berger, MY; Passchier, J; Verhagen, AP

    The aim of this study was to assess the efficacy of non-pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials reporting the effects of non-pharmacological prophylactic treatments

  9. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

    Science.gov (United States)

    Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

    2013-10-15

    Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Pharmacological treatment of chronic constipation: a literature review

    Directory of Open Access Journals (Sweden)

    Roshanak Salari

    2016-07-01

    Full Text Available Chronic constipation is a very common disease that is particularly commonplace among members of the elderly population. It is one of the most widespread bowel disorders, and it causes significant pain and discomfort; as such, it usually requires medical attention. The major causes of constipation are slow colonic movements and/or functional gastrointestinal disorders. This review aimed to examine the pharmacological treatments that are currently available for chronic constipation. To develop insights into the causes and treatments of chronic constipation, relevant review articles that were published on the Pubmed, Cochrane database, and Embase websites, were examined. The outputs of these studies indicated that high daily intake of fibers and fluids in addition to regular exercise can be very helpful in avoiding and treating constipation. The pharmacological treatments that are administered to treat this disease typically increase the water content of the bowel lumen, and this leads to more regular bowel movements. Novel drugs have been introduced to treat constipation, and many of these are now subject to formal research studies. Since constipation can facilitate the development of other gastrointestinal diseases, it is important that we develop an understanding the therapeutic treatments that are available with the intention of identifying which of these may represent the most effective method for treating this disease. With that objective in mind, this review was undertaken to review the clinical effectiveness of the different pharmacological treatments that are employed to treat or prevent constipation.

  12. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

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

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

    Science.gov (United States)

    Lanz, Amelia; Davis, Rebecca G

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

  14. World-volume effective action of exotic five-brane in M-theory

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Tetsuji [Research and Education Center for Natural Sciences, Keio University, Hiyoshi 4-1-1, Yokohama, Kanagawa 223-8521 (Japan); Department of Physics, Tokyo Institute of Technology,Tokyo 152-8551 (Japan); Sasaki, Shin [Department of Physics, Kitasato University,Sagamihara 252-0373 (Japan); Yata, Masaya [Department of Physics, National University of Singapore,2, Science Drive 3, Singapore 117542 (Singapore)

    2016-02-25

    We study the world-volume effective action of an exotic five-brane, known as the M-theory 5{sup 3}-brane (M5{sup 3}-brane) in eleven dimensions. The supermultiplet of the world-volume theory is the N=(2,0) tensor multiplet in six dimensions. The world-volume action contains three Killing vectors k̂{sub Î}{sup M} (Î=1,2,3) associated with the U(1){sup 3} isometry. We find the effective T-duality rule for the eleven-dimensional backgrounds that transforms the M5-brane effective action to that of the M5{sup 3}-brane. We also show that our action provides the source term for the M5{sup 3}-brane geometry in eleven-dimensional supergravity.

  15. Functional alterations of astrocytes in mental disorders: pharmacological significance as a drug target

    Directory of Open Access Journals (Sweden)

    Yutaka eKoyama

    2015-07-01

    Full Text Available Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this article, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed.

  16. The effectiveness of non-pharmacological interventions in improvement of sleep quality among non-remissive cancer patients: A systematic review of randomized trials

    Directory of Open Access Journals (Sweden)

    Fatmawati Fadli

    2016-12-01

    Full Text Available Statistical results estimated that most of non-remissive cancer patients face sleep problem and experience the symptoms of insomnia throughout and after the completion of cancer treatment. The purpose of this review was to compare the effectiveness between several types of non-pharmacological interventions and standard care or treatment to improve the sleep quality among non-remissive cancer patients. All randomized studies focused on non-pharmacological interventions to improve sleep quality among non-remissive cancer patients were included. Thirteen studies were selected with a total of 1,617 participants. The results found that only four interventions were significantly effective to improve sleep quality among non-remissive cancer patients, included cognitive behavioral therapy, relaxation and guided imagery program, self-care behavior education program, and energy and sleep enhancement program.

  17. The Spillover Effects of Affirmative Action on Competitiveness and Unethical Behavior

    DEFF Research Database (Denmark)

    Banerjee, Ritwik; Gupta, Nabanita Datta; Villeval, Marie Claire

    We conduct an artefactual field experiment to examine various spillover effects of Affirmative Action policies in the context of castes in India. We test a) if individuals who compete in the presence of Affirmative Action policies remain competitive in the same proportion after the policy has been...... frequently a tournament payment scheme. However, we find no spillover effect on confidence and competitiveness once Affirmative Action is withdrawn: any lower caste’s gain in competitiveness due to the policy is then entirely wiped out. Furthermore, the strong existing bias of the dominant caste against...... the lower caste is not significantly aggravated by Affirmative Action....

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

    Directory of Open Access Journals (Sweden)

    Takahiro eKawabe

    2013-09-01

    Full Text Available Humans can acquire the statistical features of the external world and employ them to control behaviors. Some external events occur in harmony with an agent’s action, and thus humans should also be able to acquire the statistical features between an action and its external outcome. We report that the acquired action-outcome statistical features alter the visual appearance of the action outcome. Pressing either of two assigned keys triggered visual motion whose direction was statistically biased either upward or downward, and observers judged the stimulus motion direction. Points of subjective equality (PSE for judging motion direction were shifted repulsively from the mean of the distribution associated with each key. Our Bayesian model accounted for the PSE shifts, indicating the optimal acquisition of the action-effect statistical relation. The PSE shifts were moderately attenuated when the action-outcome contingency was reduced. The Bayesian model again accounted for the attenuated PSE shifts. On the other hand, when the action-outcome contiguity was greatly reduced, the PSE shifts were greatly attenuated, and however, the Bayesian model could not accounted for the shifts. The results indicate that visual appearance can be modified by prediction based on the optimal acquisition of action-effect causal relation.

  19. Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures.

    Science.gov (United States)

    Gertsch, Jürg

    2011-07-01

    For centuries the science of pharmacognosy has dominated rational drug development until it was gradually substituted by target-based drug discovery in the last fifty years. Pharmacognosy stems from the different systems of traditional herbal medicine and its "reverse pharmacology" approach has led to the discovery of numerous pharmacologically active molecules and drug leads for humankind. But do botanical drugs also provide effective mixtures? Nature has evolved distinct strategies to modulate biological processes, either by selectively targeting biological macromolecules or by creating molecular promiscuity or polypharmacology (one molecule binds to different targets). Widely claimed to be superior over monosubstances, mixtures of bioactive compounds in botanical drugs allegedly exert synergistic therapeutic effects. Despite evolutionary clues to molecular synergism in nature, sound experimental data are still widely lacking to support this assumption. In this short review, the emerging concept of network pharmacology is highlighted, and the importance of studying ligand-target networks for botanical drugs is emphasized. Furthermore, problems associated with studying mixtures of molecules with distinctly different pharmacodynamic properties are addressed. It is concluded that a better understanding of the polypharmacology and potential network pharmacology of botanical drugs is fundamental in the ongoing rationalization of phytotherapy. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Ethnobotany, phytochemistry, and pharmacology of the genus Litsea: An update.

    Science.gov (United States)

    Wang, Yun-Song; Wen, Zheng-Qi; Li, Bi-Tao; Zhang, Hong-Bin; Yang, Jing-Hua

    2016-04-02

    modern pharmacology research. Deep and systematic phytochemical investigation of the genus Litsea and the pharmacological properties, especially its mechanism of action and toxicology, to illustrate its ethnomedicinal use, explore the therapeutic potential and support further health-care product development will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of Litsea species should be carried out in future for the safety approval of therapeutic applications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. A comparison of medical and pharmacy students' knowledge and skills of pharmacology and pharmacotherapy.

    Science.gov (United States)

    Keijsers, Carolina J P W; Brouwers, Jacobus R B J; de Wildt, Dick J; Custers, Eugene J F M; Ten Cate, Olle Th J; Hazen, Ankie C M; Jansen, Paul A F

    2014-10-01

    Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical students after their undergraduate training. Differences could serve as a starting point from which to develop joint interdisciplinary educational programmes for better prescribing. In a cross-sectional design, the knowledge and skills of advanced pharmacy and medical students were assessed, using a standardized test with three domains (basic pharmacology knowledge, clinical or applied pharmacology knowledge and pharmacotherapy skills) and eight subdomains (pharmacodynamics, pharmacokinetics, interactions and side-effects, Anatomical Therapeutic Chemical Classification groups, prescribing, prescribing for special groups, drug information, regulations and laws, prescription writing). Four hundred and fifty-one medical and 151 pharmacy students were included between August 2010 and July 2012. The response rate was 81%. Pharmacy students had better knowledge of basic pharmacology than medical students (77.0% vs. 68.2% correct answers; P students had better skills than pharmacy students in writing prescriptions (68.6% vs. 50.7%; P students had similar knowledge of applied pharmacology (73.8% vs. 72.2%, P = 0.124, δ = 0.15). Pharmacy students have better knowledge of basic pharmacology, but not of the application of pharmacology knowledge, than medical students, whereas medical students are better at writing prescriptions. Professional differences in knowledge and skills therefore might well stem from their undergraduate education. Knowledge of these differences could be harnessed to develop a joint interdisciplinary education for both students and professionals. © 2014 The British Pharmacological Society.

  2. Local Anesthetics: Review of Pharmacological Considerations

    Science.gov (United States)

    Becker, Daniel E; Reed, Kenneth L

    2012-01-01

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

  3. A pharmacologic increase in activity of plasma transaminase derived from small intestine in animals receiving an acyl CoA: diacylglycerol transferase (DGAT) 1 inhibitor.

    Science.gov (United States)

    Yokoyama, Hideaki; Kobayashi, Akio; Kondo, Kazuma; Oshida, Shin-Ichi; Takahashi, Tadakazu; Masuyama, Taku; Shoda, Toshiyuki; Sugai, Shoichiro

    2018-01-01

    Acyl CoA: diacylglycerol acyltransferase (DGAT) 1 is an enzyme that catalyzes the re-synthesis of triglycerides (TG) from free fatty acids and diacylglycerol. JTT-553 is a DGAT1 inhibitor and exhibits its pharmacological action (inhibition of re-synthesis of TG) in the enterocytes of the small intestine leading to suppression of a postprandial elevation of plasma lipids. After repeated oral dosing JTT-553 in rats and monkeys, plasma transaminase levels were increased but there were neither changes in other hepatic function parameters nor histopathological findings suggestive of hepatotoxicity. Based on the results of exploratory studies for investigation of the mechanism of the increase in transaminase levels, plasma transaminase levels were increased after dosing JTT-553 only when animals were fed after dosing and a main factor in the diet contributing to the increase in plasma transaminase levels was lipids. After dosing JTT-553, transaminase levels were increased in the small intestine but not in the liver, indicating that the origin of transaminase increased in the plasma was not the liver but the small intestine where JTT-553 exhibits its pharmacological action. The increase in small intestinal transaminase levels was due to increased enzyme protein synthesis and was suppressed by inhibiting fatty acid-transport to the enterocytes. In conclusion, the JTT-553-related increase in plasma transaminase levels is considered not to be due to release of the enzymes from injured cells into the circulation but to be phenomena resulting from enhancement of enzyme protein synthesis in the small intestine due to the pharmacological action of JTT-553 in this organ.

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

    African Journals Online (AJOL)

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

  5. Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery

    DEFF Research Database (Denmark)

    Chan, Kayi Y; Baun, Michael; de Vries, René

    2011-01-01

    We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC(1), VPAC(2) and PAC(1) receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries.......We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC(1), VPAC(2) and PAC(1) receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries....

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

    Science.gov (United States)

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

    2015-06-01

    Power is known to promote effective goal pursuit, especially when it requires one to overcome distractions or bias. We proposed that this effect involves the ability to engage and implement cognitive control. In Study 1, we demonstrated that power enhances behavioral performance on a response conflict task and that it does so by enhancing controlled processing rather than by reducing automatic processing. In Study 2, we used an event-related potential index of anterior cingulate activity to test whether power effects on control were due to enhanced conflict sensitivity or action implementation. Power did not significantly affect neural sensitivity to conflict; rather, high power was associated with a stronger link between conflict processing and intended action, relative to low power. These findings suggest a new perspective on how social factors can affect controlled processing and offer new evidence regarding the transition between conflict detection and the implementation of action control. (c) 2015 APA, all rights reserved).

  7. [Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research].

    Science.gov (United States)

    Zhao, Jun-Ning

    2017-03-01

    The moderation-integrated-balance presupposition (MIBP) of Chinese medicine compound was first proposed in this paper based on the review of function characteristics and action principles of Chinese medicine compound. Furthermore, the pharmacological problems of traditional Chinese drug research were discussed in details. The results were of important value in accelerating the transformation of traditional Chinese medicine compound, and constructing the new drug innovation and review system for traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

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

    Directory of Open Access Journals (Sweden)

    Greiner, Wolfgang

    2009-12-01

    prevention programs shows considerable heterogeneity, there is evidence for the long-term effectiveness concerning mortality, recurrent cardiac events and quality of life. Interventions based on exercise and also multicomponent interventions report more conclusive evidence for reducing mortality, while interventions focusing on psychosocial risk factors seem to be more effective in improving quality of life. Only two studies from Germany fulfill the methodological criteria and are included in this report. Additionally, 25 economic publications met the inclusion criteria. Both, quantity and quality of publications dealing with combined interventions are higher compared with those investigating single component interventions. However, there are difficulties in transferring the international results into the German health care system, because of its specific structure of the rehabilitation system. While international literature mostly shows a positive cost-effectiveness ratio of combined programs, almost without exception, studies investigate out-of hospital or home-based programs. The examination of publications evaluating the cost-effectiveness of single interventions merely shows a positive trend of exercise-based and smoking cessation programs. Due to a lack of appropriate studies, no conclusive evidence regarding psychosocial and dietary interventions is available. Altogether eleven publications concerned with ethical or social issues of non-pharmacological secondary prevention strategies are included. These studies are relatively confirm the assumption that patients with a lower socioeconomic background reflect a population at increased risk and therefore have specific needs to participate in rehabilitation programs. However, there currently remains uncertainty, whether these patients participate in rehabilitation more or less often. As barriers, which deter patients from attending, aspects like a lack of motivation, family commitments or the distance between home and

  9. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Science.gov (United States)

    Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

    2015-01-01

    Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

  10. Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies.

    Science.gov (United States)

    Macoveanu, Julian

    2014-03-27

    Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions. Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor specific investigations to complement present research mainly focused on global serotonergic manipulations. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Quednow, Boris B; Herdener, Marcus

    2016-01-01

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

  12. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

    Science.gov (United States)

    Hewitt, Matthew M; Adams, Gregory; Mazzone, Stuart B; Mori, Nanako; Yu, Li; Canning, Brendan J

    2016-06-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Wong's equations and the small x effective action in QCD

    Energy Technology Data Exchange (ETDEWEB)

    Jalilian-Marian, Jamal; Jeon, Sangyong; Venugopalan, Raju

    2000-07-13

    We propose a new form for the small x effective action in QCD. This form of the effective action is motivated by Wong's equations for classical, colored particles in non-Abelian background fields. We show that the BFKL equation, which sums leading logarithms in x, is efficiently reproduced with this form of the action. We argue that this form of the action may be particularly useful in computing next-to-leading-order results in QCD at small x.

  14. Localization of effective actions in open superstring field theory

    Science.gov (United States)

    Maccaferri, Carlo; Merlano, Alberto

    2018-03-01

    We consider the construction of the algebraic part of D-branes tree-level effective action from Berkovits open superstring field theory. Applying this construction to the quartic potential of massless fields carrying a specific worldsheet charge, we show that the full contribution to the potential localizes at the boundary of moduli space, reducing to elementary two-point functions. As examples of this general mechanism, we show how the Yang-Mills quartic potential and the instanton effective action of a Dp/D( p - 4) system are reproduced.

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

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Paul Dassonville

    2004-11-01

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

  17. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris.

    Science.gov (United States)

    Zhu, Wenyi; Du, Yijie; Meng, Hong; Dong, Yinmao; Li, Li

    2017-07-11

    Tribulus terrestris L. (TT) is an annual plant of the family Zygophyllaceae that has been used for generations to energize, vitalize, and improve sexual function and physical performance in men. The fruits and roots of TT have been used as a folk medicine for thousands of years in China, India, Sudan, and Pakistan. Numerous bioactive phytochemicals, such as saponins and flavonoids, have been isolated and identified from TT that are responsible alone or in combination for various pharmacological activities. This review provides a comprehensive overview of the traditional applications, phytochemistry, pharmacology and overuse of TT and provides evidence for better medicinal usage of TT.

  18. Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms?

    Science.gov (United States)

    Robinson, Stephen A; Dowell, Matt; Pedulla, Dominic; McCauley, Larry

    2004-01-01

    Hormonal preparations have become one of the most popular methods used for controlling fertility. The literature over the last 40 years continues to reveal how their numerous side effects negatively impact many users and even society at large. Three large cohort trials were the first to demonstrate, on a grand scale, certain emotional and behavioral associations with contraceptive use. Current contraceptive use was associated with an increase rate in depression, divorce, tranquilizer use, sexual dysfunction, and suicide and other violent and accidental deaths. Despite the advent of more "user friendly" contraceptives, the discontinuation rate secondary to side effects has changed little through the years. While in rare cases hormonal preparations can be deadly to the user, there is substantial evidence that their negative effect issues more from their emotional and behavioral properties. This paper reviews the results of over seven studies which further characterize these prominent associations, particularly with hormonal contraception, in an attempt to demonstrate their association with the intrinsic pharmacologic properties of hormonal preparations. Hormonal contraceptive users, in contrast with non users, were found to have higher rates of depression, anxiety, fatigue, neurotic symptoms, sexual disturbances, compulsion, anger, and negative menstrual effects. The question of whether the association of these maladies is directly due to the effect of taking exogenous hormones versus the psychological impact of the contraceptive behavior itself had yet to be studied. Seven small randomized-controlled trials were found in a review of the literature which studied this hypothesis in a direct way. They do not support the origination of these side effects being from the pharmacological properties of hormones. No association was found between hormone levels and emotional functioning in females. Psychiatric evaluations among IUD and oral contraceptive pill (OCP) users

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

    Directory of Open Access Journals (Sweden)

    Joan Francesc Alonso

    2015-04-01

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

  20. Mechanism of action of recombinant activated factor VII: an update.

    Science.gov (United States)

    Hedner, Ulla

    2006-01-01

    Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

  1. Clinacanthus nutans: A review of the medicinal uses, pharmacology and phytochemistry.

    Science.gov (United States)

    Alam, Ariful; Ferdosh, Sahena; Ghafoor, Kashif; Hakim, Abdul; Juraimi, Abdul Shukor; Khatib, Alfi; Sarker, Zaidul I

    2016-04-01

    Clinacanthus nutans Lindau is known as snake grass belonging to the Acanthaceae family. This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes, insects and snake bites, lesions caused by herpes simplex virus, diabetes, and gout in Malaysia, Indonesia, Thailand and China. Phytochemical investigations documented the varied contents of bioactive compounds from this plant namely flavonoids, glycosides, glycoglycerolipids, cerebrosides and monoacylmonogalatosylglycerol. The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory, antiviral, antioxidant, and anti-diabetic activities. The findings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions. However, further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability for future drugs. This review summarizes the medicinal uses, phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  2. Fluoroscopy-guided hydrostatic reduction of intussusception in infancy: role of pharmacological premedication.

    Science.gov (United States)

    Esposito, Francesco; Ambrosio, Concetta; De Fronzo, Simona; Panico, Maria Rita; D'Aprano, Marilena; Giugliano, Anna Marcella; Noviello, Domenico; Oresta, Patrizia

    2015-06-01

    Intussusception is one of the most common causes of paediatric emergency. Fluoroscopy-guided hydrostatic reduction is a common nonoperative management strategy for the treatment of intussusception. The role of pharmacological premedication in increasing the success rate of hydrostatic reduction is still controversial. The purpose of this study was to verify the presence of a possible correlation between pharmacological premedication and the percentage of hydrostatic reduction of intussusception in paediatric patients. This study considered children with a diagnosis of idiopathic intussusception treated at our hospital between January 2007 and June 2013. One group of patients underwent hydrostatic reduction by barium enema without any preliminary therapy. A second group of patients received pharmacological premedication with both a sedative and an anti-oedematous agent before the procedure. A total of 398 patients were treated with barium enema for therapeutic purposes. In the group of patients who received no premedication (n = 254), 165 (65 %) children achieved hydrostatic reduction of the intussusception. Among the patients who received pharmacological premedication prior to barium enema (n = 144), 122 (85 %) children achieved resolution of the intussusception. Our study shows that the use of pharmacological premedication is effective for the reduction of the intussusception, as its limit patient stress, fluoroscopic time and radiation dose.

  3. Indirect effects in dual radiation action

    International Nuclear Information System (INIS)

    Zaider, M.; Rossi, H.H.

    1988-01-01

    The basic aim in this paper is to establish the link between indirect effects of radiation action and the spatial distribution of radicals at the time of energy deposition as well as throughout subsequent diffusion and interaction. The fact that radicals diffuse for a finite distance before damaging a biomolecule has dramatic effects on their subsequent probability to result in lesions. Thus at very low DMSO concentrations, where p = 0.5, one expects - all other things being equal - some 75% of the lesions to result from indirect or semidirect lesions. The number calculated here is lower (15%), a direct result of the fact that such lesions involve proximity functions modulated by diffusion. At higher DMSO concentrations this percentage becomes progressively smaller, as expected. It appears thus that for low-LET radiation, the relative amount of indirect damage in single tracks (also termed intratrack or single events) action is very small. By contrast, intertrack (or two-event) contributions will have the ratio between direct and (indirect + semidirect) contributions given by p 2 /(1-p 2 ). The reason for this is that sublesions from different tracks are uniformly distributed throughout the cell nucleus; their probability of interaction should not depend on any previous diffusional processes. For the example given above (p = 0.5) they do expect 65% of intertrack (two-hit) lesions to have resulted from indirect or semidirect mechanisms. This contrast between the almost exclusively direct character of intratrack lesions and the dominant role of indirect action in intertrack lesions produced by low-LET radiation is an important conclusion of this study

  4. Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

    Directory of Open Access Journals (Sweden)

    Miyako Suzuki

    2017-01-01

    Full Text Available Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg] in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients.

  5. Multimodal compared to pharmacologic treatments for chronic tension-type headache in adolescents.

    Science.gov (United States)

    Przekop, Peter; Przekop, Allison; Haviland, Mark G

    2016-10-01

    Chronic tension-type headache (CTTH) in children and adolescents is a serious medical condition, with considerable morbidity and few effective, evidence-based treatments. We performed a chart review of 83 adolescents (age range = 13-18 years; 67 girls and 16 boys) diagnosed with CTTH. Two treatment protocols were compared: multimodal (osteopathic manipulative treatments, mindfulness, and qi gong) and pharmacologic (amitriptyline or gabapentin). Four outcomes (headache frequency, pain intensity, general health, and health interference) were assessed at three time points (baseline, 3 months, and 6 months). A fifth outcome, number of bilateral tender points, was recorded at baseline and 6 months. All five were evaluated statistically with a linear mixed model. Although both multimodal and pharmacologic treatments were effective for CTTH (time effects for all measures were significant at p treatment (the five group by time interaction effects were significant at or below the p Headache frequency in the pharmacologic group, for example, reduced from a monthly average (95% Confidence Interval shown in parentheses) of 23.9 (21.8, 26.0) to 16.4 (14.3, 18.6) and in the multimodal group from 22.3 (20.1, 24.5) to 4.9 (2.6, 7.2) (a substantial group difference). Pain intensity (worst in the last 24 hours, 0-10 scale) was reduced in the pharmacologic group from 6.2 (5.6, 6.9) to 3.4 (2.7, 4.1) and from 6.1 (5.4, 6.8) to 2.0 (1.2, 2.7) in the multimodal group (a less substantial difference). Across the other three assessments, group differences were larger for general health and number of tender points and less so for pain restriction. Multimodal treatment for adolescent CTTH appears to be effective. Randomized controlled trials are needed to confirm these promising results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Four-year follow-up study of pharmacological treatment in pathological gamblers.

    Science.gov (United States)

    Rosenberg, Oded; Dinur, Limor Klein; Dannon, Pinhas N

    2013-01-01

    In the past decade, we have witnessed the emergence of pharmacological treatments for pathological gambling with some success but many question marks. We aimed to explore pharmacological treatments that have been previously explored with some success, with the intent of comparing their efficacy and pave the way to larger placebo-controlled trials. In this study, we allocated 78 patients to 4 different types of psychotropic medications: naltrexone, topiramate, bupropion, and escitalopram. We treated patients for more than 2 years, with additional 2-year follow-ups without medication. The sample was evaluated using the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Global Assessment of Functioning, and the Visual Analog Scale to measure general well-being before enrollment as well as at 1 month, 6 months, 24 months, and 48 months after beginning medication treatment. During the first 2 years of treatment, 34 patients dropped out, with one more dropping out during the additional 2 years of follow-up. Significant improvement on all rating scales was seen in all groups after 2 years, except HAMD in the group that received topiramate. We found the naltrexone-treated group of patients to have a statistically significant lower dropout rate compared with other groups, statistically significant lower HAMD scores in comparison to the group treated with bupropion, statistically significant lower Hamilton Anxiety Rating Scale score compared to the groups treated with escitalopram and topiramate, and significantly higher Visual Analog Scale scores compared to the groups treated with bupropion and topiramate. Pathological gambling is essentially a biopsychological disorder that may be attenuated provided that patients adhere to medication. In our study, among 4 medications with different mechanisms of action, naltrexone was found to be the most effective. Placebo-controlled studies involving large numbers of subjects are required before

  7. Pharmacology national board examinations: factors that may influence performance.

    Science.gov (United States)

    Neidle, E A; Kahn, N

    1977-12-01

    Data from a survey of pharmacology courses in 60 dental schools were used to determine whether certain teaching variables affect performance in pharmacology National Board examinations. In addition, three-year class-averaged pharmacology scores and, rarely, one-year averaged scores were correlated with several admissions variables. While correlations between some admissions variables and pharmacology scores were quite good, the averaged pharmacology scores were not powerfully affected by course length, placement of the course in the curriculum, length of the curriculum, or the presence of a dentally trained pharmacologist in the department. It is suggested that other factors, related to the student and his capabilities, influence performance on National Boards. Dental pharmacology courses should be designed to given students the best possible exposure to an important basic science, not to make them perform well on National Boards, because student performance on National Boards may be independent of the nature of the didactic courses.

  8. Pharmacological chaperone reshapes the energy landscape for folding and aggregation of the prion protein

    Science.gov (United States)

    Gupta, Amar Nath; Neupane, Krishna; Rezajooei, Negar; Cortez, Leonardo M.; Sim, Valerie L.; Woodside, Michael T.

    2016-06-01

    The development of small-molecule pharmacological chaperones as therapeutics for protein misfolding diseases has proven challenging, partly because their mechanism of action remains unclear. Here we study Fe-TMPyP, a tetrapyrrole that binds to the prion protein PrP and inhibits misfolding, examining its effects on PrP folding at the single-molecule level with force spectroscopy. Single PrP molecules are unfolded with and without Fe-TMPyP present using optical tweezers. Ligand binding to the native structure increases the unfolding force significantly and alters the transition state for unfolding, making it more brittle and raising the barrier height. Fe-TMPyP also binds the unfolded state, delaying native refolding. Furthermore, Fe-TMPyP binding blocks the formation of a stable misfolded dimer by interfering with intermolecular interactions, acting in a similar manner to some molecular chaperones. The ligand thus promotes native folding by stabilizing the native state while also suppressing interactions driving aggregation.

  9. Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

    Science.gov (United States)

    Frenk, H

    1983-10-01

    The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.

  10. Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers

    NARCIS (Netherlands)

    Doorn, M. van; Vogels, J.; Tas, A.; Hoogdalem, E.J. van; Burggraaf, J.; Cohen, A.; Greef, J. van der

    2007-01-01

    Aims: To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the

  11. Transformation properties of the effective action for gauge theories

    International Nuclear Information System (INIS)

    Otten, C.M.E.

    1978-01-01

    The main purpose of this thesis is to investigate the gauge invariance properties of the effective action. In fact, the Slavnov-Taylor identities for the effective action are nothing but a compact formulation of the gauge symmetry properties of the theory. Chapter II of this thesis focuses on the derivation of the Slavnov-Taylor identities for a general gauge theory, especially the identities for proper vertices. An analysis of the group- and invariance structure of the effective action is given, using both diagrammatic and functional techniques. Moreover, the Slavnov-Taylor identities are written out explicitely up to the order g 4 , where g is the coupling constant of the theory. The general theory outlined in chapter II is applied to an SU(2) model containing vector bosons, scalar particles and leptons. Specifically, the interplay between finite one-loop effects and the invariance structure of the model is studied in a certain limit (the so-called large Higgs mass limit). It is shown that the results can be fully interpreted on the basis of the Slavnov-Taylor identities for proper vertices. This is done in chapter III. (Auth.)

  12. Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology.

    Science.gov (United States)

    Carvajal-Zarrabal, Octavio; Barradas-Dermitz, Dulce María; Orta-Flores, Zaida; Hayward-Jones, Patricia Margaret; Nolasco-Hipólito, Cirilo; Aguilar-Uscanga, M Guadalupe; Miranda-Medina, Anilú; Bujang, Kopli Bin

    2012-01-01

    Using MEDLINE and SCOPUS databases, a review of the literature from the pioneering study of 1991 until 2010 was performed on the effects on biological models of Hibiscus sabdariffa L. roselle calyx, its extracts mainly in polar solvents, or pure components found in extracts, as well as their possible relationship to these effects. Three relevant effects on lipid metabolism, antihypertensive activity, and apoptosis were observed. Our chronological review of the studies mentioned in the literature provides another opportunity to see how humans compile scientific knowledge of a chemical structure-physiological activity relationship starting from an ethnobotanical-ethnopharmagognosy contribution. The chemical components that are the main active principles in the physiological activities of Hibiscus sabdariffa L. calyx are anthocyanins and polyphenols (protocatechuic acid and quercetin). Advances have also been made in the elucidation of action mechanisms. Additionally, it has become clear that the lack of standardization in terms of chemical components of the material arising from Hibiscus sabdariffa L. used in testing on biological models imposes limits on the possibility of carrying out comparative analyses between studies. Fortunately, more recent studies are overcoming this obstacle by reporting component concentrations of assumed active principles; however, complete analysis of the extract, if this is to be considered as a therapeutic agent, is not commonly reported in the aforesaid studies. If one of the eventual scenarios for Hibiscus sabdariffa L. calyx is as a therapeutic agent in communities with economic limitations, then studies of a pharmacological nature should guarantee the effectiveness, safety, and tolerability of this material, which is widely accepted to be associated with chemical complexity, thus making this knowledge necessary.

  13. Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology

    Science.gov (United States)

    Carvajal-Zarrabal, Octavio; Barradas-Dermitz, Dulce María; Orta-Flores, Zaida; Hayward-Jones, Patricia Margaret; Nolasco-Hipólito, Cirilo; Aguilar-Uscanga, M Guadalupe; Miranda-Medina, Anilú; Bujang, Kopli Bin

    2012-01-01

    Using MEDLINE and SCOPUS databases, a review of the literature from the pioneering study of 1991 until 2010 was performed on the effects on biological models of Hibiscus sabdariffa L. roselle calyx, its extracts mainly in polar solvents, or pure components found in extracts, as well as their possible relationship to these effects. Three relevant effects on lipid metabolism, antihypertensive activity, and apoptosis were observed. Our chronological review of the studies mentioned in the literature provides another opportunity to see how humans compile scientific knowledge of a chemical structure–physiological activity relationship starting from an ethnobotanical–ethnopharmagognosy contribution. The chemical components that are the main active principles in the physiological activities of Hibiscus sabdariffa L. calyx are anthocyanins and polyphenols (protocatechuic acid and quercetin). Advances have also been made in the elucidation of action mechanisms. Additionally, it has become clear that the lack of standardization in terms of chemical components of the material arising from Hibiscus sabdariffa L. used in testing on biological models imposes limits on the possibility of carrying out comparative analyses between studies. Fortunately, more recent studies are overcoming this obstacle by reporting component concentrations of assumed active principles; however, complete analysis of the extract, if this is to be considered as a therapeutic agent, is not commonly reported in the aforesaid studies. If one of the eventual scenarios for Hibiscus sabdariffa L. calyx is as a therapeutic agent in communities with economic limitations, then studies of a pharmacological nature should guarantee the effectiveness, safety, and tolerability of this material, which is widely accepted to be associated with chemical complexity, thus making this knowledge necessary. PMID:27186114

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

    Directory of Open Access Journals (Sweden)

    Karoline Koch

    2014-01-01

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

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

    Science.gov (United States)

    Koch, Karoline; Havermann, Susannah; Büchter, Christian

    2014-01-01

    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. PMID:24895670

  16. Pharmacological screening technologies for venom peptide discovery.

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

    Hamburger, Matthias

    2007-01-01

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

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

    Science.gov (United States)

    Kalinec, Federico

    2005-01-01

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

  19. Patients and ICU nurses' perspectives of non-pharmacological interventions for pain management.

    Science.gov (United States)

    Gélinas, Céline; Arbour, Caroline; Michaud, Cécile; Robar, Lauren; Côté, José

    2013-11-01

    Pain is a major stressor for critically ill patients. To maximize pain relief, non-pharmacological interventions are an interesting avenue to explore. The study aim was to describe the perspectives of patients/family members and nurses about the usefulness, relevance and feasibility of non-pharmacological interventions for pain management in the intensive care unit (ICU). A qualitative descriptive design was used. Patients/family members (n = 6) with a previous experience of ICU hospitalization and ICU nurses (n = 32) were recruited. Using a semi-structured discussion guide, participants were asked to share their perspective about non-pharmacological interventions that they found useful, relevant and feasible for pain management in the ICU. Interventions were clustered into five categories: a) cognitive-behavioural, b) physical, c) emotional support, d) helping with activities of daily living and, e) creating a comfortable environment. A total of eight focus groups (FGs) with patients/family members (two FGs) and ICU nurses (six FGs) were conducted. Overall, 33 non-pharmacological interventions were discussed. The top four non-pharmacological interventions found to be useful, relevant and feasible in at least half of the FGs were music therapy and distraction (cognitive-behavioural category), simple massage (physical category) and family presence facilitation (emotional support category). Interestingly, patients/family members and nurses showed different interests towards some interventions. For instance, patients discussed more about active listening/reality orientation, while nurses talked mostly about teaching/positioning. Four non-pharmacological interventions reached consensus in patients and nurses' FGs to be useful, relevant and feasible for pain management in the ICU. Other interventions seemed to be influenced by personal experience or professional role of the participants. While more evidence is required to conclude to their effectiveness, ICU nurses can

  20. Pharmacological Profile of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2015-01-01

    Full Text Available The female inflorescences of hops (Humulus lupulus L., a well-known bittering agent used in the brewing industry, have long been used in traditional medicines. Xanthohumol (XN is one of the bioactive substances contributing to its medical applications. Among foodstuffs XN is found primarily in beer and its natural occurrence is surveyed. In recent years, XN has received much attention for its biological effects. The present review describes the pharmacological aspects of XN and summarizes the most interesting findings obtained in the preclinical research related to this compound, including the pharmacological activity, the pharmacokinetics, and the safety of XN. Furthermore, the potential use of XN as a food additive considering its many positive biological effects is discussed.

  1. A gauge/gravity relation in the one-loop effective action

    International Nuclear Information System (INIS)

    Basar, Goekce; Dunne, Gerald V

    2010-01-01

    We identify an unusual new gauge/gravity relation: the one-loop effective action for a massive spinor in 2n-dimensional AdS space is expressed in terms of precisely the same function (a certain multiple gamma function) as the one-loop effective action for a massive charged scalar in 4n dimensions in a maximally symmetric background electromagnetic field (one for which the eigenvalues of F μν are maximally degenerate, corresponding in four dimensions to a self-dual field, equivalently to a field of definite helicity), subject to the identification F 2 ↔Λ, where Λ is the gravitational curvature. Since these effective actions generate the low energy limit of all one-loop multi-leg graviton or gauge amplitudes, this implies a nontrivial gauge/gravity relation at the non-perturbative level and at the amplitude level. (fast track communication)

  2. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

    Science.gov (United States)

    Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

    2015-01-01

    Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

  3. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond

    2017-01-01

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

  4. Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

    Directory of Open Access Journals (Sweden)

    Elga Esposito

    2015-01-01

    Full Text Available Beyond reperfusion therapies, there are still no widely effective therapies for ischemic stroke. Although much progress has been made to define the molecular pathways involved, targeted neuroprotective strategies have often failed in clinical trials. An emerging hypothesis suggests that focusing on single targets and mechanisms may not work since ischemic stroke triggers multiple pathways in multiple cell types. In this review, we briefly survey and assess the opportunities that may be afforded by pre- and postconditioning therapies, with particular attention to pharmacologic pre- and postconditioning. Pharmacologic conditioning may be defined as the use of chemical agents either before or shortly after stroke onset to trigger mechanisms of endogenous tolerance that are thought to involve evolutionarily conserved signals that offer broad protection against ischemia. Importantly, many of the pharmacologic agents may also have been previously used in humans, thus providing hope for translating basic mechanisms into clinical applications.

  5. Pharmacological Fingerprints of Contextual Uncertainty.

    Directory of Open Access Journals (Sweden)

    Louise Marshall

    2016-11-01

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

  6. Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system

    Directory of Open Access Journals (Sweden)

    Zhong ZF

    2018-05-01

    Full Text Available Zhifeng Zhong,1 Jing Han,1 Jizhou Zhang,1 Qing Xiao,1 Juan Hu,1,2 Lidian Chen1,2 1Institute of Materia Medica, Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2School of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China Abstract: The primary objective of this review article was to summarize comprehensive information related to the neuropharmacological activity, mechanisms of action, toxicity, and safety of salidroside in medicine. A number of studies have revealed that salidroside exhibits neuroprotective activities, including anti-Alzheimer’s disease, anti-Parkinson’s disease, anti-Huntington’s disease, anti-stroke, anti-depressive effects, and anti-traumatic brain injury; it is also useful for improving cognitive function, treating addiction, and preventing epilepsy. The mechanisms underlying the potential protective effects of salidroside involvement are the regulation of oxidative stress response, inflammation, apoptosis, hypothalamus-pituitary-adrenal axis, neurotransmission, neural regeneration, and the cholinergic system. Being free of side effects makes salidroside potentially attractive as a candidate drug for the treatment of neurological disorders. It is evident from the available published literature that salidroside has potential use as a beneficial therapeutic medicine with high efficacy and low toxicity to the central nervous system. However, the definite target protein molecules remain unclear, and clinical trials regarding this are currently insufficient; thus, guidance for further research on the molecular mechanisms and clinical applications of salidroside is urgent. Keywords: salidroside, Alzheimer’s disease, Parkinson’s disease, stroke, cognitive impairment, clinical trials

  7. A yeast expression system for functional and pharmacological studies of the malaria parasite Ca2+/H+ antiporter

    Directory of Open Access Journals (Sweden)

    Salcedo-Sora J

    2012-08-01

    Full Text Available Abstract Background Calcium (Ca2+ signalling is fundamental for host cell invasion, motility, in vivo synchronicity and sexual differentiation of the malaria parasite. Consequently, cytoplasmic free Ca2+ is tightly regulated through the co-ordinated action of primary and secondary Ca2+ transporters. Identifying selective inhibitors of Ca2+ transporters is key towards understanding their physiological role as well as having therapeutic potential, therefore screening systems to facilitate the search for potential inhibitors are a priority. Here, the methodology for the expression of a Calcium membrane transporter that can be scaled to high throughputs in yeast is presented. Methods The Plasmodium falciparum Ca2+/H+ antiporter (PfCHA was expressed in the yeast Saccharomyces cerevisiae and its activity monitored by the bioluminescence from apoaequorin triggered by divalent cations, such as calcium, magnesium and manganese. Results Bioluminescence assays demonstrated that PfCHA effectively suppressed induced cytoplasmic peaks of Ca2+, Mg2+ and Mn2+ in yeast mutants lacking the homologue yeast antiporter Vcx1p. In the scalable format of 96-well culture plates pharmacological assays with a cation antiporter inhibitor allowed the measurement of inhibition of the Ca2+ transport activity of PfCHA conveniently translated to the familiar concept of fractional inhibitory concentrations. Furthermore, the cytolocalization of this antiporter in the yeast cells showed that whilst PfCHA seems to locate to the mitochondrion of P. falciparum, in yeast PfCHA is sorted to the vacuole. This facilitates the real-time Ca2+-loading assays for further functional and pharmacological studies. Discussion The functional expression of PfCHA in S. cerevisiae and luminescence-based detection of cytoplasmic cations as presented here offer a tractable system that facilitates functional and pharmacological studies in a high-throughput format. PfCHA is shown to behave as a divalent

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

    Science.gov (United States)

    Niederberger, E; Kuner, R; Geißlinger, G

    2015-10-01

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

  9. Selective effects of an octopus toxin on action potentials

    Science.gov (United States)

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  10. Pharmacological characterisation of murine α4β1δ GABAA receptors expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Villumsen, Inge S; Wellendorph, Petrine; Smart, Trevor G

    2015-01-01

    BACKGROUND: GABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence on extrasyn......BACKGROUND: GABAA receptor subunit composition has a profound effect on the receptor's physiological and pharmacological properties. The receptor β subunit is widely recognised for its importance in receptor assembly, trafficking and post-translational modifications, but its influence...

  11. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  12. Duality symmetries and the Type II string effective action

    International Nuclear Information System (INIS)

    Bergshoeff, E.

    1996-01-01

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

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

    Science.gov (United States)

    Pacifici, Gian M

    2016-01-01

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

  14. Effect of mutagen combined action on Chlamydomonas reinhardtii cells. II. Dependence of lethal effect on mutagen dose and on conditions of cultivation following mutagen action. [In Slovak

    Energy Technology Data Exchange (ETDEWEB)

    Podstavkova, S; Vlcek, D; Dubovsky, J [Komenskeho Univ., Bratislava (Czechoslovakia). Prirodovedecka Fakulta

    1978-01-01

    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.

  15. A review of traditional uses, phytochemistry and pharmacology of Portulaca oleracea L.

    Science.gov (United States)

    Iranshahy, Milad; Javadi, Behjat; Iranshahi, Mehrdad; Jahanbakhsh, Seyedeh Pardis; Mahyari, Saman; Hassani, Faezeh Vahdati; Karimi, Gholamreza

    2017-06-09

    Portulaca oleracea L. is a widespread medicinal plant that is used not only as an edible plant, but also as a traditional medicine for alleviating a wide spectrum of diseases. It is a well-known plant in the European Traditional Medicine. PA is mentioned by Dioscorides (40-90 CE), with the name of "andrachne". In this study, we provide detailed information on botany, traditional uses, phytochemistry, pharmacological uses, pharmacokinetics and safety of P. oleracea. An extensive search on electronic databases including PubMed, Web of Science, Google Scholar, ScienceDirect, Scopus, conference papers, local herbal encyclopedias, articles, books (in English, French, Arabic, Persian, etc.) and also a number of unpublished handwritten manuscripts was done to find articles have been published between 1956 and 2015 on pharmacology and phytochemistry of P. oleracea. P. oleracea has been addressed in De Materia Medica as an astringent, and a remedy for headaches, inflammation of the eyes and other organs, burning of the stomach, erysipela, disorders of the bladder, numbness of the teeth, excessive sexual desire, burning fevers, worms, dysentery, hemorrhoids, eruptions of blood, and bites. Phytochemical investigations revealed that this plant a wide range of secondary metabolites including alkaloids, terpenoids, flavonoids and organic acids. The most important pharmacological activities are renoprotective activities and effects on metabolism. P. oleracea could successfully decrease blood glucose and lipid profile of patients with metabolic syndrome. The safety of P. oleracea has been reported in many clinical trials. Modern pharmacological studies have now proven many traditional uses of P. oleracea, including anti-hyperglycemic and anti-hyperlipidemic, renoprotective and hepatoprotective effects. In addition, in many clinical trials P. oleracea showed no adverse effects and constipation was reported as the most frequent adverse effect. Copyright © 2017 Elsevier Ireland Ltd

  16. Problems of pharmacological supply of disaster medicine

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  17. [Pharmacological study on hemostasis, analgesic and anti inflammation effects of the alcohol extract of Hibiscus tiliaceus].

    Science.gov (United States)

    Qiu, Fen; Tian, Hui; Zhang, Zhi; Yuan, Xian-Ling; Tan, Yuan-Feng; Ning, Xiao-Qing

    2013-10-01

    To study the effects of hemostasis, analgesic and anti inflammation of the alcohol extract of Hibiscus tiliaceus and offer pharmacological and experimental basis for its safe and effective use in clinic. The effects of hemostasist were observed with tail breaking method, capillary tube method and slide method; Hot board and body distortion induced by acetic acid methods were applied in mice analgesia experiment, the mice model of acute auricle swelling induced by dmi ethylbenzene and capillary permeability induced by acetic acid were applied to observe the anti inflammatory effects. The alcohol extract of Hibiscus tiliaceus could significantly reduce the bleeding time and the clotting time, delay the plant reaction time and reduce the writhing times of the mice, and it also had effect on inhibiting swelling of mice ear and the permeability of the capillary. These results suggest that the alcohol extract of Hibiscus tiliaceus has the effects of hemostasis, analgesic and anti inflammation.

  18. A "novel" association to treat pain: tramadol/dexketoprofen. The first drug of a "new pharmacological class".

    Science.gov (United States)

    Fornasari, D; Allegri, M; Gerboni, S; Fanelli, Guido

    2017-04-28

     Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic "ladder" for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and

  19. Action video game training reduces the Simon Effect.

    Science.gov (United States)

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

    2016-04-01

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

  20. Pharmacological treatment for memory disorder in multiple sclerosis.

    Science.gov (United States)

    He, Dian; Zhang, Yun; Dong, Shuai; Wang, Dongfeng; Gao, Xiangdong; Zhou, Hongyu

    2013-12-17

    authors. We contacted principal investigators of included studies for additional data or confirmation. We included seven randomised controlled trials (RCTs) involving 625 people mostly with relapsing-remitting, secondary-progressive and primary-progressive MS, evaluating the absolute efficacy of donepezil, ginkgo biloba, memantine and rivastigmine versus placebo in improving memory performance with diverse assessment scales. Overall, clinical and methodological heterogeneities existed across these studies. Moreover, most of them had methodological limitations on non-specific selections of targeted sample, non-matched variables at baseline or incomplete outcome data (high attrition bias). Only the two studies on donepezil had clinical and methodological homogeneity and relatively low risks for bias. One RCT evaluating estriol versus placebo is currently ongoing.We could not carry out a meta-analysis due to the heterogeneities across studies and the high attrition bias. A subgroup analysis for donepezil versus placebo showed no treatment effects on total recall on the Selective Reminding Test (mean difference (MD) 1.68; 95% confidence interval (CI) -2.21 to 5.58), total correct scores on the 10/36 Spatial Recall Test (MD -0.93; 95% CI -3.18 to 1.32), the Symbol Digit Modalities Test (MD -1.27; 95% CI -3.15 to 0.61) and the Paced Auditory Serial Addition Test (2+3 sec) (MD 2.23; 95% CI -1.87 to 6.33). Concerning safety, the main adverse events were: diarrhoea (risk ratio (RR) 3.88; 95% CI 1.66 to 9.05), nausea (RR 1.71; 95% CI 0.93 to 3.18) and abnormal dreams (RR 2.91; 95% CI 1.38 to 6.14). However, the results in both studies were subjected to a serious imprecision resulting from the small sample sizes and the low power of test (lower than 80%), which contributed to a moderate quality of the evidence. No serious adverse events were attributed to the treatments in all experimental groups. We found no convincing evidence to support the efficacy of pharmacological symptomatic

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

    Directory of Open Access Journals (Sweden)

    Abderrazak Hajjioui

    2014-01-01

    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.

  2. Effects of non-pharmacological interventions on inflammatory biomarker expression in patients with fibromyalgia: a systematic review.

    Science.gov (United States)

    Sanada, Kenji; Díez, Marta Alda; Valero, Montserrat Salas; Pérez-Yus, María Cruz; Demarzo, Marcelo M P; García-Toro, Mauro; García-Campayo, Javier

    2015-09-26

    Fibromyalgia (FM) is a prevalent disorder. However, few studies have evaluated the effect of treatment interventions on biomarker expression. The aim of this review was to explore the efficacy of non-pharmacological interventions on inflammatory biomarker expression, specifically cytokines, neuropeptides and C-reactive protein (CRP), in FM patients. A literature search using PubMed, EMBASE, PsycINFO and the Cochrane library was performed from January 1990 to March 2015. Randomized controlled trials (RCTs) and non-RCTs published in English, French or Spanish were eligible. Twelve articles with a total of 536 participants were included. After exercise, multidisciplinary, or dietary interventions in FM patients, interleukin (IL) expression appeared reduced, specifically serum IL-8 and IL-6 (spontaneous, lipopolysaccharide (LPS)-induced, or serum). Furthermore, the changes to insulin-like growth factor 1 (IGF-1) levels might indicate a beneficial role for fatigue in obese FM patients. In contrast, evidence of changes in neuropeptide and CRP levels seemed inconsistent. Despite minimal evidence, our findings indicate that exercise interventions might act as an anti-inflammatory treatment in FM patients and ameliorate inflammatory status, especially for pro-inflammatory cytokines. Additional RCTs focused on the changes to inflammatory biomarker expression after non-pharmacological interventions in FM patients are needed.

  3. Explicit learning of arbitrary and non-arbitrary action-effect relations in adults and 4-year-olds

    Directory of Open Access Journals (Sweden)

    Stephan Alexander eVerschoor

    2012-02-01

    Full Text Available Ideomotor theories claim that carrying out a movement that produces a perceivable effect creates a bidirectional association between the two, which can be used by action control processes to retrieve the associated action by anticipating its outcome. Indeed, previous implicit-learning studies have shown that practice renders novel but action-contingent stimuli effective retrieval cues of the action they used to follow, suggesting that experiencing sequences of actions and effects creates bidirectional action-effect associations. We investigated whether action-effect associations are also acquired under explicit-learning conditions and whether familiar action-effect relations (such as between a trumpet and a trumpet sound are learned the same way as novel, arbitrary relations are. We also investigated whether these factors affect adults and 4-year-old children equally. Our findings suggest that explicit learning produces the same bidirectional action-effect associations as implicit learning does, that non-arbitrary relations improve performance without affecting learning per se, and that adults and young children show equivalent performance—apart from the common observation that children have greater difficulty to withstand stimulus-induced action tendencies.

  4. Exact CTP renormalization group equation for the coarse-grained effective action

    International Nuclear Information System (INIS)

    Dalvit, D.A.; Mazzitelli, F.D.

    1996-01-01

    We consider a scalar field theory in Minkowski spacetime and define a coarse-grained closed time path (CTP) effective action by integrating quantum fluctuations of wavelengths shorter than a critical value. We derive an exact CTP renormalization group equation for the dependence of the effective action on the coarse-graining scale. We solve this equation using a derivative expansion approach. Explicit calculation is performed for the λφ 4 theory. We discuss the relevance of the CTP average action in the study of nonequilibrium aspects of phase transitions in quantum field theory. copyright 1996 The American Physical Society

  5. Overview of non-pharmacological intervention for dementia and principles of brain-activating rehabilitation.

    Science.gov (United States)

    Yamaguchi, Haruyasu; Maki, Yohko; Yamagami, Tetsuya

    2010-12-01

    Non-pharmacological interventions for dementia are likely to have an important role in delaying disease progression and functional decline. Research into non-pharmacological interventions has focused on the differentiation of each approach and a comparison of their effects. However, Cochrane Reviews on non-pharmacological interventions have noted the paucity of evidence regarding the effects of these interventions. The essence of non-pharmacological intervention is dependent of the patients, families, and therapists involved, with each situation inevitably being different. To obtain good results with non-pharmacological therapy, the core is not 'what' approach is taken but 'how' the therapists communicate with their patients. Here, we propose a new type of rehabilitation for dementia, namely brain-activating rehabilitation, that consists of five principles: (i) enjoyable and comfortable activities in an accepting atmosphere; (ii) activities associated with empathetic two-way communication between the therapist and patient, as well as between patients; (iii) therapists should praise patients to enhance motivation; (iv) therapists should try to offer each patient some social role that takes advantage of his/her remaining abilities; and (v) the activities should be based on errorless learning to ensure a pleasant atmosphere and to maintain a patient's dignity. The behavioral and cognitive status is not necessarily a reflection of pathological lesions in the brain; there is cognitive reserve for improvement. The aim of brain-activating rehabilitation is to enhance patients' motivation and maximize the use of their remaining function, recruiting a compensatory network, and preventing the disuse of brain function. The primary expected effect is that patients recover a desire for life, as well as their self-respect. Enhanced motivation can lead to improvements in cognitive function. Amelioration of the behavioral and psychological symptoms of dementia and improvements in

  6. Cleome viscosa (wild mustard): a review on ethnobotany, phytochemistry, and pharmacology.

    Science.gov (United States)

    Mali, Ravindra G

    2010-01-01

    Cleome viscosa Linn. (Capparidaceae), commonly known as "wild or dog mustard," is an annual, sticky herb found as a common weed all over the plains of India and throughout the tropics of the world. The whole plant and its parts (leaves, seeds, and roots) are widely used in traditional and folkloric systems of medicine. In traditional systems of medicine the plant is reported to possess beneficial effects as an anthelmintic, antiseptic, carminative, antiscorbutic, sudorific, febrifuge, and cardiac stimulant. Following the various traditional claims for the use of C. viscosa (CV) as a cure of numerous diseases, considerable efforts have been made by researchers to verify its utility through scientific pharmacological screenings. The pharmacological studies have shown that CV possesses various notable biological activities such as anthelmintic, antimicrobial, analgesic, antiinflammatory, immunomodulatory, antipyretic, psychopharmacological, antidiarrheal, and hepatoprotective activities. A wide variety of phytoprinciples have been isolated from the plant. The present review is an effort to consolidate traditional, ethnobotanical, phytochemical, and pharmacological information available on C. viscosa.

  7. Zeta Functions, Renormalization Group Equations, and the Effective Action

    International Nuclear Information System (INIS)

    Hochberg, D.; Perez-Mercader, J.; Molina-Paris, C.; Visser, M.

    1998-01-01

    We demonstrate how to extract all the one-loop renormalization group equations for arbitrary quantum field theories from knowledge of an appropriate Seeley-DeWitt coefficient. By formally solving the renormalization group equations to one loop, we renormalization group improve the classical action and use this to derive the leading logarithms in the one-loop effective action for arbitrary quantum field theories. copyright 1998 The American Physical Society

  8. Pharmacological and non-pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults.

    Science.gov (United States)

    Prabhakar, Hemanshu; Singh, Gyaninder Pal; Ali, Zulfiqar; Kalaivani, Mani; Smith, Martha A

    2016-02-12

    . We used a fixed-effect model where there was no evidence of significant heterogeneity between studies and a random-effects model if heterogeneity was likely. We included 66 studies with 7840 participants in the review, though most analyses were based on data from fewer participants. In total there are 17 studies awaiting classification. No studies were at a low risk of bias. We noted substantial statistical and clinical heterogeneity between trials. Most of the studies reported the primary outcome pain as assessed by verbal response from participants in an awake state but some trials reported withdrawal of the injected limb as a proxy for pain after induction of anaesthesia in response to rocuronium administration. Few studies reported adverse events and no study reported heart rate and blood pressure changes after administration of rocuronium. Lidocaine was the most commonly studied intervention drug, used in 29 trials with 2256 participants. The risk ratio (RR) of pain on injection if given lidocaine compared to placebo was 0.23 (95% confidence interval (CI) 0.17 to 0.31; I² = 65%, low quality of evidence). The RR of pain on injection if fentanyl and remifentanil were given compared to placebo was 0.42 (95% CI 0.26 to 0.70; I² = 79%, low quality of evidence) and (RR 0.10, 95% CI 0.04 to 0.26; I² = 74%, low quality of evidence), respectively. Pain on injection of intervention drugs was reported with the use of lidocaine and acetaminophen in one study. Cough was reported with the use of fentanyl (one study), remifentanil (five studies, low quality evidence) and alfentanil (one study). Breath holding and chest tightness were reported with the use of remifentanil in two studies (very low quality evidence) and one study (very low quality evidence), respectively. The overall rate of complications was low. The evidence to suggest that the most commonly investigated pharmacological interventions reduce pain on injection of rocuronium is of low quality due to risk of

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

    Science.gov (United States)

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

    2015-04-01

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

  10. Pharmacological characterization of the diuretic effect of Hibiscus sabdariffa Linn (Malvaceae) extract.

    Science.gov (United States)

    Alarcón-Alonso, Javier; Zamilpa, Alejandro; Aguilar, Francisco Alarcón; Herrera-Ruiz, Maribel; Tortoriello, Jaime; Jimenez-Ferrer, Enrique

    2012-02-15

    Hibiscus sabdariffa L. (Malvaceae) populary known in Mexico as "Jamaica", "flor de Jamaica", has widely used in Mexican Traditional Medicine as antihypertensive and diuretic, although the latter activity has been reported the present work show evidence about the diuretic, natriuretic and potassium-sparing effects. To evaluate the diuretic activity of Hibiscus sabdariffa aqueous extract on in vivo and in situ models. The Hibiscus sabdariffa aqueous extract was administrated in increasing doses and evaluated the diuresis produced and disposal of electrolytes. Moreover, in isolated kidney was determined the renal filtration rate with plant extract, furosemide and amiloride. The yield of Hibiscus sabdariffa aqueous extraction was 28.3% and the chemical standardization from 1 g of extract was: 56.5 mg delphinidin-3-O-sambubioside, 20.8 mg/g cyanidin-3-O-sambubioside, 3.2 mg/g quercetin, 2.1 mg/g rutin and 2.7 mg/g chlorogenic acid. The diuretic and natriuretic effect of Hibiscus sabdariffa aqueous extract showed a dose-dependent behavior. The pharmacological constants of natriuretic effect was ED50=86 mg/kg and Emax=0.9 mEq/100 g/5 h. In the model of kidney in situ was observed that renal filtration increased 48% with the aqueous extract of Hibiscus sabdariffa and an additive effect when was perfuse with furosemide. The compound presents in Hibiscus sabdariffa as quercetin had effect on the vascular endothelium causing oxide nitric release, increasing renal vasorelaxation by increasing kidney filtration. Therefore, the diuretic effect of Hibiscus sabdariffa may be mediated by nitric oxide release. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. An addendum to the Heisenberg-Euler effective action beyond one loop

    Energy Technology Data Exchange (ETDEWEB)

    Gies, Holger; Karbstein, Felix [Helmholtz-Institut Jena,Fröbelstieg 3, 07743 Jena (Germany); Theoretisch-Physikalisches Institut, Abbe Center of Photonics,Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, 07743 Jena (Germany)

    2017-03-21

    We study the effective interactions of external electromagnetic fields induced by fluctuations of virtual particles in the vacuum of quantum electrodynamics. Our main focus is on these interactions at two-loop order. We discuss in detail the emergence of the renowned Heisenberg-Euler effective action from the underlying microscopic theory of quantum electrodynamics, emphasizing its distinction from a standard one-particle irreducible effective action. In our explicit calculations we limit ourselves to constant and slowly varying external fields, allowing us to adopt a locally constant field approximation. One of our main findings is that at two-loop order there is a finite one-particle reducible contribution to the Heisenberg-Euler effective action in constant fields, which was previously assumed to vanish. In addition to their conceptual significance, our results are relevant for high-precision probes of quantum vacuum nonlinearity in strong electromagnetic fields.

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Computing the effective action with the functional renormalization group

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

  14. Local analgesia in paediatric dentistry: a systematic review of techniques and pharmacologic agents.

    Science.gov (United States)

    Klingberg, G; Ridell, K; Brogårdh-Roth, S; Vall, M; Berlin, H

    2017-10-01

    To evaluate the evidence supporting effects and adverse effects of local analgesia using different pharmacological agents and injection techniques during dental treatment in children and adolescents aged 3-19 years. A systematic literature search of databases including PubMed, Cochrane, and Scopus was conducted in November 2016. The PRISMA-statement was followed. Two review authors independently assessed the selected randomised control trials for risk of bias and quality. 725 scientific papers were identified. 89 papers were identified to be read in full text of which 80 were excluded. Finally, 9 papers were evaluated for quality and risk of bias. Many of the included papers had methodological shortcomings affecting the possibility to draw conclusions. Information about ethical clearance and consent were missing in some of the included papers. No alarming adverse effects were identified. One study was assessed as having low risk of bias. This reported inferior alveolar nerve block to be more effective than buccal infiltration for dental treatment of mandibular molars, while no differences were found regarding pharmacological agents. At present, there is insufficient evidence in support of any pharmacologic agent or injection technique as being superior compared to others. There is a need for more rigorous studies which also handle the ethical issues of including children in potentially painful studies.

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

    Science.gov (United States)

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

    2016-09-15

    phytoconstituents. The present review indicated that A. cordifolia is a valuable medicinal plant with multiple pharmacological effects. However, further research on the pharmacological mechanism of action of this plant is recommended in order to unravel the pharmacokinetics, pharmacodynamics, clinical relevance and toxicity of its extracts as well as constituents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Human Pharmacology of Mephedrone in Comparison with MDMA.

    Science.gov (United States)

    Papaseit, Esther; Pérez-Mañá, Clara; Mateus, Julián-Andrés; Pujadas, Mitona; Fonseca, Francina; Torrens, Marta; Olesti, Eulàlia; de la Torre, Rafael; Farré, Magí

    2016-10-01

    Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.

  17. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2008-01-01

    Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  18. Combined chemical (fluoranthene) and drought effects on Lumbricus rubellus demonstrate the applicability of the independent action model for multiple stressor assessment.

    Science.gov (United States)

    Long, Sara M; Reichenberg, Fredrik; Lister, Lindsay J; Hankard, Peter K; Townsend, Joanna; Mayer, Philipp; Wright, Julian; Holmstrup, Martin; Svendsen, Claus; Spurgeon, David J

    2009-03-01

    The combined effect of a chemical (fluoranthene) and a nonchemical stress (reduced soil moisture content) to the widely distributed earthworm Lumbricus rubellus were investigated in a laboratory study. Neither fluoranthene (up to 500 microg/g) nor low soil moisture (15% below optimal) had a significant effect on the survival of the exposed worms, but a significant effect on reproduction (cocoon production rate) was found for both stressors (p IA) model that is widely used in pharmacology and chemical mixture risk assessment. Fitting of the IA model provided a good description of the combined stressor data (accounting for 53.7% of total variation) and was the most parsimonious model describing joint effect (i.e., the description of the data was not improved by addition of further parameters accounting for synergism or antagonism). Thus, the independent action of the two responses was further supported by measurement of internal fluoranthene exposure. The chemical activity of fluoranthene in worm tissue was correlated only with soil fluoranthene concentration and not with soil moisture content. Taken together these results suggest that the IA model can help interpret the joint effects of chemical and nonchemical stressors. Such analyses should, however, be done with caution since the literature data set suggests that there may be cases where interactions between stressors result in joint effects that differ significantly from IA predictions.

  19. Effectiveness of Non-pharmacological Interventions on Stereotyped and Repetitive Behaviors in Preschool Children With Autism: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Hadi Zarafshan

    2017-03-01

    Full Text Available Objective: The present study aimed to review the literature on non-pharmacological interventions used to treat stereotyped and repetitive behaviors by a systematic method. Methods: Two authors independently performed a search strategy on Medline/PubMed, Scopus and PsycINFO on English articles published up to April 23, 2014 with relevant search keywords. We also reviewed the bibliographies of retrieved articles and conference proceedings to obtain additional citations and references. We used those articles that address any non-pharmacological interventions on reducing stereotyped and repetitive behaviors in preschool children with autism. Four independent reviewers screened relevant articles for inclusion criteria and assessed the quality of eligible articles with CONSORT checklist. Results: In our search, 664 relevant articles were found. After removing duplicates and screening based on title, abstract, and full text, 15 high quality studies were finally included in data analyses. The included articles were published from 1987 to 2013. Three studies were designed as A-B, two as A-B-A and reminders as A-B-A-B. The data and results of 3 clinical trials were synthesized; two of them were parallel randomized clinical trial and another one was designed as cross-over. Interventions were completely heterogeneous in case studies, including non-contingent auditory stimulation, response interruption and redirection, teaching the children to request assistance on the difficult tasks, family-implemented treatment for behavioral inflexibility with treatment approach, vocal or motor response interruption and redirection, brushing, water mist treatment, exposure response prevention, tangible reinforcement or social reinforcement, and music. Interventions in clinical trials included touch therapy, kata techniques training program, and aerobic exercise. Conclusions: The results of our review indicate that different kinds of non-pharmacological interventions can

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

    Science.gov (United States)

    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.