WorldWideScience

Sample records for multiple pharmacological actions

  1. Pharmacologic treatment of depression in multiple sclerosis

    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

  2. Multiple sclerosis: general features and pharmacologic approach

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

    2009-01-01

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

  3. Pharmacological management of spasticity in multiple sclerosis

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

    2016-01-01

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

  4. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis

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

    2015-01-01

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

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

    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.

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

    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.

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

    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.

  8. Pharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis.

    Miller, Elzbieta; Morel, Agnieszka; Redlicka, Justyna; Miller, Igor; Saluk, Joanna

    2018-01-01

    Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to 65 percent of MS patients have cognitive deficits such as episodic memory, sustained attention, reduced verbal fluency; however, the cognitive MS domain is information processing speed. It is the first syndrome of cognitive dysfunction and the most widely affected in MS. Occasionally these impairments occur even before the appearance of physical symptoms. Therefore, this review focused on the current status of our knowledge about possible methods of treatment cognitive impairment in MS patients including novel strategies. Research and online content was performed using Medline and EMBASE databases. The most recent research suggests that cognitive impairment is correlated with brain lesion volume and brain atrophy. The examination of the cognitive impairment is usually based on particular neuropsychological batteries. However, it can be not enough to make a precise diagnosis. This creates a demand to find markers that might be useful for identifying patients with risk of cognitive impairment at an early stage of the disease. Currently the most promising methods consist of neuroimaging indicators, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Diagnosis problems are strictly connected with treatment procedures. There are two main cognitive therapies: pharmacological (disease modifying drugs (DMD), symptomatic treatments) and non-pharmacological interventions that are focused on psychological and physical rehabilitation. Some trials have shown a positive association between physical activity and the cognitive function. This article is an overview of the current state of knowledge related to cognition impairment treatment in MS. Additionally, novel strategies for cognitive impairments such as cryostimulation and other complementary methods are

  9. Pharmacological treatment for memory disorder in multiple sclerosis.

    He, Dian; Zhang, Yun; Dong, Shuai; Wang, Dongfeng; Gao, Xiangdong; Zhou, Hongyu

    2013-12-17

    This is an update of the Cochrane review "Pharmacologic treatment for memory disorder in multiple sclerosis" (first published in The Cochrane Library 2011, Issue 10).Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, demyelinating, neurodegenerative disorder of the central nervous system (CNS) and can cause both neurological and neuropsychological disability. Both demyelination and axonal and neuronal loss are believed to contribute to MS-related cognitive impairment. Memory disorder is one of the most frequent cognitive dysfunctions and presents a considerable burden to people with MS and to society due to the negative impact on function. A number of pharmacological agents have been evaluated in many existing randomised controlled trials for their efficacy on memory disorder in people with MS but the results were not consistent. To assess the absolute and comparative efficacy, tolerability and safety of pharmacological treatments for memory disorder in adults with MS. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Register (24 July 2013), PsycINFO (January 1980 to 26 June 2013) and CBMdisc (1978 to 24 June 2013), and checked reference lists of identified articles, searched some relevant journals manually, registers of clinical trials and published abstracts of conference proceedings. All double-blind, randomised controlled parallel trials on pharmacological treatment versus placebo or one or more pharmacological treatments in adults with MS who had at least mild memory impairment (at 0.5 standard deviations below age- and sex-based normative data on a validated memory scale). We placed no restrictions regarding dose, route of administration and frequency; however, we only included trials with an administration duration of 12 weeks or greater. Two review authors independently assessed trial quality and extracted data. We discussed disagreements and resolved them by consensus among review

  10. Multiple sclerosis: general features and pharmacologic approach; Esclerosis multiple: aspectos generales y abordaje farmacologico

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio [Instituto de Farmacia y Alimentos, Universidad de La Habana, La Habana (Cuba)

    2009-07-01

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

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

    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.

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

    Luca Masotti

    2013-12-01

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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

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

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

    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.

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

    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.

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

    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.

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

    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.

  6. Skeleton-based human action recognition using multiple sequence alignment

    Ding, Wenwen; Liu, Kai; Cheng, Fei; Zhang, Jin; Li, YunSong

    2015-05-01

    Human action recognition and analysis is an active research topic in computer vision for many years. This paper presents a method to represent human actions based on trajectories consisting of 3D joint positions. This method first decompose action into a sequence of meaningful atomic actions (actionlets), and then label actionlets with English alphabets according to the Davies-Bouldin index value. Therefore, an action can be represented using a sequence of actionlet symbols, which will preserve the temporal order of occurrence of each of the actionlets. Finally, we employ sequence comparison to classify multiple actions through using string matching algorithms (Needleman-Wunsch). The effectiveness of the proposed method is evaluated on datasets captured by commodity depth cameras. Experiments of the proposed method on three challenging 3D action datasets show promising results.

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

    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

  8. A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

    Xinkui Liu

    2018-01-01

    Full Text Available Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

  9. 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

    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

  10. Anesthetic pharmacology

    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...

  11. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

    Montalban, X; Gold, R; Thompson, A J; Otero-Romero, S; Amato, M P; Chandraratna, D; Clanet, M; Comi, G; Derfuss, T; Fazekas, F; Hartung, H P; Havrdova, E; Hemmer, B; Kappos, L; Liblau, R; Lubetzki, C; Marcus, E; Miller, D H; Olsson, T; Pilling, S; Selmaj, K; Siva, A; Sorensen, P S; Sormani, M P; Thalheim, C; Wiendl, H; Zipp, F

    2018-02-01

    Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at

  12. 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".

    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.

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

    Hui Wang

    2014-01-01

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

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

    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...

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

    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

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

    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

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

    Trailović Saša M.

    2010-01-01

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

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

    Jain S

    2017-03-01

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

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

    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.

  20. Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system

    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

  1. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

    Tobias Ruck

    2015-07-01

    Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

  2. 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

    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.

  3. Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

    Yang, Ting-Ting; Wang, Li; Deng, Xiao-Yang; Yu, Gang

    2017-09-15

    Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs. Copyright © 2017. Published by Elsevier B.V.

  4. Possibilities of pharmacologic correction of cognitive disorders in conditions of experimental equivalent of multiple sclerosis

    Nefyodov A.A.

    2015-06-01

    Full Text Available A comparative analysis of the impact of citicoline, ±-lipoic acid, nicergoline, donepezil and colloidal solution of nano-silver (CSNS on the processes of learning and consolidation of memorable track in the test of the conditional reaction of passive avoidance (CRPA in conditions of experimental allergic encephalomyelitis (EAE was conducted. Testing of passive defensive skill was performed on days 12 and 20 after the induction of EAE. To assess the impact of drugs on the inputted information processes the investigated substances were administered intragastrically (CSNS - intraperitoneally once daily in the definite dose from the second to the day 10 after the induction of EAE (latent phase of the disease, and assessing processes of conditional skill preserving, further administration of drugs by the day 20 of the experiment (average duration of EAE was used. A positive effect of citicoline, ±-lipoic acid, nicergoline and donepezil on the input information processes and the ability to prevent accelerated extinction of acquired contingent skill in the conditions of experimental pathology was established. Drugs statistically significantly increased duration of the latent period of CRPA in comparison with a group of active control by 49%, 43%, 39% and 34%, respectively. Here with preparations were characterized by a high coefficient of antiamnesic activity, by the end of the experiment it was recorded at the level of 95% (citicoline, 81% (±-lipoic acid, 76% (nicergoline and 53% (donepezil. It is shown that the ability to prevent development of cognitive impairment in conditions of experimental equivalent of multiple sclerosis decreases in the number of citicoline (500 mg/kg > ±-lipoic acid (50 mg/kg H nicergoline (10 mg/kg > donepezil (10 mg/kg.

  5. Structure Determination of Cisplatin-Amino Acid Analogues by Infrared Multiple Photon Dissociation Action Spectroscopy

    He, Chenchen; Bao, Xun; Zhu, Yanlong; Strobehn, Stephen; Kimutai, Bett; Nei, Y.-W.; Chow, C. S.; Rodgers, M. T.; Gao, Juehan; Oomens, J.

    2015-06-01

    To gain a better understanding of the binding mechanism and assist in the optimization of relevant drug and chemical probe design, both experimental and theoretical studies were performed on a series of amino acid-linked cisplatin derivatives, including glycine-, lysine-, and ornithine-linked cisplatin, Gplatin, Kplatin, and Oplatin, respectively. Cisplatin, the first FDA-approved platinum-based anticancer drug, has been widely used in cancer chemotherapy. Its pharmacological mechanism has been identified as its ability to coordinate to genomic DNA, and guanine is its major target. In previous reports, cisplatin was successfully utilized as a chemical probe to detect solvent accessible sites in ribosomal RNA (rRNA). Among the amino-acid-linked cisplatin derivatives, Oplatin exhibits preference for adenine over guanine. The mechanism behind its different selectivity compared to cisplatin may relate to its potential of forming a hydrogen bond between the carboxylate group in Pt (II) complex and the 6-amino moiety of adenosine stabilizes A-Oplatin products. Tandem mass spectrometry analysis also indicates that different coordination sites of Oplatin on adenosine affect glycosidic bond stability. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments were performed on all three amino acid-linked cisplatin to characterize their structures. An extensive theoretical study has been performed on Gplatin to guide the selection of the most effective theory and basis set based on its geometric information. The results for Gplatin provide the foundation for characterization of the more complex amino acid-linked cisplatin derivatives, Oplatin and Kplatin. Structural and energetic information elucidated for these compounds, particularly Oplatin reveal the reason for its alternative selectivity compared to cisplatin.

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

    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.

  7. Multiple Disabilities and Visual Impairment: An Action Research Project

    Argyropoulos, Vassilios; Thymakis, Paraskevas

    2014-01-01

    Children with visual and motor disabilities constitute a distinct group with a unique set of educational needs. Such children are often grouped with the broader population of children with multiple disabilities and visual impairments (that is, those who are blind or have low vision) (Erin, 2000; McLinden, 1997). The chief characteristic of…

  8. Esclerosis múltiple: aspectos generales y abordaje farmacológico Multiple sclerosis: general features and pharmacologic approach

    Nielsen Lagumersindez Denis

    2009-08-01

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

  9. Where and how to manage: optimal selection of conservation actions for multiple species

    Teeffelen, van A.J.A.; Moilanen, A.

    2008-01-01

    Multiple alternative options are frequently available for the protection, maintenance or restoration of conservation areas. The choice of a particular management action can have large effects on the species occurring in the area, because different actions have different effects on different species.

  10. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    Waldbusser, George G; Hales, Burke; Langdon, Chris J; Haley, Brian A; Schrader, Paul; Brunner, Elizabeth L; Gray, Matthew W; Miller, Cale A; Gimenez, Iria; Hutchinson, Greg

    2015-01-01

    Ocean acidification (OA) is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4) with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material affected only by

  11. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    George G Waldbusser

    Full Text Available Ocean acidification (OA is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4 with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material

  12. Identification of critical locations across multiple infrastructures for terrorist actions

    Patterson, S.A.; Apostolakis, G.E.

    2007-01-01

    This paper presents a possible approach to ranking geographic regions that can influence multiple infrastructures. Once ranked, decision makers can determine whether these regions are critical locations based on their susceptibility to terrorist acts. We identify these locations by calculating a value for a geographic region that represents the combined values to the decision makers of all the infrastructures crossing through that region. These values, as well as the size of the geographic region, are conditional on an assumed destructive threat of a given size. In our case study, the threat is assumed to be minor, e.g., a bomb that can affect objects within 7 m of it. This approach first requires an assessment of the users of the system. During this assessment, each user is assigned a performance index (PI) based on the disutility of the loss of each infrastructure's resource via multi-attribute utility theory (MAUT). A Monte Carlo network analysis is then performed to develop importance measures (IM) for the elements of each infrastructure for their ability to service each user. We combine the IMs with the user PIs to a value that we call valued worth (VW) for each infrastructure's elements independently. Then we use spatial analysis techniques within a geographic information system (GIS) to combine the VWs of each infrastructure's elements in a geographic area, conditional on the threat, into a total value we call geographic valued worth (GVW). The GVW is displayed graphically in the GIS system in a color scheme that shows the numerical ranking of these geographic areas. The map and rankings are then submitted to the decision makers to better allocate anti-terrorism resources. A case study of this methodology is performed on the Massachusetts Institute of Technology (MIT) campus. The results of the study show how the methodology can bring attention to areas that are important when several infrastructures are considered, but may be ignored when infrastructures

  13. Multiple emotions: a person-centered approach to the relationship between intergroup emotion and action orientation.

    Fernando, Julian W; Kashima, Yoshihisa; Laham, Simon M

    2014-08-01

    Although a great deal of research has investigated the relationship between emotions and action orientations, most studies to date have used variable-centered techniques to identify the best emotion predictor(s) of a particular action. Given that people frequently report multiple or blended emotions, a profitable area of research may be to adopt person-centered approaches to examine the action orientations elicited by a particular combination of emotions or "emotion profile." In two studies, across instances of intergroup inequality in Australia and Canada, we examined participants' experiences of six intergroup emotions: sympathy, anger directed at three targets, shame, and pride. In both studies, five groups of participants with similar emotion profiles were identified by cluster analysis and their action orientations were compared; clusters indicated that the majority of participants experienced multiple emotions. Each action orientation was also regressed on the six emotions. There were a number of differences in the results obtained from the person-centered and variable-centered approaches. This was most apparent for sympathy: the group of participants experiencing only sympathy showed little inclination to perform prosocial actions, yet sympathy was a significant predictor of numerous action orientations in regression analyses. These results imply that sympathy may only prompt a desire for action when experienced in combination with other emotions. We suggest that the use of person-centered and variable-centered approaches as complementary analytic strategies may enrich research into not only the affective predictors of action, but emotion research in general.

  14. Where and how to manage: Optimal selection of conservation actions for multiple species.

    Astrid van Teeffelen

    2008-01-01

    Full Text Available Multiple alternative options are frequently available for the protection, maintenance or restoration of conservation areas. The choice of a particular management action can have large effects on the species occurring in the area, because different actions have different effects on different species. Together with the fact that conservation funds are limited and particular management actions are costly, it would be desirable to be able to identify where, and what kind of management should be applied to maximize conservation benefits. Currently available site-selection algorithms can identify the optimal set of sites for a reserve network. However, these algorithms have not been designed to answer what kind of action would be most beneficial at these sites when multiple alternative actions are available. We describe an algorithm capable of solving multi-species planning problems with multiple management options per site. The algorithm is based on benefit functions, which translate the effect of a management action on species representation levels into a value, in order to identify the most beneficial option. We test the performance of this algorithm with simulated data for different types of benefit functions and show that the algorithm’s solutions are optimal, or very near globally optimal, partially depending on the type of benefit function used. The good performance of the proposed algorithm suggests that it could be profitably used for large multi-action multi-species conservation planning problems.

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

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

    1994-01-01

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

  16. A Limb Action Detector Enabling People with Multiple Disabilities to Control Environmental Stimulation through Limb Action with a Nintendo Wii Remote Controller

    Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

    2010-01-01

    This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using limb action with a Nintendo Wii Remote Controller and a newly developed limb action detection program (LADP, i.e., a new software program that turns a Wii Remote Controller into a precise limb action detector). This study was…

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

    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

  18. Exploring multiple intelligences theory in the context of science education: An action research approach

    Goodnough, Karen Catherine

    2000-10-01

    Since the publication of Frames of Mind: The Theory in Practice, multiple intelligences, theory (Gardner, 1983) has been used by practitioners in a variety of ways to make teaching and learning more meaningful. However, little attention has been focused on exploring the potential of the theory for science teaching and learning. Consequently, this research study was designed to: (1) explore Howard Gardner's theory of multiple intelligences (1983) and its merit for making science teaching and learning more meaningful; (2) provide a forum for teachers to engage in critical self-reflection about their theory and practice in science education; (3) study the process of action research in the context of science education; and (4) describe the effectiveness of collaborative action research as a framework for teacher development and curriculum development. The study reports on the experiences of four teachers (two elementary teachers, one junior high teacher, and one high school teacher) and myself, a university researcher-facilitator, as we participated in a collaborative action research project. The action research group held weekly meetings over a five-month period (January--May, 1999). The inquiry was a qualitative case study (Stake, 1994) that aimed to understand the perspectives of those directly involved. This was achieved by using multiple methods to collect data: audiotaped action research meetings, fieldnotes, semi-structured interviews, journal writing, and concept mapping. All data were analysed on an ongoing basis. Many positive outcomes resulted from the study in areas such as curriculum development, teacher development, and student learning in science. Through the process of action research, research participants became more reflective about their practice and thus, enhanced their pedagogical content knowledge (Shulman, 1987) in science. Students became more engaged in learning science, gained a greater understanding of how they learn, and experienced a

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

    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.

  20. Local Action Groups and Rural Sustainable Development. A spatial multiple criteria approach for efficient territorial planning

    Palmisano, Giovanni Ottomano; Govindan, M.E., PhD.,, Kannan; Boggia, Antonio

    2016-01-01

    Local Action Groups in order to promote the objectives of Rural Sustainable Development within rural municipalities. Each Local Action Group applies the Strengths, Weaknesses, Opportunities and Threats analysis in order to identify for its own rural municipalities the strategic elements to which...... and a Weakness factors and decision alternatives, as well as impossibility of ranking the decision alternatives. Thus, this research aims to overcome the drawbacks of the Strengths, Weaknesses, Opportunities and Threats analysis and to support Local Action Group partnerships in the sustainability evaluation...... of their rural municipalities, and therefore to aid the identification of a common Rural Sustainable Development strategy to allocate the European Agricultural Fund for Rural Development budget. This decision problem was tackled by applying a Multiple Criteria Spatial Decision Support System that integrates...

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

    Hadrup, Niels

    2014-08-01

    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.

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

    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.

  3. Pharmacological Effects of Biotin in Animals.

    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.

  4. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

    Amy ePerrin Ross

    2013-03-01

    Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

  5. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad

    2016-01-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied...... in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment....... Several probiotics have been characterized and applied in fish and a number of them are of host origin. Unlike some disease control alternatives being adapted and proposed in aquaculture where actions are unilateral, the immense potential of probiotics lies on their multiple mechanisms in conferring...

  6. CLINICAL PHARMACOLOGY OF DIURETICS

    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.

  7. Developmental paediatric anaesthetic pharmacology

    Hansen, Tom Giedsing

    2015-01-01

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

  8. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review.

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad; Tiwari, Ruchi; Karthik, K; Dhama, Kuldeep; Lazado, Carlo C

    2016-12-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment. Several probiotics have been characterized and applied in fish and a number of them are of host origin. Unlike some disease control alternatives being adapted and proposed in aquaculture where actions are unilateral, the immense potential of probiotics lies on their multiple mechanisms in conferring benefits to the host fish and the rearing environment. The staggering number of probiotics papers in aquaculture highlights the multitude of advantages from these microorganisms and conspicuously position them in the dynamic search for health-promoting alternatives for cultured fish. This paper provides an update on the use of probiotics in finfish aquaculture, particularly focusing on their modes of action. It explores the contemporary understanding of their spatial and nutritional competitiveness, inhibitory metabolites, environmental modification capability, immunomodulatory potential and stress-alleviating mechanism. This timely update affirms the importance of probiotics in fostering sustainable approaches in aquaculture and provides avenues in furthering its research and development.

  9. Status of safety issues at licensed power plants: TMI Action Plan requirements, unresolved safety issues, generic safety issues, other multiplant action issues

    1992-12-01

    This report is to provide a comprehensive description of the implementation and verification status of Three Mile Island (TMI) Action Plan requirements, safety issues designated as Unresolved Safety Issues (USIs), Generic Safety Issues(GSIs), and other Multiplant Actions (MPAs) that have been resolved and involve implementation of an action or actions by licensees. This report makes the information available to other interested parties, including the public. An additional purpose of this NUREG report is to serve as a follow-on to NUREG-0933, ''A Prioritization of Generic Safety Issues,'' which tracks safety issues up until requirements are approved for imposition at licensed plants or until the NRC issues a request for action by licensees

  10. A coarse-grained model for synergistic action of multiple enzymes on cellulose

    Asztalos Andrea

    2012-08-01

    Full Text Available Abstract Background Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates. Results We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose. Conclusions Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures

  11. Network-based Approaches in Pharmacology.

    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.

  12. Harnessing Big Data for Systems Pharmacology.

    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.

  13. The root hair assay facilitates the use of genetic and pharmacological tools in order to dissect multiple signalling pathways that lead to programmed cell death.

    Joanna Kacprzyk

    Full Text Available The activation of programmed cell death (PCD is often a result of complex signalling pathways whose relationship and intersection are not well understood. We recently described a PCD root hair assay and proposed that it could be used to rapidly screen genetic or pharmacological modulators of PCD. To further assess the applicability of the root hair assay for studying multiple signalling pathways leading to PCD activation we have investigated the crosstalk between salicylic acid, autophagy and apoptosis-like PCD (AL-PCD in Arabidopsis thaliana. The root hair assay was used to determine rates of AL-PCD induced by a panel of cell death inducing treatments in wild type plants treated with chemical modulators of salicylic acid synthesis or autophagy, and in genetic lines defective in autophagy or salicylic acid signalling. The assay demonstrated that PCD induced by exogenous salicylic acid or fumonisin B1 displayed a requirement for salicylic acid signalling and was partially dependent on the salicylic acid signal transducer NPR1. Autophagy deficiency resulted in an increase in the rates of AL-PCD induced by salicylic acid and fumonisin B1, but not by gibberellic acid or abiotic stress. The phenylalanine ammonia lyase-dependent salicylic acid synthesis pathway contributed only to death induced by salicylic acid and fumonisin B1. 3-Methyladenine, which is commonly used as an inhibitor of autophagy, appeared to influence PCD induction in all treatments suggesting a possible secondary, non-autophagic, effect on a core component of the plant PCD pathway. The results suggest that salicylic acid signalling is negatively regulated by autophagy during salicylic acid and mycotoxin-induced AL-PCD. However, this crosstalk does not appear to be directly involved in PCD induced by gibberellic acid or abiotic stress. This study demonstrates that the root hair assay is an effective tool for relatively rapid investigation of complex signalling pathways leading to

  14. Measurement with multiple indicators and psychophysical scaling in the context of Fishbein and Ajzen's theory of reasoned action

    van den Putte, B.; Saris, W.E.; Hoogstraten, J.

    1995-01-01

    Two experiments were carried out to test the theory of reasoned action of Fishbein and Ajzen. The measurements were done using two category scales and two psychophysical scales. No consistent difference in results was found between the four modalities. However, if the latter were used as multiple

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

    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.

  16. Status of safety issues at licensed power plants: TMI Action Plan requirements; unresolved safety issues; generic safety issues; other multiplant action issues

    1993-12-01

    As part of ongoing US Nuclear Regulatory Commission (NRC) efforts to ensure the quality and accountability of safety issue information, the NRC established a program for publishing an annual report on the status of licensee implementation and NRC verification of safety issues in major NRC requirements areas. This information was initially compiled and reported in three NUREG-series volumes. Volume 1, published in March 1991, addressed the status of Three Mile Island (TMI) Action Plan Requirements. Volume 2, published in May 1991, addressed the status of unresolved safety issues (USIs). Volume 3, published in June 1991, addressed the implementation and verification status of generic safety issues (GSIs). The first annual supplement, which combined these volumes into a single report and presented updated information as of September 30, 1991, was published in December 1991. The second annual supplement, which provided updated information as of September 30, 1992, was published in December 1992. Supplement 2 also provided the status of licensee implementation and NRC verification of other multiplant action (MPA) issues not related to TMI Action Plan requirements, USIs, or GSIs. This third annual NUREG report, Supplement 3, presents updated information as of September 30, 1993. This report gives a comprehensive description of the implementation and verification status of TMI Action Plan requirements, safety issues designated as USIs, GSIs, and other MPAs that have been resolved and involve implementation of an action or actions by licensees. This report makes the information available to other interested parties, including the public. Additionally, this report serves as a follow-on to NUREG-0933, ''A Prioritization of Generic Safety Issues,'' which tracks safety issues until requirements are approved for imposition at licensed plants or until the NRC issues a request for action by licensees

  17. Status of safety issues at licensed power plants: TMI Action Plan requirements, unresolved safety issues, generic safety issues, other multiplant action issues. Supplement 4

    1994-12-01

    As part of ongoing US Nuclear Regulatory Commission (NRC) efforts to ensure the quality and accountability of safety issue information, the NRC established a program for publishing an annual report on the status of licensee implementation and NRC verification of safety issues in major NRC requirements areas. This information was initially compiled and reported in three NUREG-series volumes. Volume 1, published in March 1991, addressed the status of Three Mile Island (TMI) Action Plan Requirements. Volume 2, published in May 1991, addressed the status of unresolved safety issues (USIs). Volume 3, published in June 1991, addressed the implementation and verification status of generic safety issues (GSIs). The first annual supplement, which combined these volumes into a single report and presented updated information as of September 30, 1991, was published in December 1991. The second annual supplement, which provided updated information as of September 30, 1992, was published in December 1992. Supplement 2 also provided the status of licensee implementation and NRC verification of other multiplant action (MPA) issues not related to TMI Action Plan requirements, USIs, or GSIs. Supplement 3 gives status as of September 30, 1993. This annual report, Supplement 4, presents updated information as of September 30, 1994. This report gives a comprehensive description of the implementation and verification status of TMI Action Plan requirements, safety issues designated as USIs, GSIs, and other MPAs that have been resolved and involve implementation of an action or actions by licensees. This report makes the information available to other interested parties, including the public. Additionally, this report serves as a follow-on to NUREG-0933, ''A Prioritization of Generic Safety Issues,'' which tracks safety issues until requirements are approved for imposition at licensed plants or until the NRC issues a request for action by licensees

  18. [Pharmacological treatment].

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Schoepp, D.D.; Ornstein, P.L.; Leander, J.D.; Lodge, D.; Salhoff, C.R.; Zeman, S.; Zimmerman, D.M.

    1990-01-01

    This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity

  20. Multiple Competences of Judicial and Social Intervention: Portuguese Public Prosecutors in Action

    João Paulo Dias

    2017-10-01

    Full Text Available Public Prosecutors have not received much attention from international, suprastate, state and/or associative institutions in terms of seeking to influence the adoption of a common organisational model by the most diverse countries. What we have instead is mainly the approval, at different moments, of guiding principles for the exercise of functions—primarily of judges, but also, since the late 1980s, of Public Prosecutors—with special emphasis on issues of autonomy and impartiality regarding their competences and the conditions in which prosecution is carried out. However, in countries such as Portugal, Public Prosecutors exercise a wide range of competences in various legal areas, a fact that turns them into key actors in a context of evaluating the performance of the judicial system and when efforts are being made to improve its functioning, even in the midst of financial constraints. This is the backdrop to the present article, which stems from the need to discuss the functioning of the Public Prosecution Service and its professional practices in order to promote the circulation of ideas and solutions for possible judicial reforms in the model currently in force in Portugal. It is not a question of looking for the “perfect model” or of trying to achieve an “ideal synthesis,” but rather of highlighting the main aspects that can contribute to the defence of legality and the promotion of access to law and justice through the action of Public Prosecutors. In order to achieve such a goal, it is necessary for Public Prosecutors to assume a new paradigm, centred on the defence of citizenship rights. The main objective here is to discuss and reflect on the identity, competences and professional practice of Portugal’s Public Prosecutors in the context of major transformations in the judicial systems and in the legal professions themselves, both as key actors and as promoters of citizens' access to law and justice in the various legal

  1. Pharmacological Profile of Quinoxalinone

    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.

  2. Pharmacological effects of biotin.

    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.

  3. A study on the dependency evaluation for multiple human actions in human reliability analysis of probabilistic safety assessment

    Kang, D. I.; Yang, J. E.; Jung, W. D.; Sung, T. Y.; Park, J. H.; Lee, Y. H.; Hwang, M. J.; Kim, K. Y.; Jin, Y. H.; Kim, S. C.

    1997-02-01

    This report describes the study results on the method of the dependency evaluation and the modeling, and the limited value of human error probability (HEP) for multiple human actions in accident sequences of probabilistic safety assessment (PSA). THERP and Parry's method, which have been generally used in dependency evaluation of human reliability analysis (HRA), are introduced and their limitations are discussed. New dependency evaluation method in HRA is established to make up for the weak points of THERP and Parry's methods. The limited value of HEP is also established based on the review of several HRA related documents. This report describes the definition, the type, the evaluation method, and the evaluation example of dependency to help the reader's understanding. It is expected that this study results will give a guidance to HRA analysts in dependency evaluation of multiple human actions and enable PSA analysts to understand HRA in detail. (author). 23 refs., 3 tabs., 2 figs

  4. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  5. Recent Pharmacology Studies on the International Space Station

    Wotring, Virginia

    2014-01-01

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

  6. Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

    Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

    2016-01-01

    Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

  7. Enumeration versus Multiple Object Tracking: The Case of Action Video Game Players

    Green, C. S.; Bavelier, D.

    2006-01-01

    Here, we demonstrate that action video game play enhances subjects' ability in two tasks thought to indicate the number of items that can be apprehended. Using an enumeration task, in which participants have to determine the number of quickly flashed squares, accuracy measures showed a near ceiling performance for low numerosities and a sharp drop…

  8. Infants Prospectively Control Reaching Based on the Difficulty of Future Actions: To What Extent Can Infants' Multiple-Step Actions Be Explained by Fitts' Law?

    Gottwald, Janna M.; De Bortoli Vizioli, Aurora; Lindskog, Marcus; Nyström, Pär; L. Ekberg, Therese; von Hofsten, Claes; Gredebäck, Gustaf

    2017-01-01

    Prospective motor control, a key element of action planning, is the ability to adjust one's actions with respect to task demands and action goals in an anticipatory manner. The current study investigates whether 14-month-olds can prospectively control their reaching actions based on the difficulty of the subsequent action. We used a reach-to-place…

  9. Automated optimal coordination of multiple-DOF neuromuscular actions in feedforward neuroprostheses.

    Lujan, J Luis; Crago, Patrick E

    2009-01-01

    This paper describes a new method for designing feedforward controllers for multiple-muscle, multiple-DOF, motor system neural prostheses. The design process is based on experimental measurement of the forward input/output properties of the neuromechanical system and numerical optimization of stimulation patterns to meet muscle coactivation criteria, thus resolving the muscle redundancy (i.e., overcontrol) and the coupled DOF problems inherent in neuromechanical systems. We designed feedforward controllers to control the isometric forces at the tip of the thumb in two directions during stimulation of three thumb muscles as a model system. We tested the method experimentally in ten able-bodied individuals and one patient with spinal cord injury. Good control of isometric force in both DOFs was observed, with rms errors less than 10% of the force range in seven experiments and statistically significant correlations between the actual and target forces in all ten experiments. Systematic bias and slope errors were observed in a few experiments, likely due to the neuromuscular fatigue. Overall, the tests demonstrated the ability of a general design approach to satisfy both control and coactivation criteria in multiple-muscle, multiple-axis neuromechanical systems, which is applicable to a wide range of neuromechanical systems and stimulation electrodes.

  10. Multiple Site Action Research Case Studies: Practical and Theoretical Benefits and Challenges

    Pereira, Mary Delfin; Vallance, Roger

    2006-01-01

    A curriculum initiative project was implemented in four schools in Singapore over a span of five to six weeks during 2004. The project employed a number of different schools: girls only, boys only and co-educational schools; different levels of performance in a graded situation; multiple teachers and classes within each site; and control and…

  11. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

    Volvert, Marie-Laure; Seyen, Sandrine; Piette, Marie; Evrard, Brigitte; Gangolf, Marjorie; Plumier, Jean-Christophe; Bettendorff, Lucien

    2008-06-12

    after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.

  12. Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses.

    Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z

    2016-11-02

    Stress influences memory, an adaptive process crucial for survival. During stress, hippocampal synapses are bathed in a mixture of stress-released molecules, yet it is unknown whether or how these interact to mediate the effects of stress on memory. Here, we demonstrate novel synergistic actions of corticosterone and corticotropin-releasing hormone (CRH) on synaptic physiology and dendritic spine structure that mediate the profound effects of acute concurrent stresses on memory. Spatial memory in mice was impaired enduringly after acute concurrent stresses resulting from loss of synaptic potentiation associated with disrupted structure of synapse-bearing dendritic spines. Combined application of the stress hormones corticosterone and CRH recapitulated the physiological and structural defects provoked by acute stresses. Mechanistically, corticosterone and CRH, via their cognate receptors, acted synergistically on the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Accordingly, blocking the receptors of both hormones, but not each alone, rescued memory. Therefore, the synergistic actions of corticosterone and CRH at hippocampal synapses underlie memory impairments after concurrent and perhaps also single, severe acute stresses, with potential implications to spatial memory dysfunction in, for example, posttraumatic stress disorder. Stress influences memory, an adaptive process crucial for survival. During stress, adrenal corticosterone and hippocampal corticotropin-releasing hormone (CRH) permeate memory-forming hippocampal synapses, yet it is unknown whether (and how) these hormones interact to mediate effects of stress. Here, we demonstrate novel synergistic actions of corticosterone and CRH on hippocampal synaptic plasticity and spine structure that mediate the memory-disrupting effects of stress. Combined application of both hormones provoked synaptic function collapse and spine disruption

  13. Efficacy and immunological actions of FAHF-2 in a murine model of multiple food allergies.

    Srivastava, Kamal D; Bardina, Ludmilla; Sampson, Hugh A; Li, Xiu-Min

    2012-05-01

    Food Allergy Herbal Formula-2 (FAHF-2) prevents anaphylaxis in a murine model of peanut allergy. Multiple food allergies (MFA) are common and associated with a higher risk of anaphylaxis. No well-characterized murine model of sensitization to multiple food allergens exists, and no satisfactory therapy for MFA is currently available. To determine the effect of FAHF-2 in a murine model of MFA. C3H/HeJ mice were orally sensitized to peanut, codfish, and egg concurrently. Oral FAHF-2 treatment commenced 1 day after completing sensitization and continued daily for 7 weeks. Mice were subsequently orally challenged with each allergen. Antibodies in sera from mice simultaneously sensitized with peanut, codfish, and egg recognized major allergens of all 3 foods, demonstrating sensitization to multiple unrelated food allergens (MFA mice). Sham-treated MFA mice exhibited anaphylactic symptoms accompanied by elevation of plasma histamine and hypothermia. In contrast, FAHF-2-treated MFA mice showed no anaphylactic symptoms, normal body temperature, and histamine levels after challenge with each allergen. Protection was accompanied by reduction in allergen-specific immunoglobulin E levels. Allergen-stimulated Th2 cytokine interleukin-4 and interleukin-13 production levels decreased, whereas the Th1 cytokine interferon-γ levels were elevated in cultured splenocytes and mesenteric lymph node cells in FAHF-2-treated mice. We established the first murine model of MFA. FAHF-2 prevents peanut, egg, and fish-induced anaphylactic reactions in this model, suggesting that FAHF-2 may have potential for treating human MFA. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Sarmentine, a natural herbicide from Piper species with multiple herbicide mechanisms of action

    Franck Emmanuel Dayan

    2015-04-01

    Full Text Available Sarmentine, 1-(1-pyrrolidinyl-(2E,4E-2,4-decadien-1-one, is a natural amide isolated from the fruits of Piper species. The compound has a number of interesting biological properties, including its broad-spectrum activity on weeds as a contact herbicide. Initial studies highlighted a similarity in response between plants treated with sarmentine and herbicidal soaps such as pelargonic acid (nonanoic acid. However, little was known about the mechanism of action leading to the rapid desiccation of foliage treated by sarmentine. In cucumber cotyledon disc-assays, sarmentine induced rapid light-independent loss of membrane integrity at 100 µM or higher concentration, whereas 3 mM pelargonic acid was required for a similar effect. Sarmentine was between 10 and 30 times more active than pelargonic acid on wild mustard, velvetleaf, redroot pigweed and crabgrass. Additionally, the potency of 30 µM sarmentine was greatly stimulated by light, suggesting that this natural product may also interfere with photosynthetic processes. This was confirmed by observing a complete inhibition of photosynthetic electron transport at that concentration. Sarmentine also acted as an inhibitor of photosystem II on isolated thylakoid membranes by competing for the binding site of plastoquinone. This can be attributed in part to structural similarities between herbicides like sarmentine and diuron. While this mechanism of action accounts for the light stimulation of the activity of sarmentine, it does not account for its ability to destabilize membranes in darkness. In this respect, sarmentine has some structural similarity to crotonoyl-CoA, the substrate of enoyl-ACP reductase, a key enzyme in the early steps of fatty acid synthesis. Inhibitors of this enzyme, such as triclosan, cause rapid loss of membrane integrity in the dark. Sarmentine inhibited the activity of enoyl-ACP reductase, with an I50app of 18.3 µM. Therefore, the herbicidal activity of sarmentine appears to

  15. A pharmacologic study on the mechanism of action of Kakkon-to: body temperature elevation and phagocytic activation of macrophages in dogs.

    Muraoka, Kenichi; Yoshida, Satoshi; Hasegawa, Kazumasa; Nakanishi, Nobuo; Fukuzawa, Isao; Tomita, Akio; Cyong, Jong Chol

    2004-10-01

    The phagocytic activity of macrophages as a novel approach to scientific elucidation of the effects of Chinese medicines was studied through administration of a kampo preparation, by measuring the rise in body temperature, which is thought to stimulate innate defensive functions of organisms and enhance the immune systems. Using dogs as experimental models, a rise in body temperature following administration of Kakkon-to was observed, and the average number and average rate of phagocytosis of macrophages in blood using latex micro-particles was investigated. The body temperature of the treated animals significantly increased 30 minutes after administration (ptemperatures before and after administration showed significant increases over controls from 1 to 11 hours, ptemperature but also enhances the phagocytic activity of macrophages, an in vivo defense mechanism, suggesting that Kakkon-to contributes to the suppression of multiplication of common cold viruses and influenza viruses, which consequently results in improvement of various symptoms during infection with common cold viruses.

  16. Infrared multiple photon dissociation action spectroscopy of alkali metal cation-cyclen complexes: Effects of alkali metal cation size on gas-phase conformation

    Austin, C.A.; Chen, Y.; Kaczan, C.M.; Berden, G.; Oomens, J.; Rodgers, M.T.

    2013-01-01

    The gas-phase structures of alkali metal cationized complexes of cyclen (1,4,7,10-tetraazacyclododecane) are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and electronic structure theory calculations. The measured IRMPD action spectra of four M+(cyclen) complexes are

  17. Pharmacological Effects of Niacin on Acute Hyperlipemia.

    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.

  18. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

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

    Caroline Addison Carvalho Xavier

    2008-01-01

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

  20. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  1. Building a multiple modality, theory-based physical activity intervention: The development of CardiACTION!

    Estabrooks, Paul A; Glasgow, Russ E; Xu, Stan; Dzewaltowski, David A; Lee, Rebecca E; Thomas, Deborah; Almeida, Fabio A; Thayer, Amy N; Smith-Ray, Renae L

    2011-01-01

    OBJECTIVES: Despite the widely acknowledged benefits of regular physical activity (PA), specific goals for increased population levels of PA, and strongly recommended strategies to promote PA, there is no evidence suggesting that the prevalence of PA is improving. If PA intervention research is to be improved, theory should be used as the basis for intervention development, participant context or environment should be considered in the process, and intervention characteristics that will heighten the likelihood of translation into practice should be implemented (e.g., ease of implementation, low human resource costs). The purpose of this paper is to describe the implementation of the aforementioned concepts within the intervention development process associated with CardiACTION an ongoing randomized 2 × 2 factorial trial. METHODS: The Ecological Model of Physical Activity integrated with Protection Motivation Theory was used to inform the design of the interventions. This integrated model was selected to allow for the development of theory-based individual, environmental, and individually + environmentally targeted physical activity interventions. All intervention strategies were matched to proposed mediators of behavior change. Strategies were then matched to the most appropriate interactive technology (i.e., interactive computer session, automated telephone counseling, and tailored mailings) delivery channel. CONCLUSIONS: The potential implications of this study include determining the independent and combined influence of individual and environment mechanisms of behavior change on intervention effectiveness. In addition, all intervention models are developed to be scalable and disseminable to a broad audience at a low cost.

  2. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

    Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

    2017-12-01

    Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

  3. EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

    A. B. Dzheliya

    2015-01-01

    Full Text Available This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta. The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker, serum antibodies (IgM, IgG, IgA and IgE level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.

  4. arXiv Bose enhancement, the Liouville effective action and the high multiplicity tail in p-A collisions

    Kovner, Alex

    In the framework of dense-dilute CGC approach we study fluctuations in the multiplicity of produced particles in p-A collisions. We show that the leading effect that drives the fluctuations is the Bose enhancement of gluons in the proton wave function. We explicitly calculate the moment generating function that resums the effects of Bose enhancement. We show that it can be understood in terms of the Liouville effective action for the composite field which is identified with the fluctuating density, or saturation momentum of the proton. The resulting probability distribution turns out to be very close to the gamma-distribution. We also calculate the first correction to this distribution which is due to pairwise Hanbury Brown-Twiss correlations of produced gluons.

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

    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. Managing multiple diffuse pressures on water quality and ecological habitat: Spatially targeting effective mitigation actions at the landscape scale.

    Joyce, Hannah; Reaney, Sim

    2015-04-01

    Catchment systems provide multiple benefits for society, including: land for agriculture, climate regulation and recreational space. Yet, these systems also have undesirable externalities, such as flooding, and the benefits they create can be compromised through societal use. For example, agriculture, forestry and urban land use practices can increase the export of fine sediment and faecal indicator organisms (FIO) delivered to river systems. These diffuse landscape pressures are coupled with pressures on the in stream temperature environment from projected climate change. Such pressures can have detrimental impacts on water quality and ecological habitat and consequently the benefits they provide for society. These diffuse and in-stream pressures can be reduced through actions at the landscape scale but are commonly tackled individually. Any intervention may have benefits for other pressures and hence the challenge is to consider all of the different pressures simultaneously to find solutions with high levels of cross-pressure benefits. This research presents (1) a simple but spatially distributed model to predict the pattern of multiple pressures at the landscape scale, and (2) a method for spatially targeting the optimum location for riparian woodland planting as mitigation action against these pressures. The model follows a minimal information requirement approach along the lines of SCIMAP (www.scimap.org.uk). This approach defines the critical source areas of fine sediment diffuse pollution, rapid overland flow and FIOs, based on the analysis of the pattern of the pressure in the landscape and the connectivity from source areas to rivers. River temperature was modeled using a simple energy balance equation; focusing on temperature of inflowing and outflowing water across a catchment. The model has been calibrated using a long term observed temperature record. The modelling outcomes enabled the identification of the severity of each pressure in relative rather

  7. Multiple Intelligences in Action.

    Campbell, Bruce

    1992-01-01

    Describes the investigation of the effects of a four-step model program used with third through fifth grade students to implement Gardener's concepts of seven human intelligences--linguistic, logical/mathematical, visual/spatial, musical, kinesthetic, intrapersonal, and interpersonal intelligence--into daily learning. (BB)

  8. Pharmacology of midazolam.

    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.

  9. The Health Action Process Approach as a motivational model for physical activity self-management for people with multiple sclerosis: a path analysis.

    Chiu, Chung-Yi; Lynch, Ruth T; Chan, Fong; Berven, Norman L

    2011-08-01

    To evaluate the Health Action Process Approach (HAPA) as a motivational model for physical activity self-management for people with multiple sclerosis (MS). Quantitative descriptive research design using path analysis. One hundred ninety-five individuals with MS were recruited from the National Multiple Sclerosis Society and a neurology clinic at a university teaching hospital in the Midwest. Outcome was measured by the Physical Activity Stages of Change Instrument, along with measures for nine predictors (severity, action self-efficacy, outcome expectancy, risk perception, perceived barriers, intention, maintenance self-efficacy, action and coping planning, and recovery self-efficacy). The respecified HAPA physical activity model fit the data relatively well (goodness-of-fit index = .92, normed fit index = .91, and comparative fit index = .93) explaining 38% of the variance in physical activity. Recovery self-efficacy, action and coping planning, and perceived barriers directly contributed to the prediction of physical activity. Outcome expectancy significantly influenced intention and the relationship between intention and physical activity is mediated by action and coping planning. Action self-efficacy, maintenance self-efficacy, and recovery self-efficacy directly or indirectly affected physical activity. Severity of MS and action self-efficacy had an inverse relationship with perceived barriers and perceived barriers influenced physical activity. Empirical support was found for the proposed HAPA model of physical activity for people with MS. The HAPA model appears to provide useful information for clinical rehabilitation and health promotion interventions.

  10. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  11. Capture-based next-generation sequencing reveals multiple actionable mutations in cancer patients failed in traditional testing.

    Xie, Jing; Lu, Xiongxiong; Wu, Xue; Lin, Xiaoyi; Zhang, Chao; Huang, Xiaofang; Chang, Zhili; Wang, Xinjing; Wen, Chenlei; Tang, Xiaomei; Shi, Minmin; Zhan, Qian; Chen, Hao; Deng, Xiaxing; Peng, Chenghong; Li, Hongwei; Fang, Yuan; Shao, Yang; Shen, Baiyong

    2016-05-01

    Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10 years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next-generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput. We developed and validated a NGS-based cancer genomic diagnosis targeting 115 prognosis and therapeutics relevant genes on multiple specimen including blood, tumor tissue, and body fluid from 10 patients with different cancer types. The sequencing data was then analyzed by the clinical-applicable analytical pipelines developed in house. We have assessed analytical sensitivity, specificity, and accuracy of the NGS-based molecular diagnosis. Also, our developed analytical pipelines were capable of detecting base substitutions, indels, and gene copy number variations (CNVs). For instance, several actionable mutations of EGFR,PIK3CA,TP53, and KRAS have been detected for indicating drug susceptibility and resistance in the cases of lung cancer. Our study has shown that NGS-based molecular diagnosis is more sensitive and comprehensive to detect genomic alterations in cancer, and supports a direct clinical use for guiding targeted therapy.

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

    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.

  13. Gaultheria: Phytochemical and Pharmacological Characteristics

    Ren-Bing Shi

    2013-09-01

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

  14. The Health Action Process Approach as a Motivational Model of Dietary Self-Management for People with Multiple Sclerosis: A Path Analysis

    Chiu, Chung-Yi; Lynch, Ruth Torkelson; Chan, Fong; Rose, Lindsey

    2012-01-01

    The main objective of this study was to evaluate the health action process approach (HAPA) as a motivational model for dietary self-management for people with multiple sclerosis (MS). Quantitative descriptive research design using path analysis was used. Participants were 209 individuals with MS recruited from the National MS Society and a…

  15. Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

    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.

  16. Synergistic and independent actions of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs in Arabidopsis.

    Xiaoyan Wang

    2015-04-01

    Full Text Available All types of small RNAs in plants, piwi-interacting RNAs (piRNAs in animals and a subset of siRNAs in Drosophila and C. elegans are subject to HEN1 mediated 3' terminal 2'-O-methylation. This modification plays a pivotal role in protecting small RNAs from 3' uridylation, trimming and degradation. In Arabidopsis, HESO1 is a major enzyme that uridylates small RNAs to trigger their degradation. However, U-tail is still present in null hen1 heso1 mutants, suggesting the existence of (an enzymatic activities redundant with HESO1. Here, we report that UTP: RNA uridylyltransferase (URT1 is a functional paralog of HESO1. URT1 interacts with AGO1 and plays a predominant role in miRNA uridylation when HESO1 is absent. Uridylation of miRNA is globally abolished in a hen1 heso1 urt1 triple mutant, accompanied by an extensive increase of 3'-to-5' trimming. In contrast, disruption of URT1 appears not to affect the heterochromatic siRNA uridylation. This indicates the involvement of additional nucleotidyl transferases in the siRNA pathway. Analysis of miRNA tailings in the hen1 heso1 urt1 triple mutant also reveals the existence of previously unknown enzymatic activities that can add non-uridine nucleotides. Importantly, we show HESO1 may also act redundantly with URT1 in miRNA uridylation when HEN1 is fully competent. Taken together, our data not only reveal a synergistic action of HESO1 and URT1 in the 3' uridylation of miRNAs, but also independent activities of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs and an antagonistic relationship between uridylation and trimming. Our results may provide further insight into the mechanisms of small RNA 3' end modification and stability control.

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

    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.

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

    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

  19. Biological and Pharmacological properties

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

  20. Learning by observing: the effect of multiple sessions of action-observation training on the spontaneous movement tempo and motor resonance.

    Lagravinese, Giovanna; Bisio, Ambra; Ruggeri, Piero; Bove, Marco; Avanzino, Laura

    2017-02-01

    The present study was designed to explore the changes in motor performance and motor resonance after multiple sessions of action observation (AO) training. Subjects were exposed to the observation of a video showing finger tapping movements executed at 3Hz, a frequency higher than the spontaneous one (2Hz) for four consecutive days. Motor performance and motor resonance were tested before the AO training on the first day, and on the last day. Results showed that multiple sessions of AO training induced a shift of the speed of execution of finger tapping movements toward the observed one and a change in motor resonance. Before the 3Hz-AO training cortical excitability was highest during the observation of the 2Hz video. This motor resonance effect was lost after one single session of 3Hz-AO training whereas after multiple sessions of 3Hz-AO training cortical excitability was highest during the observation of the 3Hz video. Our study shows for the first time that multiple sessions of AO training are able not only to induce performance gains but also to change the way by which the observer's motor system recognizes a certain movement as belonging to the individual motor repertoire. These results may encourage the development of novel rehabilitative protocols based on multiple sessions of action observation aimed to regain a correct movement when its spontaneous speed is modified by pathologies or to modify the innate temporal properties of certain movements. Copyright © 2017. Published by Elsevier Ltd.

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

    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

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

    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.

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

    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

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

    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).

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

    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.

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

    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.

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

    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

  8. Combined chemical (fluoranthene) and drought effects on Lumbricus rubellus demonstrate the applicability of the independent action model for multiple stressor assessment.

    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.

  9. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H.; Raorane, Manish L.; Longkumer, Toshisangba; Pabuayon, Isaiah M.; Mutte, Sumanth K.; Vardarajan, Adithi R.; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C.; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor ‘no apical meristem’ (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  10. Pharmacological interventions to treat phlebitis: systematic review.

    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.

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

    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. Cardiovascular Safety Pharmacology of Sibutramine.

    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.

  13. Pharmacological interactions of vasoconstrictors.

    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.

  14. Carotenoids: biochemistry, pharmacology and treatment.

    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.

  15. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Verónica García-Alonso

    Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

  16. After Action Report:Idaho National Laboratory (INL) 2014 Multiple Facility Beyond Design Basis (BDBE) Evaluated Drill October 21, 2014

    Barnes, V. Scott [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-12-01

    On October 21, 2014, Idaho National Laboratory (INL), in coordination with local jurisdictions, and Department of Energy (DOE) Idaho Operations Office (DOE ID) conducted an evaluated drill to demonstrate the ability to implement the requirements of DOE O 151.1C, “Comprehensive Emergency Management System” when responding to a beyond design basis event (BDBE) scenario as outlined in the Office of Health, Safety, and Security Operating Experience Level 1 letter (OE-1: 2013-01). The INL contractor, Battelle Energy Alliance, LLC (BEA), in coordination with CH2M-WG Idaho, LLC (CWI), and Idaho Treatment Group LLC (ITG), successfully demonstrated appropriate response measures to mitigate a BDBE event that would impact multiple facilities across the INL while protecting the health and safety of personnel, the environment, and property. Offsite response organizations participated to demonstrate appropriate response measures.

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

    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. Ethnobotany, phytochemistry, and pharmacology of the genus Litsea: An update.

    Wang, Yun-Song; Wen, Zheng-Qi; Li, Bi-Tao; Zhang, Hong-Bin; Yang, Jing-Hua

    2016-04-02

    The genus Litsea is one of the most diverse genera of evergreen trees or shrubs belong to Lauraceae, and comprises roughly 400 species of tree that are distributed abundantly throughout tropical and subtropical Asia, North and South America. Litsea species have been used globally in traditional medicine for the treatment of various diseases including influenza, stomach aches, diarrhea, diabetes, vomiting, bone pain, inflammation, illness related to the central nervous system and other ailments. The purpose of this review is to provide updated, comprehensive and categorized information on the ethnobotany, phytochemistry and pharmacological research of Litsea species in order to explore their therapeutic potential and evaluate future research opportunities. All the available information on Litsea species was actualised by systematically searching the scientific literatures including Chinese, Korean, Japanese, Indian, and South American herbal classics, library catalogs and scientific databases (PubMed, SciFinder, Web of Science, Google Scholar, VIP and Wanfang). The Plant List, International Plant Name index and Scientific Database of China Plant Species were used to validate scientific names. 407 secondary metabolites have been reported from Litsea species. Litsea Species are sources of secondary metabolites with interesting chemical structures (alkaloids, lactones, sesquiterpenes, flavonoids, lignans, and essential oils) and significant bioactivities. Crude extracts, fractions and phytochemical constituents isolated from Litsea show a wide spectrum of in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, antimicrobial, antioxidant, antidiabetic, anti-HIV, insecticidal, etc. From data collected in this review, the genus Litsea comprises a wide range of therapeutically promising and valuable plants, and has attracted much attention owing to its multiple functions. Many traditional uses of Litsea species have now been validated by

  19. Pharmacology and function of melatonin receptors

    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

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

    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.

  1. Trials of Pharmacological Interventions for Tourette Syndrome: A Systematic Review

    Karen Waldon

    2013-01-01

    Full Text Available Introduction: Gilles de la Tourette Syndrome (GTS is a childhood-onset hyperkinetic movement disorder defined by the chronic presence of multiple motor tics and at least one vocal tic and often complicated by co-morbid behavioural problems. The pharmacological treatment of GTS focuses on the modulation of monoaminergic pathways within the cortico-striato-thalamo-cortical circuitry. This paper aims to evaluate the efficacy and safety profiles of pharmacological agents used in the treatment of tics in patients with GTS, in order to provide clinicians with an evidence-based rationale for the pharmacological treatment in GTS.

  2. [History and pharmacology of trazodone].

    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.

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

    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.

  4. Pharmacological Fingerprints of Contextual Uncertainty.

    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.

  5. Pharmacological modification of multi-drug resistance (MDR) in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin A and verapamil on MDR leukemia T-cells.

    Larsson, R; Nygren, P

    1990-07-15

    A novel fluorometric microculture cytotoxicity assay (FMCA), based on measurements of fluorescein diacetate (FDA) hydrolysis and DNA staining by Hoechst 33342, was used for drug sensitivity testing and detection of resistance reversal in acute lymphoblastic leukemia (ALL) cell lines. The 72-hr assay was found to be sensitive, reproducible and linearly related to the number of viable cells within a broad range of cell concentrations. At clinically achievable drug concentrations, the calcium channel blocker Verapamil (ver) and the immunosuppressant Cyclosporin A (csA) were found to partly reverse acquired Vincristine (vcr) resistance in multi-drug resistant (MDR) T-ALL L100 cells with little or no effect on the drug-sensitive parental L0 cell line. By combining the fluorometric indices, we found that low concentrations of csA were growth-inhibitory, whereas higher concentrations (greater than 10 micrograms/ml) were progressively cytotoxic for drug-sensitive L0 cells. In MDR L100 cells, on the other hand, csA produced significant cell kill even at low drug concentrations. Ver had no effects on sensitive L0 cells but showed considerable cytotoxic action towards MDR L100 cells. There was no apparent relationship between drug reversal of vcr resistance and the cytotoxic actions of the drug per se since the calcium channel blocker diltiazem (dil) significantly potentiated the actions of vcr on MDR L100 cells without being more toxic to these cells (compared to vcr-sensitive L0 cells).

  6. Effective actions and topological strings. Off-shell mirror symmetry and mock modularity of multiple M5-branes

    Hecht, Michael

    2011-01-01

    This thesis addresses two different topics within the field of string theory. In the first part it is shown how Hodge-theoretic methods in conjunction with open string mirror symmetry can be used to compute non-perturbative effective superpotential couplings for type II/F-theory compactifications with D-branes and fluxes on compact Calabi-Yau manifolds. This is achieved by studying the at structure of operators which derives from the open/closed Β-model geometry. We analyze the variation of mixed Hodge structure of the relative cohomology induced by a family of divisors, which is wrapped by a D7-brane. This leads to a Picard-Fuchs system of differential operators, which can be used to compute the moduli dependence of the superpotential couplings as well as the mirror maps at various points in the open/closed deformation space. These techniques are used to obtain predictions for genuine A-model Ooguri-Vafa invariants of special Lagrangian submanifolds in compact Calabi-Yau geometries and real enumerative invariants of on-shell domain wall tensions. By an open/closed duality the system of differential equations can also be obtained from a gauged linear σ-model, which describes a non-compact Calabi-Yau four-fold compactification without branes. This is used in the examples of multi-parameter models to study the various phases of the combined open/closed deformation space. It is furthermore shown how the brane geometry can be related to a F-theory compactification on a compact Calabi-Yau four-fold, where the Hodge-theoretic techniques can be used to compute the G-flux induced Gukov-Vafa-Witten potential. The dual F-theory picture also allows to conjecture the form of the Kaehler potential on the full open/closed deformation space. In the second part we analyze the background dependence of theories which derive from multiple wrapped M5-branes. Using the Kontsevich-Soibelman wall-crossing formula and the theory of mock modular forms we derive a holomorphic anomaly

  7. Effective actions and topological strings. Off-shell mirror symmetry and mock modularity of multiple M5-branes

    Hecht, Michael

    2011-10-20

    This thesis addresses two different topics within the field of string theory. In the first part it is shown how Hodge-theoretic methods in conjunction with open string mirror symmetry can be used to compute non-perturbative effective superpotential couplings for type II/F-theory compactifications with D-branes and fluxes on compact Calabi-Yau manifolds. This is achieved by studying the at structure of operators which derives from the open/closed {beta}-model geometry. We analyze the variation of mixed Hodge structure of the relative cohomology induced by a family of divisors, which is wrapped by a D7-brane. This leads to a Picard-Fuchs system of differential operators, which can be used to compute the moduli dependence of the superpotential couplings as well as the mirror maps at various points in the open/closed deformation space. These techniques are used to obtain predictions for genuine A-model Ooguri-Vafa invariants of special Lagrangian submanifolds in compact Calabi-Yau geometries and real enumerative invariants of on-shell domain wall tensions. By an open/closed duality the system of differential equations can also be obtained from a gauged linear {sigma}-model, which describes a non-compact Calabi-Yau four-fold compactification without branes. This is used in the examples of multi-parameter models to study the various phases of the combined open/closed deformation space. It is furthermore shown how the brane geometry can be related to a F-theory compactification on a compact Calabi-Yau four-fold, where the Hodge-theoretic techniques can be used to compute the G-flux induced Gukov-Vafa-Witten potential. The dual F-theory picture also allows to conjecture the form of the Kaehler potential on the full open/closed deformation space. In the second part we analyze the background dependence of theories which derive from multiple wrapped M5-branes. Using the Kontsevich-Soibelman wall-crossing formula and the theory of mock modular forms we derive a holomorphic

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

    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

  9. Pharmacological therapy for amblyopia

    Anupam Singh

    2017-01-01

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

  10. Pharmacological therapy for amblyopia

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

    2017-01-01

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

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

    Leathard, Helen L.

    2001-01-01

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

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

    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. Breastfeeding information in pharmacology textbooks: a content analysis.

    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.

  14. Reappraisal of GIP Pharmacology for Metabolic Diseases

    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....

  15. [Pharmacological treatment of obesity].

    Gomis Barbará, R

    2004-01-01

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

  16. Pharmacological therapy of spondyloarthritis.

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

    2015-01-01

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

  17. Pharmacology of pediatric resuscitation.

    Ushay, H M; Notterman, D A

    1997-02-01

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

  18. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

    Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

    2002-11-01

    Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their

  19. Pharmacological Aspects of Neuro-Immune Interactions.

    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.

  20. A Multiple Watershed Approach to Assessing the Effects of Habitat Restoration Actions on Anadromous and Resident Fish Populations, Technical Report 2003-2004.

    Marmorek, David

    2004-03-01

    for future habitat restoration actions. Such designs are being developed concurrently with this project by several other groups in the Columbia Basin (RME Workgroup 2003, NMFS 2003, Hillman and Paulsen 2002, Hillman 2003). By addressing questions about habitat restoration and monitoring (in coordination with other related efforts), we hope that this project will catalyze a shift in the Basin's paradigm of habitat restoration, moving from implementation of individual watershed projects towards rigorously designed and monitored, multiwatershed, adaptive management experiments. The project involved three phases of work, which were closely integrated with various related and ongoing efforts in the region: (1) Scoping - We met with a Core Group of habitat experts and managers to scope out a set of testable habitat restoration hypotheses, identify candidate watersheds and recommend participants for a data evaluation workshop. (2) Data Assembly - We contacted over 80 scientists and managers to help evaluate the suitability of each candidate watershed's historical data for assessing the effectiveness of past restoration actions. We eventually settled on the Yakima, Wenatchee, Clearwater, and Salmon subbasins, and began gathering relevant data for these watersheds at a workshop with habitat experts and managers. Data assembly continued for several months after the workshop. (3) Data Analysis and Synthesis - We explored statistical approaches towards retrospectively analyzing the effects of restoration 'treatments' at nested spatial scales across multiple watersheds (Chapters 2-5 of this report). These analyses provided a foundation for identifying existing constraints to testing restoration hypotheses, and opportunities to overcome these constraints through improved experimental designs, monitoring protocols and project selection strategies (Chapters 6 and 7 of this report). Finally, we developed a set of recommendations to improve the design

  1. PHARMACOLOGICAL AND MEDICINAL CHEMISTRY ASPECTS OF CANNABIS COMPOUNDS

    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.

  2. The pharmacology of regenerative medicine.

    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.

  3. Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects.

    Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

    2012-12-01

    Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.

  4. Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

    Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

    2012-09-01

    Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

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

    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.

  6. Pharmacological Overview of Galactogogues

    Felipe Penagos Tabares

    2014-01-01

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

  7. Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

    Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

    2016-07-03

    Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

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

    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. Fuzzy pharmacology: theory and applications.

    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.

  10. Pharmacology of antihistamines

    Martin K Church

    2013-01-01

    Full Text Available H 1- antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H 1 -receptors which are members of the G-protein family. The older first generation H 1- antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H 1 -antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.

  11. The pharmacology of gynaecology.

    Tothill, A

    1980-09-01

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

  12. Precision pharmacology for Alzheimer's disease.

    Hampel, Harald; Vergallo, Andrea; Aguilar, Lisi Flores; Benda, Norbert; Broich, Karl; Cuello, A Claudio; Cummings, Jeffrey; Dubois, Bruno; Federoff, Howard J; Fiandaca, Massimo; Genthon, Remy; Haberkamp, Marion; Karran, Eric; Mapstone, Mark; Perry, George; Schneider, Lon S; Welikovitch, Lindsay A; Woodcock, Janet; Baldacci, Filippo; Lista, Simone

    2018-04-01

    The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses. Consequently, the distinct pattern of AD pathophysiology in space and time must be investigated on the basis of the individual biological makeup. This requires the implementation of systems biology and neurophysiology to facilitate Precision Medicine (PM) and Precision Pharmacology (PP). The regulation of several processes at multiple levels of complexity from gene expression to cellular cycle to tissue repair and system-wide network activation has different time delays (temporal scale) according to the affected systems (spatial scale). The initial failure might originate and occur at every level potentially affecting the whole dynamic interrelated systems within an organism. Unraveling the spatial and temporal dynamics of non-linear pathophysiological mechanisms across the continuum of hierarchical self-organized systems levels and from systems homeostasis to systems failure is key to understand AD. Measuring and, possibly, controlling space- and time-scaled adaptive and compensatory responses occurring during AD will represent a crucial step to achieve the capacity to substantially modify the disease course and progression at the best suitable timepoints, thus counteracting disrupting critical pathophysiological inputs. This approach will provide the conceptual basis for effective

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

    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.

  14. [Pharmacological therapy of obesity].

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

    2008-04-01

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

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

    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.

  16. Nematode cholinergic pharmacology

    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe [ 3 H]N-methylscopolamine ([ 3 H]NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs

  17. Pharmacological treatment of the benign prostatic hyperplasia

    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

  18. Applying linked data approaches to pharmacology: Architectural decisions and implementation

    Gray, A.J.G; Groth, P.T.; Loizou, A.; Askjaer, S; Brenninkmeijer, C; Burger, K.; Chichester, C.; Evelo, C.T.; Goble, C.A.; Harland, L; Pettifier, S; Thompson, M.; Waagmeester, A; William, A.J

    2014-01-01

    The discovery of new medicines requires pharmacologists to interact with a number of information sources ranging from tabular data to scientific papers, and other specialized formats. In this application report, we describe a linked data platform for integrating multiple pharmacology datasets that

  19. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat

    Germain, Dominique P; Hughes, Derralynn A; Nicholls, Kathleen

    2016-01-01

    BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The...

  20. Quality management of pharmacology and safety pharmacology studies

    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...

  1. Current trends and future development in pharmacologic stress testing

    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

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

    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.

  3. Pharmacological features of osthole

    Agata Jarząb

    2017-05-01

    Full Text Available Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities.One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L. Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.. It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects.To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

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

    Ribera, Esteban; Podzamczer, Daniel

    2015-03-01

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

  5. PHARMACOLOGY OF CANNABINOIDS

    Ilonka Ferjan

    2015-06-01

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

  6. Radioimmunoassay in basic and clinical pharmacology

    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

  7. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    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.

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

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

    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.

  10. Pharmacology Experiments on the Computer.

    Keller, Daniel

    1990-01-01

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

  11. Pharmacology of Marihuana (Cannabis sativa)

    Maickel, Roger P.

    1973-01-01

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

  12. Chemotaxonomy and pharmacology of Gentianaceae

    Jensen, Søren Rosendal; Schripsema, Jan

    2002-01-01

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

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

    Xiaoye He

    2011-01-01

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

  14. Factors Affecting the Pharmacology of Antibody–Drug Conjugates

    Andrew T. Lucas

    2018-02-01

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

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

    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

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

    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.

  17. Anthraquinones As Pharmacological Tools and Drugs.

    Malik, Enas M; Müller, Christa E

    2016-07-01

    Anthraquinones (9,10-dioxoanthracenes) constitute an important class of natural and synthetic compounds with a wide range of applications. Besides their utilization as colorants, anthraquinone derivatives have been used since centuries for medical applications, for example, as laxatives and antimicrobial and antiinflammatory agents. Current therapeutic indications include constipation, arthritis, multiple sclerosis, and cancer. Moreover, biologically active anthraquinones derived from Reactive Blue 2 have been utilized as valuable tool compounds for biochemical and pharmacological studies. They may serve as lead structures for the development of future drugs. However, the presence of the quinone moiety in the structure of anthraquinones raises safety concerns, and anthraquinone laxatives have therefore been under critical reassessment. This review article provides an overview of the chemistry, biology, and toxicology of anthraquinones focusing on their application as drugs. © 2016 Wiley Periodicals, Inc.

  18. Targeting HIV latency: pharmacologic strategies toward eradication

    Xing, Sifei; Siliciano, Robert F.

    2013-01-01

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

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

    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.

  20. Naloxone : actions of an antagonist

    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

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

    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.

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

    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.

  3. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

    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.

  4. Pharmacological Treatment for Atrial Fibrillation

    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.

  5. Dynamic reflexivity in action: an armchair walkthrough of a qualitatively driven mixed-method and multiple methods study of mindfulness training in schoolchildren.

    Cheek, Julianne; Lipschitz, David L; Abrams, Elizabeth M; Vago, David R; Nakamura, Yoshio

    2015-06-01

    Dynamic reflexivity is central to enabling flexible and emergent qualitatively driven inductive mixed-method and multiple methods research designs. Yet too often, such reflexivity, and how it is used at various points of a study, is absent when we write our research reports. Instead, reports of mixed-method and multiple methods research focus on what was done rather than how it came to be done. This article seeks to redress this absence of emphasis on the reflexive thinking underpinning the way that mixed- and multiple methods, qualitatively driven research approaches are thought about and subsequently used throughout a project. Using Morse's notion of an armchair walkthrough, we excavate and explore the layers of decisions we made about how, and why, to use qualitatively driven mixed-method and multiple methods research in a study of mindfulness training (MT) in schoolchildren. © The Author(s) 2015.

  6. Pharmacological challenges in chronic pancreatitis

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

    2013-01-01

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

  7. Applications of stable isotopes in clinical pharmacology

    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

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

    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.

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

    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.

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

    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.

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

    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.

  12. Roles of multiple surface sites, long substrate binding clefts, and carbohydrate binding modules in the action of amylolytic enzymes on polysaccharide substrates

    Nielsen, Morten Munch; Seo, E.S.; Dilokpimol, Adiphol

    2008-01-01

    Germinating barley seeds contain multiple forms of alpha-amylase, which are subject to both differential gene expression and differential degradation as part of the repertoire of starch-degrading enzymes. The alpha-amylases are endo-acting and possess a long substrate binding cleft with a charact......Germinating barley seeds contain multiple forms of alpha-amylase, which are subject to both differential gene expression and differential degradation as part of the repertoire of starch-degrading enzymes. The alpha-amylases are endo-acting and possess a long substrate binding cleft...... will address surface sites in both barley alpha-amylase 1 and in the related isozyme 2....

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

    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

  14. Iomazenil: pharmacological and animal data

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

    1990-01-01

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

  15. Pharmacological approach to acute pancreatitis

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  16. Pharmacological approach to acute pancreatitis

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

    2008-01-01

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

  17. Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14 Neurons

    Chin-Wei Huang

    2018-05-01

    Full Text Available Background/Aims: Rotenone (Rot is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

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

    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

  19. Combined action of time-delay and colored cross-associated multiplicative and additive noises on stability and stochastic resonance for a stochastic metapopulation system

    Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong

    2016-05-01

    In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.

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

    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. Pharmacologic therapy for acute pancreatitis

    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

  2. Pharmacological management of panic disorder

    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

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

    Marjan Seyedmazhari

    2013-01-01

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

  4. Pharmacological challenges in chronic pancreatitis

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

    2014-01-01

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

  5. Pharmacological challenges in chronic pancreatitis

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

    2014-01-01

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

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

    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

  7. Pharmacology of human experimental anxiety

    F.G. Graeff

    2003-04-01

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

  8. Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

    Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

    2006-12-15

    The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

  9. Viewpoint Manifolds for Action Recognition

    Souvenir Richard

    2009-01-01

    Full Text Available Abstract Action recognition from video is a problem that has many important applications to human motion analysis. In real-world settings, the viewpoint of the camera cannot always be fixed relative to the subject, so view-invariant action recognition methods are needed. Previous view-invariant methods use multiple cameras in both the training and testing phases of action recognition or require storing many examples of a single action from multiple viewpoints. In this paper, we present a framework for learning a compact representation of primitive actions (e.g., walk, punch, kick, sit that can be used for video obtained from a single camera for simultaneous action recognition and viewpoint estimation. Using our method, which models the low-dimensional structure of these actions relative to viewpoint, we show recognition rates on a publicly available dataset previously only achieved using multiple simultaneous views.

  10. Nutraceutical or Pharmacological Potential of Moringa oleifera Lam.

    Kou, Xianjuan; Li, Biao; Olayanju, Julia B; Drake, Justin M; Chen, Ning

    2018-03-12

    Moringa oleifera Lam. ( M. oleifera ), which belongs to the Moringaceae family, is a perennial deciduous tropical tree, and native to the south of the Himalayan Mountains in northern India. M. oleifera is rich in proteins, vitamin A, minerals, essential amino acids, antioxidants, and flavonoids, as well as isothiocyanates. The extracts from M. oleifera exhibit multiple nutraceutical or pharmacological functions including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neuroprotective, hypoglycemic, and blood lipid-reducing functions. The beneficial functions of M. oleifera are strongly associated with its phytochemicals such as flavonoids or isothiocyanates with bioactivity. In this review, we summarize the research progress related to the bioactivity and pharmacological mechanisms of M. oleifera in the prevention and treatment of a series of chronic diseases-including inflammatory diseases, neuro-dysfunctional diseases, diabetes, and cancers-which will provide a reference for its potential application in the prevention and treatment of chronic diseases or health promotion.

  11. Can Universal SEL Programs Benefit Universally? Effects of the Positive Action Program on Multiple Trajectories of Social-Emotional and Misconduct Behaviors.

    Duncan, Robert; Washburn, Isaac J; Lewis, Kendra M; Bavarian, Niloofar; DuBois, David L; Acock, Alan C; Vuchinich, Samuel; Flay, Brian R

    2017-02-01

    Behavioral trajectories during middle childhood are predictive of consequential outcomes later in life (e.g., substance abuse, violence). Social and emotional learning (SEL) programs are designed to promote trajectories that reflect both growth in positive behaviors and inhibited development of negative behaviors. The current study used growth mixture models to examine effects of the Positive Action (PA) program on behavioral trajectories of social-emotional and character development (SECD) and misconduct using data from a cluster-randomized trial that involved 14 schools and a sample of predominately low-income, urban youth followed from 3rd through 8th grade. For SECD, findings indicated that PA was similarly effective at improving trajectories within latent classes characterized as "high/declining" and "low/stable". Favorable program effects were likewise evident to a comparable degree for misconduct across observed latent classes that reflected "low/rising" and "high/rising" trajectories. These findings suggest that PA and perhaps other school-based universal SEL programs have the potential to yield comparable benefits across subgroups of youth with differing trajectories of positive and negative behaviors, making them promising strategies for achieving the intended goal of school-wide improvements in student outcomes.

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

    Justin C. Moser

    2014-01-01

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

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

    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.

  14. Complex Pharmacology of Free Fatty Acid Receptors

    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...

  15. The Dutch vision of clinical pharmacology

    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

  16. Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

    Locri, Filippo; Amato, Rosario; Marsili, Stefania; Rusciano, Dario; Bagnoli, Paola

    2018-01-01

    Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role. PMID:29517994

  17. Cooperative action of multiple cis-acting elements is required for N-myc expression in branchial arches: specific contribution of GATA3.

    Potvin, Eric; Beuret, Laurent; Cadrin-Girard, Jean-François; Carter, Marcelle; Roy, Sophie; Tremblay, Michel; Charron, Jean

    2010-11-01

    The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb -8.7 to kb +7.2 are sufficient to reproduce the N-myc embryonic expression profile in developing branchial arches and limb buds. These sequences encompass several regulatory elements dispersed throughout the N-myc locus, including an upstream limb bud enhancer, a downstream somite enhancer, a branchial arch enhancer in the second intron, and a negative regulatory element in the first intron. N-myc expression in the limb buds is under the dominant control of the limb bud enhancer. The expression in the branchial arches necessitates the interplay of three regulatory domains. The branchial arch enhancer cooperates with the somite enhancer region to prevent an inhibitory activity contained in the first intron. The characterization of the branchial arch enhancer has revealed a specific role of the transcription factor GATA3 in the regulation of N-myc expression. Together, these data demonstrate that correct N-myc developmental expression is achieved via cooperation of multiple positive and negative regulatory elements.

  18. Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

    Massimo Dal Monte

    2018-03-01

    Full Text Available Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON and is an initial symptom of multiple sclerosis (MS. Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG, were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM, a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®, a balanced mixture of fatty acids (FAs, counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

  19. Cannabidiol inhibits angiogenesis by multiple mechanisms.

    Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

    2012-11-01

    Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

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

    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.

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

    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

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

    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.

  3. Pharmacological Activities of Hypnea musciformis

    Revd Dr Olaleye

    There are reports of antispasmodic a activity of Hypnea musciformis by Salimabi and Das (1980) .... spinal cord and its action in the higher region of the nervous system is believed to help control the mood perhaps even to effect the sleep cycle ...

  4. Pharmacology of sexually compulsive behavior.

    Codispoti, Victoria L

    2008-12-01

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

  5. Future pharmacological therapy in hypertension.

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

    2018-04-26

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

  6. Pharmacological challenges in chronic pancreatitis.

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

    2013-11-14

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

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

    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.

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

    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...

  9. Pharmacological Activity and Clinical Use of PDRN

    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.

  10. Pharmacological Activity and Clinical Use of PDRN

    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

  11. Pharmacological exploration of the resting membrane potential reserve

    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. Differences in pharmacology of tumor necrosis factor (TNF antagonists

    S. Bombardieri

    2011-09-01

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

  13. Approach to pharmacological and clinical applications of Anisi aetheroleum

    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.

  14. Pharmacological treatment of tics in Gilles de la Tourette Syndrome

    Andrea E. Cavanna

    2011-12-01

    Full Text Available Tourette syndrome is a neurodevelopmental disorder characterised by the chronic presence of multiple motor tics (e.g. eye blinking, shoulder shrugging, etc. and at least one vocal/phonic tic (e.g. grunting or sniffing. The clinical picture of patients with Tourette syndrome is often complicated by tic-related behavioural problems and associated psychopathology. The pathophysiology of Tourette syndrome is poorly understood, however converging evidence from neuroimaging studies suggests abnormalities within the fronto-striatal pathways. The pharmacological management of the tic symptoms focuses on the dopaminergic and noradrenergic pathways and aims to improve the health-related quality of life of patients.

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

    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

  16. Problems of pharmacological supply of disaster medicine

    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. [Contribution of animal experimentation to pharmacology].

    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.

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

    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

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

    Katz EG

    2014-08-01

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

  20. Phytochemical and pharmacological overview on Liriopes radix

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

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

    Electronic search engines such as Google, Google scholar, publishing sites such as Elsevier .... A number of pharmacological activities of C. bulbispermum have been ..... bulbispermum using the direct plate method and minimum inhibitory ...

  2. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    Heine, R. ter

    2009-01-01

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

  3. Medicinal, Pharmacological and Phytochemical Potentials of ...

    Medicinal, Pharmacological and Phytochemical Potentials of Annona Comosus linn. ... Therapeutic plants, and the drugs derived from them, are the most important ... also as treatment to: diarrhea, indigestion, pneumonia, bronchitis, arthritis, ...

  4. Disrupting reconsolidation: pharmacological and behavioral manipulations

    Soeter, M.; Kindt, M.

    2011-01-01

    We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited

  5. Pharmaceutical and pharmacological approaches for bioavailability

    2014-01-27

    Jan 27, 2014 ... Etoposide posses high plasma protein binding (97%) and is degraded via ... The present article gives insight on pharmaceutical and pharmacological .... caprolactone and were found efficient as drug delivery vehicles.

  6. ORIGINAL ARTICLES Pharmacological testing in Horner's syndrome

    topical cocaine 10% in both eyes gave an odds ratio of 1 050:1 that. Horner's syndrome ... nerve endings and therefore do not stimulate the effector cells directly. ... Pharmacological testing in Horner's syndrome – a new paradigm. Derrick P ...

  7. Punishment, Pharmacological Treatment, and Early Release

    Ryberg, Jesper

    2013-01-01

    Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....

  8. Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

    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.

  9. Pharmacological interventions for acute pancreatitis.

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

    2017-04-21

    In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin

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

    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

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

    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.

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

    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.

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

    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. Pharmacologic management of neuropathic pain.

    Gordon, Debra B; Love, Georgette

    2004-12-01

    The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

  15. Negotiating action

    2017-12-01

    After years of working towards a climate accord, the Paris Agreement of 2015 marked the shift from negotiating to reach consensus on climate action to implementation of such action. The challenge now is to ensure transparency in the processes and identify the details of what is required.

  16. Enforcement actions: Significant actions resolved

    1994-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  17. Enforcement actions: Significant actions resolved

    1992-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  18. Enforcement actions: Significant actions resolved

    1990-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved

    1989-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Pharmacologic influence on esophageal varices

    Lunderquist, A.; Owman, T.

    1983-01-01

    Selective catherization of the left gastric vein was performed after percutaneous transhepatic portography (PTP) in patients with portal hypertension and esophageal varices. Following the hypothesis that drugs increasing the lower esophageal sphincter (LES) pressure may obstruct the variceal blood flow throught the lower esophagus, the effect of different drugs (i.e., intravenous injection of vasopressin, pentagastrin, domperidone and somatostatin and subcutaneous injection of metacholine) on the variceal blood flow was examined. Vasopressin did not change the variceal blood flow; pentagastrine, with its known effect of increasing the LES pressure produced a total interruption of the flow in four of eight patients; domperiodone, also known to increase the LES pressure obstructed the variceal blood flow in the only patient examined with this drug; somatostatin has no reported action on the LES but blocked the flow in one of two patients; and metacholine, reported to increase the LES pressure did not produce any change in the flow in the three patients examined. LES pressure was recorded before and during vasopressin infusion in seven patients with portal hypertension and esophageal varices. No reaction on the pressure was found. The patient number in the study is small and the results are nonuniform but still they suggest that drugs increasing the LES tonus might be useful to control variceal blood flow. (orig.)

  1. Pharmacological synergy: the next frontier on therapeutic advancement for migraine.

    Blumenfeld, Andrew; Gennings, Chris; Cady, Roger

    2012-04-01

    mechanisms are involved in terminating acute episodes of migraine. Clinicians now capitalize on this observation and use migraine medication in combination with another to improve patient outcomes, for example, using an antiemetic with an opioid or a triptan and NSAIDs. More recently, the Food and Drug Adminstration has approved a combination product containing 85mg of sumatriptan plus 500mg of naproxen sodium for acute treatment of migraine. Clinical trials conducted prior to approval demonstrated that the combination of sumatriptan and naproxen was more effective as a migraine abortive than either of its components but that each component and the combination were more effective than placebo. Exactly how sumatriptan and naproxen interact to create therapeutic synergism is unknown though its mere occurrence suggests that models assisting medical understanding and prediction of pharmacological synergism may improve clinical outcome over products acting through a single receptor mechanism. Migraine is a syndrome, meaning it is defined by observed symptoms rather than known pathophysiology. Multiple pathogenic mechanisms are likely involved in generating this diverse array of symptoms understood as the migraine symptom complex. Sumatriptan and naproxen have independent mechanisms of action and target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine. Sumatriptan acts on the 5-HT(1B) and 5-HT(1D) receptors, whereas naproxen inhibits the COX-1 and COX-2 enzymes. Sumatriptan has vasoconstricting effects as well as effects on neurogenic inflammation by decreasing the release of substance P and calcitonin gene-related peptide. In contrast, naproxen affects prostaglandins and other inflammatory mediators. Because sumatriptan and naproxen both relieve migraine yet interact with different cellular targets within the migraine pathway, it is reasonable to assume there is a unique synergy between these medications that improves treatment

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

    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.

  3. New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?

    Kennett, G A; Clifton, P G

    2010-11-01

    In this review we assess the range of centrally active anorectics that are either in human clinical trials, or are likely to be so in the near future. We describe their weight loss efficacy, mode of action at both pharmacological and behavioural levels, where understood, together with the range of side effects that might be expected in clinical use. We have however evaluated these compounds against the considerably more rigorous criteria that are now being used by the Federal Drugs Agency and European Medicines Agency to decide approvals and market withdrawals. Several trends are evident. Recent advances in the understanding of energy balance control have resulted in the exploitation of a number of new targets, some of which have yielded promising data in clinical trials for weight loss. A second major trend is derived from the hypothesis that improved weight loss efficacy over current therapy is most likely to emerge from treatments targeting multiple mechanisms of energy balance control. This reasoning has led to the development of a number of new treatments for obesity where multiple mechanisms are targeted, either by a single molecule, such as tesofensine, or through drug combinations such as qnexa, contrave, empatic, and pramlintide+metreleptin. Many of these approaches also utilise advances in formulation technology to widen safety margins. Finally, the practicality of peptide therapies for obesity has become better validated in recent studies and this may allow more rapid exploitation of novel targets, rather than awaiting the development of orally available small molecules. We conclude that novel, more efficacious and better tolerated treatments for obesity may become available in the near future. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Pharmacological stress agents in nuclear cardiology

    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)

  5. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    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.

  6. Pharmacological screening technologies for venom peptide discovery.

    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.

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

    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.

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

    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. Perinatal pharmacology: applications for neonatal neurology.

    Smits, Anne; Allegaert, Karel

    2011-11-01

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

  10. Traumatic brain injury pharmacological treatment: recommendations

    Renato Anghinah

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

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

    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

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

    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.

  13. Enforcement actions: Significant actions resolved

    1993-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Enforcement actions: Significant actions resolved

    1991-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  15. Enforcement actions: Significant actions resolved

    1991-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  16. Enforcement actions: Significant actions resolved

    1990-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  17. Enforcement actions: Significant actions resolved

    1990-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  18. Enforcement actions: Significant actions resolved

    1992-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved

    1990-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved

    1993-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  1. Enforcement actions: Significant actions resolved

    1992-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. Enforcement actions: Significant actions resolved

    1993-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  3. Enforcement actions: Significant actions resolved

    1993-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved

    1991-07-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  5. Enforcement actions: Significant actions resolved

    1991-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  6. Enforcement actions: Significant actions resolved

    1992-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  7. Enforcement actions: Significant actions resolved

    1989-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

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

    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

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

    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.

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

    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

  11. Pharmacological therapy of chronic obstructive pulmonary disease

    patients with COPD require pharmacological therapy. ... pulmonary dysfunction. Clearly the patient's tolerance to the various drugs will influence the choice of long-term maintenance treatment. The other important factor in the .... blocking cervical immune responses might leave her less protected against other infections.

  12. Multidimensional Screening as a Pharmacology Laboratory Experience.

    Malone, Marvin H.; And Others

    1979-01-01

    A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

  13. Radioreceptor assay: theory and applications to pharmacology

    Perret, G.; Simon, P.

    1984-01-01

    The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproductibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, β-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising [fr

  14. Ethnomedicinal uses and pharmacological activities of Croton ...

    Abstract. Purpose: To provide an overview of the ethnomedicinal uses and ... calls for detailed phytochemical and pharmacological properties of the species aimed at identifying the ... urban communities throughout its native ... sized, densely leafy tree reaching 15 m tall [17] ..... Williams College, United States; 1998; p 133.

  15. Pharmacological Interventions for Students with ADD.

    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…

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

    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.

  17. Current status and challenges of cytokine pharmacology

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  18. International Journal of Herbs and Pharmacological Research

    International Journal of Herbs and Pharmacological Research (IJHPR) [ISSN: 2315-537X; E- ISSN: 2384-6836] is a peer reviewed journal publication of Anthonio Research Center. The Journal is intended to serve as a medium for the publication of research findings in the field of Herbal medication in developing countries ...

  19. International Journal of Herbs and Pharmacological Research ...

    PROMOTING ACCESS TO AFRICAN RESEARCH ... International Journal of Herbs and Pharmacological Research: Advanced Search ... either term; e.g., education OR research; Use parentheses to create more complex queries; ... African Journal of Biomedical Research, African Journal of Biotechnology, African Journal of ...

  20. Pharmacological management of chronic obstructive pulmonary ...

    The main objective of treatment is to relieve daily symptoms, improve quality of life and importantly decrease the risk of future exacerbations. Current guidelines are based on grade A and B evidence. Pneumococcal and annual influenza vaccinations are encouraged. A holistic approach that augments pharmacological ...

  1. Emerging pharmacological therapy for functional dyspepsia.

    Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

    2013-10-01

    Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

  2. Clinical pharmacology of novel anticancer drug formulations

    Stuurman, F.E.

    2013-01-01

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

  3. Kinship and interaction in neuromuscular pharmacology

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  4. Pharmaceutical and pharmacological approaches for bioavailability

    Much research has been done to determine drug–drug and herb–drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability ...

  5. Chemical constituents, and pharmacological and toxicological ...

    Methods: A large number of research articles related to “Cynomorium songaricum” “pharmacological effects” .... contents in C. songaricum at different stages of its growth are varied in a .... Oral water-soluble polysaccharides of C. ... tested strains, mouse somatic cells and germ cells. .... change under the influence of heating.

  6. Pharmacological Evaluation of the Antidiarrhoeal Activity of ...

    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 ...

  7. Some Pharmacological Aspects of Antimalarial Drugs

    1974-06-15

    Jun 15, 1974 ... Some Pharmacological Aspects of Antimalarial. Drugs. D.BOTHA. SUMMARY. A short review is given of antimalarial drugs currently in use. S. Air. Med. l., 48, 1263 (1974). CLASSIFICATION. The chemotherapy of malaria may be conveniently classi- fied as (i) casual prophylaxis; (ii) suppressive treatment;.

  8. Systems Pharmacology in Small Molecular Drug Discovery

    Wei Zhou

    2016-02-01

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

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

    Purpose: To present an overview of the ethnobotany, phytochemistry and pharmacology of Crinum bulbispermum so as to understand its importance and potential in primary healthcare systems. Methods: A review of the literature was undertaken and an in-depth analysis of previous research on ethnobotany, phytochemistry ...

  10. Plant cannabinoids: a neglected pharmacological treasure trove.

    Mechoulam, Raphael

    2005-12-01

    Most of the cannabinoids in Cannabis sativa L. have not been fully evaluated for their pharmacological activity. A publication in this issue presents evidence that a plant cannabinoid, Delta(9)-tetrahydrocannabivarin is a potent antagonist of anandamide, a major endogenous cannabinoid. It seems possible that many of the non-psychoactive constituents of this plant will be of biological interest.

  11. Molecular Pharmacology of CXCR4 inhibition

    Steen, Anne; Rosenkilde, Mette Marie

    2012-01-01

    pharmacology of well-known CXCR4 antagonists in order to augment the potency and affinity and to increase the specificity of future CXCR4-targeting compounds. In this chapter, binding modes of CXCR4 antagonists that have been shown to mobilize stem cells are discussed. In addition, comparisons between results...

  12. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor

    Wellendorph, Petrine; Goodman, M W; Burstein, E S

    2002-01-01

    The pharmacology of histamine H(3) receptors suggests the presence of distinct receptor isoforms or subtypes. We herein describe multiple, functionally distinct, alternatively spliced isoforms of the human H(3) receptor. Combinatorial splicing at three different sites creates at least six distinct...... receptor isoforms, of which isoforms 1, 2, and 4, encode functional proteins. Detailed pharmacology on isoforms 1 (unspliced receptor), and 2 (which has an 80 amino acid deletion within the third intracellular loop of the protein) revealed that both isoforms displayed robust responses to a series of known...... revealed a rank order of potency at both isoforms of clobenpropit>iodophenpropit>thioperamide, and these drugs are fivefold less potent at isoform 2 than isoform 1. To further explore the pharmacology of H(3) receptor function, we screened 150 clinically relevant neuropsychiatric drugs for H(3) receptor...

  13. Pharmacologic studies in vulnerable populations: Using the pediatric experience.

    Zimmerman, Kanecia; Gonzalez, Daniel; Swamy, Geeta K; Cohen-Wolkowiez, Michael

    2015-11-01

    Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics, innovative clinical trial design, use of quantitative clinical pharmacology methods, pediatric thought leadership, and collaboration have successfully overcome many existing barriers. This success has resulted in improved knowledge on pharmacokinetics, safety, and efficacy of therapeutics in children. To date, research in pregnant women has not been characterized by similar success. Wide gaps in knowledge remain despite the common use of therapeutics in pregnancy. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Action Refinement

    Gorrieri, R.; Rensink, Arend; Bergstra, J.A.; Ponse, A.; Smolka, S.A.

    2001-01-01

    In this chapter, we give a comprehensive overview of the research results in the field of action refinement during the past 12 years. The different approaches that have been followed are outlined in detail and contrasted to each other in a uniform framework. We use two running examples to discuss

  15. Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

    Xuan Ge

    2012-08-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ and peroxisome proliferator-activated receptor alpha (PPARα. A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.

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

    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....

  17. Traditional Chinese Medicine-Based Network Pharmacology Could Lead to New Multicompound Drug Discovery

    Jian Li

    2012-01-01

    Full Text Available Current strategies for drug discovery have reached a bottleneck where the paradigm is generally “one gene, one drug, one disease.” However, using holistic and systemic views, network pharmacology may be the next paradigm in drug discovery. Based on network pharmacology, a combinational drug with two or more compounds could offer beneficial synergistic effects for complex diseases. Interestingly, traditional chinese medicine (TCM has been practicing holistic views for over 3,000 years, and its distinguished feature is using herbal formulas to treat diseases based on the unique pattern classification. Though TCM herbal formulas are acknowledged as a great source for drug discovery, no drug discovery strategies compatible with the multidimensional complexities of TCM herbal formulas have been developed. In this paper, we highlighted some novel paradigms in TCM-based network pharmacology and new drug discovery. A multiple compound drug can be discovered by merging herbal formula-based pharmacological networks with TCM pattern-based disease molecular networks. Herbal formulas would be a source for multiple compound drug candidates, and the TCM pattern in the disease would be an indication for a new drug.

  18. Pharmacists' and general practitioners' pharmacology knowledge and pharmacotherapy skills

    Keijsers, Carolina J P W; Leendertse, Anne J; Faber, Adrianne; Brouwers, Jacobus R B J; de Wildt, Dick J; Jansen, Paul A F

    Understanding differences in the pharmacology knowledge and pharmacotherapy skills of pharmacists and physicians is vital to optimizing interprofessional collaboration and education. This study investigated these differences and the potential influence of work experience. The pharmacology knowledge

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

    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.

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

    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.

  1. Pharmacologic Treatments for Binge-Eating Disorder.

    McElroy, Susan L

    2017-01-01

    Binge-eating disorder (BED) is the most common eating disorder and is associated with poor physical and mental health outcomes. Psychological and behavioral interventions have been a mainstay of treatment for BED, but as understanding of this disorder has grown, pharmacologic agents have become promising treatment options for some patients. At this time, only one drug-the stimulant prodrug lisdexamfetamine-is approved for the treatment of BED. Numerous classes of medications including antidepressants, anticonvulsants, and antiobesity drugs have been explored as off-label treatments for BED with variable success. Although not all patients with BED may be suitable candidates for pharmacotherapy, all patients should be considered for and educated about pharmacologic treatment options. © Copyright 2017 Physicians Postgraduate Press, Inc.

  2. Pharmacology profiling of chemicals and proteins

    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...

  3. Common mullein, pharmacological and chemical aspects

    Muhammad Riaz

    Full Text Available Verbascum thapsus L. [Khardhag or Common mullein], a member of the family Scrophulariaceae, is a famous herb that is found all over Europe, in temperate Asia, in North America and is well-reputed due to its medicinal properties. This medicinal herb contains various chemical constituents like saponins, iridoid and phenylethanoid glycosides, flavonoids, vitamin C and minerals. It is famous in various communities worldwide for the treatment of various disorders of both humans and animals aliments. A number of pharmacological activities such as anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, antihepatotoxic and anti-hyperlipidemic activity have been ascribed to this plant. The plant is used to treat tuberculosis also, earache and bronchitis. In the present paper botanical and ethnomedicinal description, pharmacological profile and phytochemistry of this herb is being discussed.

  4. Pharmacologic management of chronic neuropathic pain

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

    2017-01-01

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

  5. Pharmacological evaluation of bee venom and melittin

    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.

  6. Cellular and Molecular Targets of Menthol Actions

    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. Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16 years from multiple raters in six cohorts in the EU-ACTION project.

    Bartels, Meike; Hendriks, Anne; Mauri, Matteo; Krapohl, Eva; Whipp, Alyce; Bolhuis, Koen; Conde, Lucia Colodro; Luningham, Justin; Fung Ip, Hill; Hagenbeek, Fiona; Roetman, Peter; Gatej, Raluca; Lamers, Audri; Nivard, Michel; van Dongen, Jenny; Lu, Yi; Middeldorp, Christel; van Beijsterveldt, Toos; Vermeiren, Robert; Hankemeijer, Thomas; Kluft, Cees; Medland, Sarah; Lundström, Sebastian; Rose, Richard; Pulkkinen, Lea; Vuoksimaa, Eero; Korhonen, Tellervo; Martin, Nicholas G; Lubke, Gitta; Finkenauer, Catrin; Fanos, Vassilios; Tiemeier, Henning; Lichtenstein, Paul; Plomin, Robert; Kaprio, Jaakko; Boomsma, Dorret I

    2018-05-29

    Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16 years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and

  8. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  9. Local Anesthetics: Review of Pharmacological Considerations

    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

  10. Conception of pharmacological knowledge and needs amongst ...

    Students who are taking/have taken the medical pharmacology course completed an 18-question survey within 10min by marking one/more choices from ... and 31.1% different drugs in a group; 45.8% prefer to study lecturers' notes, 26.7% textbooks, 9.8% the Internet, and 2.7% journals; 46.7% use standard textbooks, ...

  11. Electronic cigarettes and nicotine clinical pharmacology

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

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

  12. Phage Therapy: Eco-Physiological Pharmacology

    Stephen T. Abedon

    2014-01-01

    Full Text Available Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies, impact on body-associated microbiota (as ecological communities, and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

  13. Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations.

    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

  14. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

    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.

  15. Novel kinin B1 receptor agonists with improved pharmacological profiles.

    Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

    2009-04-01

    There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

  16. KIRKIA ACUMINATA OLIV.: A REVIEW OF ITS ETHNOBOTANY AND PHARMACOLOGY.

    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.

  17. Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology

    Yan-Hua Bi

    2018-01-01

    Full Text Available Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both traditional treatment and modern clinical care. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Curcumae Rhizoma using a drug-likeness approach. Candidate protein targets with functions related to cancer were predicted by reverse docking and then checked by manual search of the PubMed database. Potential target genes were uploaded to the GeneMANIA server and DAVID 6.8 database for analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results revealed that the anticancer activity of Curcumae Rhizoma potentially involves 13 active compounds, 33 potential targets, and 31 signaling pathways, thus constituting a “multiple compounds, multiple targets, and multiple pathways” network corresponding to the concept of systematic actions in TCM. These findings provide an overview of the anticancer action of Curcumae Rhizoma from a network perspective, as well as setting an example for future studies of other materials used in TCM.

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

    Agaga, Luther Agbonyegbeni; John, Theresa Adebola

    2016-08-30

    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.

  19. Pharmacological enhancement of treatment for amblyopia

    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

  20. Pharmacological enhancement of treatment for amblyopia

    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

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

    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

  2. Pharmacological consequences of oxidative stress in ocular tissues

    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

  3. Pharmacological consequences of oxidative stress in ocular tissues

    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.

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

    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.

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

    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

  6. Pharmacology Goes Concept-Based: Course Design, Implementation, and Evaluation.

    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.

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

    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.

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

    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 ...

  9. Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics

    ElRakaiby, Marwa; Dutilh, Bas E.; Rizkallah, Mariam R.; Boleij, Annemarie; Cole, Jason N.; Aziz, Ramy K.

    2014-01-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized thera...

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

    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.

  11. Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

    Byrnes, James; Ganetzky, Rebecca; Lightfoot, Richard; Tzeng, Michael; Nakamaru-Ogiso, Eiko; Seiler, Christoph; Falk, Marni J

    2017-07-18

    Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days

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

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

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

  13. Recommendations for the pharmacologic management of allergic rhinitis.

    Hoyte, Flavia C L; Meltzer, Eli O; Ostrom, Nancy K; Nelson, Harold S; Bensch, Greg W; Spangler, Dennis L; Storms, William W; Weinstein, Steven F; Katial, Rohit K

    2014-01-01

    Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.

  14. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris.

    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.

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

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

    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).

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

    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

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

    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.

  19. Action Learning: Avoiding Conflict or Enabling Action

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  20. Pharmacological studies of the lung with PET

    Syrota, A.

    1986-10-01

    Positron emission tomography (PET), known to be used for lung ventilation and perfusion studies, can also be used in pharmacology to obtain information that is otherwise not available. The lung takes up biologically active substances which can be inactivated or activated, and synthesises and releases others. Such information in man has been obtained from samples of human lungs, or from in vivo first-pass studies, invasive or not, as well as from in vivo kinetic studies using external detection methods with scintillation cameras. PET provides now quantitative regional data in the human lung

  1. Chemistry and Pharmacology of Citrus sinensis

    Juan Manuel J. Favela-Hernández

    2016-02-01

    Full Text Available Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs.

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

    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.

  3. Multiple Perspectives / Multiple Readings

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  4. A minimal architecture for joint action

    Vesper, Cordula; Butterfill, Stephen; Knoblich, Günther

    2010-01-01

    What kinds of processes and representations make joint action possible? In this paper we suggest a minimal architecture for joint action that focuses on representations, action monitoring and action prediction processes, as well as ways of simplifying coordination. The architecture spells out...... minimal requirements for an individual agent to engage in a joint action. We discuss existing evidence in support of the architecture as well as open questions that remain to be empirically addressed. In addition, we suggest possible interfaces between the minimal architecture and other approaches...... to joint action. The minimal architecture has implications for theorizing about the emergence of joint action, for human-machine interaction, and for understanding how coordination can be facilitated by exploiting relations between multiple agents’ actions and between actions and the environment....

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

    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.

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

    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.

  7. Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

    Huang, Tao; Zhong, Linda L D; Lin, Chen-Yuan; Zhao, Ling; Ning, Zi-Wan; Hu, Dong-Dong; Zhang, Man; Tian, Ke; Cheng, Chung-Wah; Bian, Zhao-Xiang

    2018-01-01

    Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

  8. The pharmacological management of metabolic syndrome.

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

    2018-04-01

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

  9. Electronic cigarettes and nicotine clinical pharmacology.

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

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

  10. Electronic cigarettes and nicotine clinical pharmacology

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

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

  11. Neuro-pharmacological functional MRI of epilepsy

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji [Okayama Univ. (Japan). School of Medicine; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-03-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

  12. Phytochemical and pharmacological review of Lagenaria sicereria.

    Prajapati, Rakesh P; Kalariya, Manisha; Parmar, Sachin K; Sheth, Navin R

    2010-10-01

    Lagenaria siceraria (Molina) standley (LS) (Family: Cucurbitaceae) is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF), and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated.

  13. Phytochemical and pharmacological review of Lagenaria sicereria

    Rakesh P Prajapati

    2010-01-01

    Full Text Available Lagenaria siceraria (Molina standley (LS (Family: Cucurbitaceae is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF, and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated.

  14. DIVERSE POTENTIAL AND PHARMACOLOGICAL STUDIES OF ARGININE

    Anju Meshram

    2015-09-01

    Full Text Available Arginine is metabolically flexible amino acid with major role in protein synthesis and detoxification of ammonia. It is involved in several metabolic pathways for the production of biologically active compounds such as creatine, nitric oxide, ornithine, glutamate, agmatine, citrulline and polyamines. Regarding this all, we review the crucial role of arginine in metabolism, diversified prospective uses and pharmacological applications. Arginine plays an important role in the treatment of tumorigenesis, asthama, gastric, erectile dysfunction, apoptosis, melanoma and congestive heart failure. Ability to produce nitric oxide offers various applications as in the prevention of age and hair loss. It serves as a precursor of creatine with ergogenic potential. The ability to increase endogenous growth hormone makes arginine a preferred supplement for the improvement of physical performance. In the present study details about the pharmacological applications of arginine based on modern scientific investigations have been discussed. There are immense properties hidden in arginine that need to be explored using the scientific investigations to make it beneficial for the medicine and human health. More research is needed to evaluate the role of arginine supplementation on exercise performance and training adaptations in healthy and diseased populations before taking any conclusions.

  15. Pharmacological treatment of diabetic neuropathic pain.

    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.

  16. Phytochemistry and Pharmacology of Berberis Species

    Mokhber-Dezfuli, Najmeh; Saeidnia, Soodabeh; Gohari, Ahmad Reza; Kurepaz-Mahmoodabadi, Mahdieh

    2014-01-01

    The genus Berberis (Berberidaceae) includes about 500 species worldwide, some of which are widely cultivated in the north-eastern regions of Iran. This genus consists of spiny deciduous evergreen shrubs, characterized by yellow wood and flowers. The cultivation of seedless barberry in South Khorasan goes back to two hundred years ago. Medicinal properties for all parts of these plants have been reported, including: Antimicrobial, antiemetic, antipyretic, antioxidant, anti-inflammatory, anti-arrhythmic, sedative, anti-cholinergic, cholagogic, anti-leishmaniasis, and anti-malaria. The main compounds found in various species of Berberis, are berberine and berbamine. Phytochemical analysis of various species of this genus revealed the presence of alkaloids, tannins, phenolic compounds, sterols and triterpenes. Although there are some review articles on Berberis vulgaris (as the most applied species), there is no review on the phytochemical and pharmacological activities of other well-known species of the genus Berberis. For this reason, the present review mainly focused on the diverse secondary metabolites of various species of this genus and the considerable pharmacological and biological activities together with a concise story of the botany and cultivation. PMID:24600191

  17. Pharmacological modulation of mitochondrial calcium homeostasis.

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  18. Neuro-pharmacological functional MRI of epilepsy

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-01-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

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

    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.

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

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

    2013-01-01

    In a previous analysis of the country of origin of papers published in Naunyn-Schmiedeberg's Archives of Pharmacology, a major shift toward contributions from emerging market countries, was noticed in comparison of 2010 to 2001 publications. Repeating such analysis for 2012 publications in the

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

    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.

  2. Mirror neurons and the action theory of language origins

    Steels, Luc

    2000-01-01

    The research reported here attempts to understand how language may have originated from sensori-motor competences. Recently the observation of mirror neurons has lead to the suggestion that there is not only a rich representation of motor action but also that this representation is used for multiple purposes: action execution, action planning, action imaging, and action recognition. Of particular importance is the observation that one agent can recognise an action plan of another one and t...

  3. Molecular Mechanism for Various Pharmacological Activities of NSAIDS

    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.

  4. Student Engagement in Pharmacology Courses Using Online Learning Tools

    Karaksha, Abdullah; Grant, Gary; Anoopkumar-Dukie, Shailendra; Nirthanan, S. Niru

    2013-01-01

    Objective. To assess factors influencing student engagement with e-tools used as a learning supplement to the standard curriculum in pharmacology courses. Design. 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. Assessment. 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 (pstudent engagement after the implementation of a “marketing strategy” that included e-mail reminders and motivation. PMID:23966728

  5. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae).

    Brinker, Anita M; Ma, Jun; Lipsky, Peter E; Raskin, Ilya

    2007-03-01

    Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

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

    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.

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

    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.

  8. Phytochemical, Toxicological and Pharmacological Studies of ...

    2015-01-23

    Jan 23, 2015 ... activities suggest its therapeutic potentials in drug discovery. Keywords: Asarum ..... box 1 (HMGB1) protein acts as a late mediator of severe vascular ..... and action mechanisms of Sanguisorbae Radix against oxidative stress ...

  9. Pharmacology national board examinations: factors that may influence performance.

    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.

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

    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. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  12. Screening action potentials: The power of light

    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. Clozapine-resistant schizophrenia – non pharmacological augmentation methods

    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.

  14. Quality of reporting statistics in two Indian pharmacology journals

    Jaykaran,; Yadav, Preeti

    2011-01-01

    Objective: To evaluate the reporting of the statistical methods in articles published in two Indian pharmacology journals. Materials and Methods: All original articles published since 2002 were downloaded from the journals′ (Indian Journal of Pharmacology (IJP) and Indian Journal of Physiology and Pharmacology (IJPP)) website. These articles were evaluated on the basis of appropriateness of descriptive statistics and inferential statistics. Descriptive statistics was evaluated on the basis of...

  15. A Review of Pharmacologic Treatment for Compulsive Buying Disorder

    Soares, Célia; Fernandes, Natália; Morgado, Pedro

    2016-01-01

    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 se...

  16. Multiple sclerosis

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  17. [Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

    Liu, Yu-Qian; Zhan, Shu-Yu; Ruan, Yu-Er; Zuo, Zhi-Yan; Ji, Xiao-Ming; Wang, Shuai-Jie; Ding, Bao-Yue

    2017-10-01

    Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae. Copyright© by the Chinese Pharmaceutical Association.

  18. Pharmacological Aspects of Vipera xantina palestinae Venom

    Momic, Tatjana; Arlinghaus, Franziska T.; Arien-Zakay, Hadar; Katzhendler, Jeoshua; Eble, Johannes A.; Marcinkiewicz, Cezary; Lazarovici, Philip

    2011-01-01

    In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation. PMID:22174978

  19. Safety pharmacology--current and emerging concepts.

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas; Sidaway, James; Sison-Young, Rowena; Smith, Emma; Stebbings, Richard; Tingle, Yulia; Valentin, Jean-Pierre; Williams, Awel; Williams, Dominic; Park, Kevin; Goldring, Christopher

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Pharmacological Strategies to Retard Cardiovascular Aging

    Alfaras, Irene; Di Germanio, Clara; Bernier, Michel; Csiszar, Anna; Ungvari, Zoltan; Lakatta, Edward G.; de Cabo, Rafael

    2016-01-01

    Aging is the major risk factor for cardiovascular diseases (CVD), which are the leading cause of death in the United States. Traditionally, the effort to prevent CVD has been focused on addressing the conventional risk factors, including hypertension, hyperglycemia, hypercholesterolemia, and high circulating levels of triglycerides. However, recent preclinical studies have identified new approaches to combat CVD. Calorie restriction has been reproducibly shown to prolong lifespan in various experimental model animals. This has led to the development of calorie restriction mimetics and other pharmacological interventions capable to delay age-related diseases. In this review, we will address the mechanistic effects of aging per se on the cardiovascular system and focus on the pro-longevity benefits of various therapeutic strategies that support cardiovascular health. PMID:27174954

  1. Pharmacologic Implications of Marijuana Use During Pregnancy.

    Fantasia, Heidi Collins

    Marijuana is the most commonly used recreational drug in the United States, including among women of childbearing age and women who are pregnant. Changing legal statutes that allow for the use of medical marijuana and the decriminalization of marijuana for personal use reflect more permissive societal views on the use of this drug. Active compounds in marijuana cross the placenta rapidly and are excreted in breast milk. Results of studies of the effects of marijuana on a developing fetus and neonate are conflicting, but researchers have identified chronic marijuana exposure as a risk factor for preterm birth and small-for-gestational-age infants. This article reviews the pharmacology of marijuana and discusses implications for nurses who work with women of childbearing age. © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  2. Pharmacological Needs of Nurses: Short Communication

    Leila Nazari

    2016-06-01

    Full Text Available Background and objectives : This study was carried out to determine the most commonly used drugs in health centers. By identifying common medications, pharmacological educational needs of nurses gets clear and officials can provide nurses specific relevant training about common drugs. Material and Methods: In this descriptive report, the hospitals’ pharmacies were asked to name ten of the most widely used drugs in the past 6 months. The obtained data were analyzed by SPSS 13 software using descriptive tests. Results: Gastrointestinal drugs and antibiotics in all centers and oxytocin in obstetrics and gynecological centers were the most commonly used drugs. Conclusion: Due to the important and dangerous side-effects of these common medications, renewing nurses’ information in this field is required. ​

  3. Rehabilitation in multiple sclerosis.

    Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

    2017-07-01

    The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

  4. A Quantitative Analysis of Undisclosed Conflicts of Interest in Pharmacology Textbooks.

    Piper, Brian J; Telku, Hassenet M; Lambert, Drew A

    2015-01-01

    Disclosure of potential conflicts of interest (CoI) is a standard practice for many biomedical journals but not for educational materials. The goal of this investigation was to determine whether the authors of pharmacology textbooks have undisclosed financial CoIs and to identify author characteristics associated with CoIs. The presence of potential CoIs was evaluated by submitting author names (N = 403; 36.3% female) to a patent database (Google Scholar) as well as a database that reports on the compensation ($USD) received from 15 pharmaceutical companies (ProPublica's Dollars for Docs). All publications (N = 410) of the ten highest compensated authors from 2009 to 2013 and indexed in Pubmed were also examined for disclosure of additional companies that the authors received research support, consulted, or served on speaker's bureaus. A total of 134 patents had been awarded (Maximum = 18/author) to textbook authors. Relative to DiPiro's Pharmacotherapy: A Pathophysiologic Approach, contributors to Goodman and Gilman's Pharmacological Basis of Therapeutics and Katzung's Basic and Clinical Pharmacology were more frequently patent holders (OR = 6.45, P 1 patent (OR = 0.15, P < .0005). A total of $2,411,080 USD (28.3% for speaking, 27.0% for consulting, and 23.9% for research), was received by 53 authors (Range = $299 to $310,000/author). Highly compensated authors were from multiple fields including oncology, psychiatry, neurology, and urology. The maximum number of additional companies, not currently indexed in the Dollars for Docs database, for which an author had potential CoIs was 73. Financial CoIs are common among the authors of pharmacology and pharmacotherapy textbooks. Full transparency of potential CoIs, particularly patents, should become standard procedure for future editions of educational materials in pharmacology.

  5. Ethnobotany, biochemistry and pharmacology of Minthostachys (Lamiaceae).

    Schmidt-Lebuhn, A N

    2008-08-13

    The South American mint genus Minthostachys is of great importance in the Andes as a medicinal, aromatic, culinary and commercial essential oil plant. After decades of taxonomic confusion and virtual indeterminability of specimens, new systematic and taxonomic work has been conducted in recent years. The present paper attempts to summarize the state of knowledge about Minthostachys with a focus on ethnobotany, analyses of essential oil content and pharmacology, to identify the currently accepted species names for the plants examined in these previous studies, and to assess where additional research is needed. All available studies on Minthostachys were obtained and evaluated. Herbaria were contacted to identify voucher specimens cited in the respective publications. The great majority of published studies was conducted on a single species, Argentinean Minthostachys verticillata. In contrast, the most widely distributed and well-known species (Minthostachys mollis) as well as several locally important and intensively used species (e.g., Minthostachys acutifolia) have received disproportionately little attention, and virtually nothing is known about the local endemics among the 17 species currently recognized. In many cases, however, it is difficult to relate the results to taxonomic entities due to the lack of voucher specimens. Future research efforts should especially be directed at studying the chemistry and potential for use of several common but so far neglected species of the central and northern Andes, at disentangling environmental and genetic influences on essential oil composition, at prerequisites for cultivation, and at the pharmacological basis of the most important traditional uses. Because of the morphological complexity of the genus, future researchers are urged to deposit voucher specimens of the plants used in their studies to facilitate species identification and to make the results more comparable and reproducible.

  6. Clinical pharmacology of atovaquone and proguanil hydrochloride.

    Beerahee, M

    1999-05-01

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

  7. The Safety Pharmacology Society salary survey.

    Pugsley, Michael K; Authier, Simon; Brabham, Tiffini; Soloviev, Maxim; Markgraf, Carrie G; Correll, Krystle; Traebert, Martin; Greiter-Wilke, Andrea; Valentin, Jean-Pierre; Vargas, Hugo; Botchway, Alfred; Leishman, Derek J; Curtis, Michael J

    2017-11-01

    Safety pharmacology is a growing discipline with scientists broadly distributed across international geographical regions. This electronic salary survey is the first to be distributed amongst the entire Safety Pharmacology Society (SPS) membership. An electronic survey was sent to all members of the Society. Categorical survey questions assessed membership employment types, annual incomes, and professional certifications, along with other associated career attributes. This survey was distributed to the SPS membership that is comprised of safety pharmacologists, toxicologists and pharmacologists working globally in the pharmaceutical industry, at contract research organizations (CRO), regulatory agencies, and academia or within the technology provider industry. The survey was open for responses from December 2015 to March 2016. The survey response rate was 28% (129/453). North America (68%) was the region with the largest number of respondents followed by Europe (28%). A preponderance of respondents (77%) had 12years of industry experience or more. 52% of responders earned annually between $40,000 and $120,000. As expected, salary was generally positively correlated with the number of years of experience in the industry or the educational background but there was no correlation between salary and the number of employee's directly supervised. The median salary was higher for male vs female respondents, but so was median age, indicative of no gender 'salary gap'. Our 2016 SPS salary survey results showcased significant diversity regarding factors that can influence salary compensation within this discipline. These data provided insights into the complex global job market trends. They also revealed the level of scientific specialization embedded within the organization, presently uniquely positioned to support the dynamic career paths of current and future safety pharmacologists. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Pharmacological management of obesity in pediatric patients.

    Boland, Cassie L; Harris, John Brock; Harris, Kira B

    2015-02-01

    To review current evidence of pharmacological options for managing pediatric obesity and provide potential areas for future research. A MEDLINE search (1966 to October 2014) was conducted using the following keywords: exenatide, liraglutide, lorcaserin, metformin, obesity, orlistat, pediatric, phentermine, pramlintide, topiramate, weight loss, and zonisamide. Identified articles were evaluated for inclusion, with priority given to randomized controlled trials with orlistat, metformin, glucagon-like peptide-1 agonists, topiramate, and zonisamide in human subjects and articles written in English. References were also reviewed for additional trials. Whereas lifestyle modification is considered first-line therapy for obese pediatric patients, severe obesity may benefit from pharmacotherapy. Orlistat is the only Food and Drug Administration (FDA)-approved medication for pediatric obesity and reduced body mass index (BMI) by 0.5 to 4 kg/m(2), but gastrointestinal (GI) adverse effects may limit use. Metformin has demonstrated BMI reductions of 0.17 to 1.8 kg/m(2), with mild GI adverse effects usually managed with dose titration. Exenatide reduced BMI by 1.1 to 1.7 kg/m(2) and was well-tolerated with mostly transient or mild GI adverse effects. Topiramate and zonisamide reduced weight when used in the treatment of epilepsy. Future studies should examine efficacy and safety of pharmacological agents in addition to lifestyle modifications for pediatric obesity. Lifestyle interventions remain the treatment of choice in pediatric obesity, but concomitant pharmacotherapy may be beneficial in some patients. Orlistat should be considered as second-line therapy for pediatric obesity. Evidence suggests that other diabetes and antiepileptic medications may also provide weight-loss benefits, but safety should be further evaluated. © The Author(s) 2014.

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

    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

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

    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.

  11. MULTIPLE OBJECTS

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

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

    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.

  13. Advances in non-dopaminergic pharmacological treatments of Parkinson's disease

    Sandy eStayte

    2014-05-01

    Full Text Available Since the 1960’s treatments for Parkinson's disease (PD have traditionally been directed to effectively restore or replace dopamine, with L-Dopa the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has created a need to develop new therapies that work in ways other than restoring or replacing dopamine. We provide a comprehensive overview of the emerging non-dopaminergic pharmacological treatments including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors and gene therapy, with a detailed overview of their success in animal models and their translation to human clinical trials. We suggest that further developments in the identification of novel therapeutics, particularly those offering disease-modifying effects, will consistently be met with challenges until improvements in clinical trial design and advances in understanding the basic science of PD are made. We consider how developments in genetics, the possibility that PD may consist of multiple disease states, and potential etiology in non-dopaminergic regions will influence drug development. We conclude that despite the challenges ahead patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable.

  14. Emotional Modulation of Learning and Memory: Pharmacological Implications.

    LaLumiere, Ryan T; McGaugh, James L; McIntyre, Christa K

    2017-07-01

    Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Anatomical and pharmacological characterization of excitatory amino acid receptors

    Monaghan, D.T.

    1985-01-01

    The majority of the excitatory neurotransmission in the vertebrate Central Nervous System is thought to be mediated by acidic amino acid neurotransmitters. However, relatively little is known about the excitatory amino acid receptors and their distribution within the CNS. By analyzing radioligand binding to purified synaptic plasma membranes and to thin tissue sections processed for autoradiography, multiple distinct binding sites were found. These binding sites exhibited the pharmacological properties indicative of the excitatory amino acid receptors, which had been identified by electrophysiological techniques. Specifically, L-[ 3 H]-glutamate and D-[ 3 H]-amino-5-phosphonopentanoate appear to label N-methyl-D-aspartate receptors, L-[ 3 H]-glutamate and [ 3 H]-kainic acid appear to label kainic acid receptors, and L-[ 3 H]-glutamate and [ 3 H]-amino-3-hydroxy-5-methyl-4-isoxazolepropionate appear to label quisqualate receptors. Together, these results confirm the three receptor scheme proposed for excitatory amino acid neurotransmission. These results also show that these transmitter-receptor systems are differentially distributed in the brain, and that the total distribution is consistent with that found by other markers for excitatory amino acid-using neurons

  16. Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology

    Balbani, Aracy Pereira Silveira

    2012-01-01

    Full Text Available Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children.

  17. [New approaches in pharmacology: numerical modelling and simulation].

    Boissel, Jean-Pierre; Cucherat, Michel; Nony, Patrice; Dronne, Marie-Aimée; Kassaï, Behrouz; Chabaud, Sylvie

    2005-01-01

    The complexity of pathophysiological mechanisms is beyond the capabilities of traditional approaches. Many of the decision-making problems in public health, such as initiating mass screening, are complex. Progress in genomics and proteomics, and the resulting extraordinary increase in knowledge with regard to interactions between gene expression, the environment and behaviour, the customisation of risk factors and the need to combine therapies that individually have minimal though well documented efficacy, has led doctors to raise new questions: how to optimise choice and the application of therapeutic strategies at the individual rather than the group level, while taking into account all the available evidence? This is essentially a problem of complexity with dimensions similar to the previous ones: multiple parameters with nonlinear relationships between them, varying time scales that cannot be ignored etc. Numerical modelling and simulation (in silico investigations) have the potential to meet these challenges. Such approaches are considered in drug innovation and development. They require a multidisciplinary approach, and this will involve modification of the way research in pharmacology is conducted.

  18. From gene networks to drugs: systems pharmacology approaches for AUD.

    Ferguson, Laura B; Harris, R Adron; Mayfield, Roy Dayne

    2018-06-01

    The alcohol research field has amassed an impressive number of gene expression datasets spanning key brain areas for addiction, species (humans as well as multiple animal models), and stages in the addiction cycle (binge/intoxication, withdrawal/negative effect, and preoccupation/anticipation). These data have improved our understanding of the molecular adaptations that eventually lead to dysregulation of brain function and the chronic, relapsing disorder of addiction. Identification of new medications to treat alcohol use disorder (AUD) will likely benefit from the integration of genetic, genomic, and behavioral information included in these important datasets. Systems pharmacology considers drug effects as the outcome of the complex network of interactions a drug has rather than a single drug-molecule interaction. Computational strategies based on this principle that integrate gene expression signatures of pharmaceuticals and disease states have shown promise for identifying treatments that ameliorate disease symptoms (called in silico gene mapping or connectivity mapping). In this review, we suggest that gene expression profiling for in silico mapping is critical to improve drug repurposing and discovery for AUD and other psychiatric illnesses. We highlight studies that successfully apply gene mapping computational approaches to identify or repurpose pharmaceutical treatments for psychiatric illnesses. Furthermore, we address important challenges that must be overcome to maximize the potential of these strategies to translate to the clinic and improve healthcare outcomes.

  19. [Pharmacology of the antifungals used in the treatment of aspergillosis].

    Azanza, José Ramón; Sádaba, Belén; Gómez-Guíu, Almudena

    2014-01-01

    The treatment of invasive aspergillosis requires the use of drugs that characteristically have complex pharmacokinetic properties, the knowledge of which is essential to achieve maximum efficacy with minimal risk to the patient. The lipid-based amphotericin B formulations vary significantly in their pharmacokinetic behaviour, with very high plasma concentrations of the liposomal form, probably related to the presence of cholesterol in their structure. Azoles have a variable absorption profile, particularly in the case of itraconazole and posaconazole, with the latter very dependent on multiple factors. This may also lead to variations in voriconazole, which requires considering the possibility of monitoring plasma concentrations. The aim of this article is to review some of the most relevant aspects of the pharmacology of the antifungals used in the prophylaxis and treatment of the Aspergillus infection. For this reason, it includes the most relevant features of some of the azoles normally prescribed in this infection (itraconazole, posaconazole and voriconazole) and the amphotericin B formulations. Copyright © 2014. Published by Elsevier Espana.

  20. Natural products and biological activity of the pharmacologically active cauliflower mushroom Sparassis crispa.

    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.

  1. Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models

    Trame, MN; Lesko, LJ

    2015-01-01

    A systems pharmacology model typically integrates pharmacokinetic, biochemical network, and systems biology concepts into a unifying approach. It typically consists of a large number of parameters and reaction species that are interlinked based upon the underlying (patho)physiology and the mechanism of drug action. The more complex these models are, the greater the challenge of reliably identifying and estimating respective model parameters. Global sensitivity analysis provides an innovative tool that can meet this challenge. CPT Pharmacometrics Syst. Pharmacol. (2015) 4, 69–79; doi:10.1002/psp4.6; published online 25 February 2015 PMID:27548289

  2. Natural Products and Biological Activity of the Pharmacologically Active Cauliflower Mushroom Sparassis crispa

    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.

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

    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.

  4. An Integrated Approach to Instruction in Pharmacology and Therapeutics

    Talbert, Robert L.; Walton, Charles A.

    1976-01-01

    The impact of the clinical faculty on the content of the pharmacology course is described in a discussion of trends in pharmacology instruction. Interfaculty communication and development of course objectives are reviewed, and descriptions of two baccalaureate courses at the University of Texas College of Pharmacy are appended. (LBH)

  5. Human pharmacology of current and new treatments for schizophrenia

    Liem-Moolenaar, Marieke

    2012-01-01

    The studies in this thesis together show different ways of studying human pharmacology, give an impression of the current drug development in schizophrenia, and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers. The investigated

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

    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....

  7. Non-pharmacological modulation of cerebral white matter organization

    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...

  8. Pharmacological intervention with oxidative burst in human neutrophils

    Nosál, R.; Drábiková, K.; Jančinová, V.; Mačičková, T.; Pečivová, J.; Perečko, T.; Harmatha, Juraj

    2017-01-01

    Roč. 10, č. 2 (2017), s. 56-60 ISSN 1337-6853 Institutional support: RVO:61388963 Keywords : human neutrophils * oxidative burst * tharapeutical drugs * natural antioxidants Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy https://www.degruyter.com/downloadpdf/j/intox.2017.10.issue-2/intox-2017-0009/intox-2017-0009.pdf

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

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

    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.

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

    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.

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

    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).

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

    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.

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

    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

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

    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.

  16. Traditional uses, phytochemistry and pharmacology of the medicinal species of the genus Cordia (Boraginaceae).

    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.

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

    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.

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

    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.

  19. Pharmacological interventions for antisocial personality disorder.

    Khalifa, Najat; Duggan, Conor; Stoffers, Jutta; Huband, Nick; Völlm, Birgit A; Ferriter, Michael; Lieb, Klaus

    2010-08-04

    Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties. To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September 2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009). Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately. Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data. Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The

  20. [Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research].

    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.

  1. Ghrelin and Ghrelin Receptor Modulation of Psychostimulant Action

    Paul Jeff Wellman

    2013-09-01

    Full Text Available Ghrelin (GHR is an orexigenic gut peptide that modulates multiple homeostatic functions including gastric emptying, anxiety, stress, memory, feeding and reinforcement. GHR is known to bind and activate growth-hormone secretagogue receptors (termed GHR-Rs. Of interest to our laboratory has been the assessment of the impact of GHR modulation of the locomotor activation and reward/reinforcement properties of psychostimulants such as cocaine and nicotine. Systemic GHR infusions augment cocaine stimulated locomotion and conditioned place preference (CPP in rats, as does food restriction which elevates plasma ghrelin levels. Ghrelin enhancement of psychostimulant function may occur owing to a direct action on mesolimbic dopamine function or may reflect an indirect action of ghrelin on glucocorticoid pathways. Genomic or pharmacological ablation of GHR-Rs attenuates the acute locomotor-enhancing effects of nicotine, cocaine, amphetamine and alcohol and blunts the CPP induced by food, alcohol, amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like amphetamine and cocaine, repeated administration of nicotine induces locomotor sensitization in rats. Inactivation of ghrelin circuit function in rats by injection of a ghrelin receptor antagonist (e.g. JMV 2959 diminishes the development of nicotine-induced locomotor sensitization. These results suggest a key permissive role for GHR-R activity for the induction of locomotor sensitization to nicotine. Our finding that GHR-R null rats exhibit diminished patterns of responding for intracranial self-stimulation complements an emerging literature implicating central GHR circuits in drug reward/reinforcement. Finally, antagonism of GHR-Rs may represent a smoking cessation modality that not only blocks nicotine-induced reward but that also may limit weight gain after smoking cessation.

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

    Craighead, Linda W.; Agras, W. Stewart

    1991-01-01

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

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

    Zhao WE

    2016-04-01

    Full Text Available Wen-en Zhao,1 Guoqing Shi,2 Huihui Gu,1,3 Nguyen Ba Ngoc1,4 1School of Chemical Engineering and Energy, Zhengzhou University, 2School of Food and Bioengineering, Zhengzhou University of Light Industry, 3School of Life Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Faculty of Food Industry, College of Food Industry, Da Nang, Vietnam Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ has been shown to play an important role in the biological effects of carotenoids. The PPARγ-signaling pathway is involved in the anticancer effects of carotenoids. Activation of PPARγ partly contributes to the growth-inhibitory effects of carotenoids (β-carotene, astaxanthin, bixin, capsanthin, lutein, and lycopene on breast cancer MCF7 cells, leukemia K562 cells, prostate cancer (LNCaP, DU145, and PC3 cells, and esophageal squamous cancer EC109 cells. PPARγ is the master regulator of adipocyte differentiation and adipogenesis. Downregulated PPARγ and PPARγ-target genes have been associated with the suppressive effects of β-carotene and lycopene on 3T3L1 and C3H10T1/2 adipocyte differentiation and adipogenesis. ß-Carotene is cleaved centrally into retinaldehyde by BCO1, the encoding gene being a PPARγ-target gene. Retinaldehyde can be oxidized to retinoic acid and also be reduced to retinol. β-Carotene can also be cleaved asymmetrically into β-apocarotenals and β-apocarotenones by BCO2. The inhibitory effects of β-carotene on the development of adiposity and lipid storage are dependent substantially on BCO1-mediated production of retinoids. The effects of β-carotene on body adiposity were absent in BCO1-knockout mice. Retinoid metabolism is connected with the activity of PPARγ in the control of body-fat reserves. Retinoic acid, retinaldehyde, retinol, and β-apocarotenals exert suppressive effects on preadipocyte differentiation and adipogenesis via downregulation of PPARγ expression in cell culture. The molecular mechanisms underlying retinoic acid effects on adipose-tissue biology and the development of adiposity remain poorly understood. Adiposity can be affected by retinoids through long-lasting effects at critical developmental stages. Retinol saturase increases PPARγ-transcriptional activity and adipocyte differentiation. Other carotenoids that have been reported to suppress adipocyte differentiation and lipid accumulation in the main via modulation of PPARγ and PPARγ-target genes include astaxanthin, bixin, norbixin, β-cryptoxanthin, fucoxanthin and its metabolites, lycopene, apo-10’-lycopenoic acid, siphonaxanthin, and neoxanthin, except paprika pigments. Lutein, lycopene, and paprika carotenoids reduce proinflammatory cytokine levels by an induction of PPARγ in immune tissues and cells. Lycopene, apo-10’-lycopenoic acid, and astaxanthin might prevent atherosclerosis through modifying cholesterol metabolism via increasing PPARγ expression in macrophages. Keywords: carotenoids, PPARγ, anti-cancer, anti-obesity, antiatherosclerosis

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

    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. DAPs: Deep Action Proposals for Action Understanding

    Escorcia, Victor; Caba Heilbron, Fabian; Niebles, Juan Carlos; Ghanem, Bernard

    2016-01-01

    action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates

  6. Pharmacological Treatment Of Body Dysmorphic Disorder.

    Hong, Kevin; Nezgovorova, Vera; Uzunova, Genoveva; Schlussel, Danya; Hollander, Eric

    2018-04-26

    Body dysmorphic disorder is a challenging disorder that manifests as erroneously perceived flaws in one's physical appearance and repetitive behaviors in response to appearance concerns. This disorder is also frequently comorbid with other psychiatric disorders, including major depressive disorder and autism spectrum disorder. It is currently understood to arise from a combination of biological, psychological, and environmental factors. Treatment of body dysmorphic disorder typically consists of a combination of pharmacotherapy and cognitive behavioral therapy. However, not all patients respond to treatment, and BDD symptoms remain even in those who do respond. This review outlines current pharmacological and neuromodulation treatments for body dysmorphic disorder, and suggests directions for future studies of novel treatments such as augmentation with atypical antipsychotics and the use of intranasal oxytocin in cases of body dysmorphic disorder that show residual symptomatology even with tailored monotherapy. There is emerging evidence suggesting that non-invasive neurostimulatory techniques, such as repetitive transcranial magnetic stimulation, may be of value in treatment-resistant cases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Tinnitus: Network pathophysiology-network pharmacology

    Ana Belen eElgoyhen

    2012-01-01

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

  8. Tinnitus: network pathophysiology-network pharmacology.

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

    2012-01-01

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

  9. Non-pharmacological intervention for memory decline

    Maria eCotelli

    2012-03-01

    Full Text Available Non-pharmacological treatment of memory difficulties in healthy older adults, as well as those with brain damage and neurodegenerative disorders, has gained much attention in recent years (Ball et al., 2002, Willis et al., 2006, Acevedo and Loewenstein, 2007. The two main reasons that explain this growing interest in memory rehabilitation are the limited efficacy of current drug therapies and the plasticity of the human central nervous system (Cotelli et al., 2011c and the discovery that during aging, the connections in the brain are not fixed but retain the capacity to change with learning.Moreover, several studies have reported enhanced cognitive performance in patients with neurological disease, following non-invasive brain stimulation (i.e., repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS to specific cortical areas. The present review provides an overview of memory rehabilitation in individuals with Mild Cognitive Impairment (MCI and in patients with Alzheimer’s Disease (AD with particular regard to cognitive rehabilitation interventions focused on memory and non-invasive brain stimulation. Reviewed data suggest that in patients with memory deficits, memory intervention therapy could lead to performance improvements in memory, nevertheless further studies need to be conducted in order to establish the real value of this approach.

  10. Pharmacological treatment of cardiac glycoside poisoning.

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

    2016-03-01

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

  11. Caffeine use in sports. A pharmacological review.

    Sinclair, C J; Geiger, J D

    2000-03-01

    Caffeine is the most widely ingested psychoactive drug in the world. As many know, chronic use of caffeine leads to dependence, tolerance, drug craving, and upon abrupt cessation unpleasant withdrawal symptoms. Thus, caffeine fulfills pharmacological criteria by which agents are classified as drugs of abuse. Nevertheless, its use is legal and only at high, but readily attainable, levels is it banned from sport. Its use is widespread by athletes as young as 11 years of age who are seeking athletic advantage over fellow competitors. It is likely that its use will not decline any time soon because it is inexpensive, readily available, medically quite safe, socially acceptable, and by most measures legal. However, at levels allowed in sport, caffeine through its wide-ranging physiological and psychological effects increases endurance in well-trained athletes. If the goal of drug-testing and education programs in sport is to protect the health of athletes, prevent unfair advantage (cheating) and encourage ethical behavior then it seems obvious that the allowable levels of caffeine ingestion should be decreased. The alternative is to continue with policies designed largely to punish only those that get caught.

  12. Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

    Domínguez-Clavé, Elisabet; Soler, Joaquim; Elices, Matilde; Pascual, Juan C; Álvarez, Enrique; de la Fuente Revenga, Mario; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

    2016-09-01

    Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT 2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one's own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Safety pharmacology — Current and emerging concepts

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

    2013-01-01

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

  14. Safety pharmacology — Current and emerging concepts

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others

    2013-12-01

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

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

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

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

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

    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.

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

    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.

  18. Multiple sclerosis

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

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

    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

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

    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

  1. Givental action and trivialisation of circle action

    Dotsenko, V.; Shadrin, S.; Vallette, B.

    2015-01-01

    In this paper, we show that the Givental group action on genus zero cohomological field theories, also known as formal Frobenius manifolds or hypercommutative algebras, naturally arises in the deformation theory of Batalin-Vilkovisky algebras. We prove that the Givental action is equal to an action

  2. Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

    Hadjiconstantinou, Maria; Neff, Norton H

    2011-06-01

    Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

  3. Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology.

    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.

  4. Hibiscus sabdariffa L., roselle calyx, from ethnobotany to pharmacology

    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

  5. Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents.

    Lucas, Stephanie; Soave, Claire; Nabil, Ghazal; Ahmed, Zainab Sabry Othman; Chen, Guohua; El-Banna, Hossny Awad; Dou, Q Ping; Wang, Jian

    2017-01-01

    Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics through inhibition of cancer metabolism. Nicotinamide Adenine Dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer. The main objective of this article is to review the recent patents which develop and implicate the chemical inhibitors of the key NAD+ biosynthetic enzymes for cancer treatment. We first discuss the biological principles of NAD+ metabolism in normal and malignant cells, with a focus on the feasibility of selectively targeting cancer cells by pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT) and indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), the rate-limiting salvage and de novo NAD+ biosynthetic enzymes, respectively. We then analyze a series of recent patents on development and optimization of chemical scaffolds for inhibiting NAMPT or IDO/TDO enzymes as potential anticancer drugs. Conclusion and Results: We have reviewed 16 relevant patents published since 2015, and summarized the chemical properties, mechanisms of action and proposed applications of the patented compounds. Without a better understanding of the properties of these compounds, their utility for further optimization and clinical use is unknown. For the compounds that have been tested using cell and mouse models of cancer, results look promising and clinical trials are currently ongoing to see if these results translate to improved cancer treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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

    2011-04-01

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

  7. Syndecans as modulators and potential pharmacological targets in cancer progression

    Despoina eBarbouri

    2014-02-01

    Full Text Available Extracellular matrix (ECM components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs, a family of transmembrane heparan sulfate proteoglycans (HSPGs. Specifically, heparan sulfate (HS chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs, ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma.

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

    Elizabeth Fitelson

    2010-12-01

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

  9. Clinical pharmacology in Russia-historical development and current state.

    Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

    2015-02-01

    Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

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

    Levy, Jerrold H

    2005-09-15

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

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

    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)

  12. 2-Aminothiophene scaffolds: Diverse biological and pharmacological attributes in medicinal chemistry.

    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.

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

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

    2013-07-30

    chemical constituent or multiple ingredients contributes its pharmacological effects. Additionally, chemicals and their pharmacological effects of the other parts such as the aerial part of this plant should be exploited in order to avoid resource waste and find new chemical constituents. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Impulsive action and motivation.

    Frijda, Nico H

    2010-07-01

    This paper explores the way in which emotions are causal determinants of action. It argues that emotional events, as appraised by the individual, elicit changes in motive states (called states of action readiness), which in turn may (or may not) cause action. Actions can be elicited automatically, without prior intention (called impulsive actions), or intentionally. Impulsive actions reflect the simplest and biologically most general form in which emotions can cause action, since they require no reflection, no foresight, and no planning. Impulsive actions are determined conjointly by the nature of action readiness, the affordances perceived in the eliciting event as appraised, and the individual's action repertoire. Those actions from one's repertoire are performed that both match the perceived affordances and the aim of the state of action readiness. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Pharmacological screening of Ageratum conyzoides L. (mentrasto

    Lucia A. Yamamoto

    1991-01-01

    Full Text Available The pharmacological activities of a water extract (WE of Ageratum conyzoides L, a plant populary known for its analgesic and anti-inflamatory properties, were studied in vivo and in vitro preparations. Oral administration (p.o. of the water extract (WE, 0.1 to 5 g/Kg to rats and mice induced quietness and reduced the spontaneous motility. the sleeping time induced by sodium pentobarbital (50 mg/Kg, i.p. in mice was not altered by previous treatment with We (2 g/Kg, p.o.. The same treatment did not influence the paw edema induced by carrageenan or dextran, nor did it reduce the chronic paw edema induced by complete Freund's adjuvant or formaldehyde in rats. The tail flick response in immersion test and writhings induced by 0.8%acetic acid in mice were not altered by WE either. In isolated guinea-pig ilea WE (0.4 to 4 mg/ml did not alter the EC50 values of histamine or acetylcholine, but reduced the maximal response to the agonists by 20 to 50%. We (0.01 to 10 mg/ml produced tonic contractions of the ileal smooth muscle proportional to the doses, reaching a maximum of 75% relatively to the maximum obtained with histamine. Those contractions were blocked by diphenhydramine (10 nM and reduced by 32% in presence of atropine (10 nM. The results indicated that oral treatment of rodents with A. conyzoides L neither reduced the inflammatory edema nor did it decrease the reaction to pain stimuli. In vitro the extract presented an unexpected histamine-like activity characteristic of a partial agonist. The results did not confirm the popular medicinal indications of the plant.

  16. Brain connectivity in pathological and pharmacological coma

    Quentin Noirhomme

    2010-12-01

    Full Text Available Recent studies in patients with disorders of consciousness (DOC tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low level cortical activation in response to external stimulation in patients in a vegetative state or unresponsive wakefulness syndrome. While activation of these primary sensory cortices does not necessarily reflect conscious awareness, activation in higher order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread fronto-parietal global neuronal workspace in DOC patients including the midline default mode network, ‘intrinsic’ system, and the lateral frontoparietal cortices or ‘extrinsic system’. Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between intrinsic and extrinsic brain networks.

  17. Multiple homicides.

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  18. How research in behavioral pharmacology informs behavioral science.

    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.

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

    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.

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

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

    2017-08-01

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