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
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
Directory of Open Access Journals (Sweden)
Shoude Zhang
2014-01-01
Full Text Available During the past decades, a number of studies have demonstrated multiple beneficial health effects of green tea. Polyphenolics are the most biologically active components of green tea. Many targets can be targeted or affected by polyphenolics. In this study, we excavated all of the targets of green tea polyphenolics (GTPs though literature mining and target calculation and analyzed the multiple pharmacology actions of green tea comprehensively through a network pharmacology approach. In the end, a total of 200 Homo sapiens targets were identified for fifteen GTPs. These targets were classified into six groups according to their related disease, which included cancer, diabetes, neurodegenerative disease, cardiovascular disease, muscular disease, and inflammation. Moreover, these targets mapped into 143 KEGG pathways, 26 of which were more enriched, as determined though pathway enrichment analysis and target-pathway network analysis. Among the identified pathways, 20 pathways were selected for analyzing the mechanisms of green tea in these diseases. Overall, this study systematically illustrated the mechanisms of the pleiotropic activity of green tea by analyzing the corresponding “drug-target-pathway-disease” interaction network.
Multiple sclerosis: general features and pharmacologic approach
International Nuclear Information System (INIS)
Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio
2009-01-01
Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)
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.
Proteomic Contributions to Medicinal Plant Research: From Plant Metabolism to Pharmacological Action
Directory of Open Access Journals (Sweden)
Akiko Hashiguchi
2017-12-01
Full Text Available Herbal medicine is a clinical practice of utilizing medicinal plant derivatives for therapeutic purposes. It has an enduring history worldwide and plays a significant role in the fight against various diseases. Herbal drug combinations often exhibit synergistic therapeutic action compared with single-constituent dosage, and can also enhance the cytotoxicity induced by chemotherapeutic drugs. To explore the mechanism underlying the pharmacological action of herbs, proteomic approaches have been applied to the physiology of medicinal plants and its effects on animals. This review article focuses on the existing proteomics-based medicinal plant research and discusses the following topics: (i plant metabolic pathways that synthesize an array of bioactive compounds; (ii pharmacological action of plants tested using in vivo and in vitro studies; and (iii the application of proteomic approaches to indigenous plants with scarce sequence information. The accumulation of proteomic information in a biological or medicinal context may help in formulating the effective use of medicinal plants.
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.
Energy Technology Data Exchange (ETDEWEB)
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)
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.
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.
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.
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.
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
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.
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.
[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.
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.
Pharmacological management of spasticity in multiple sclerosis
DEFF Research Database (Denmark)
Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo
2016-01-01
Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods...... improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity...... and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence...
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
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.
Directory of Open Access Journals (Sweden)
Zhong-Rong Zhang
2015-01-01
Full Text Available This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl-2H-1-benzopyran-2-one, a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP and cyclic adenosine monophosphate (cGMP level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine.
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
Cardiovascular Pharmacology of Sinomenine: The Mechanical and Electropharmacological Actions
Directory of Open Access Journals (Sweden)
Seiichiro Nishida
2007-01-01
Full Text Available Sinomenine is one of the alkaloids extracted from Chinese medical plant, Sinomenium acutum Rehder et Wilson. Sinomenine has been used for Rheumatoid arthritis as an anti-inflammatory and immunomodulative drugs. We have so far been investigated the cardiovascular pharmacological actions of sinomenine. Sinomenine dilated NE (5 μM-, KCl (60 mM- and PDB (300 nM-induced vasoconstrictions. The pretreatment with nicardipine (0.1 μM, staurosporine (30 nM, L-NMMA (100 μM, indomethacin (10 μM or propranolol significantly attenuated the sinomenine-induced vasorelaxation. Therefore, these results indicate that sinomenine causes the vasorelaxation by the involvement with the inhibitions of Ca 2+ current (I Ca and PK-C, β-adrenoceptor stimulation, and the activation of NO and PGI 2 syntheses in endothelium. On the other hand, in the ventricular cardiomyocytes of guinea pig, sinomenine inhibits I Ca and simultaneously decreases the delayed rectifier K + current (I K , resulting in the prolongation of action potential duration. Sinomenine also suppresses the dysrhysmias induced by triggered activities under the Ca 2+ overload condition. Therefore, sinomenine may be expected as one of effective therapeutic drugs for heart failure and dysrhythmias, and may maintain the cardiovascular functions due to modulation of cardiac ionic channels and blood vessels.
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.
National Research Council Canada - National Science Library
Evers, Alex S; Maze, M; Kharasch, Evan D
2011-01-01
...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...
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
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.
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.
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.
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.
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.
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.
d-Lysergic Acid Diethylamide (LSD as a Model of Psychosis: Mechanism of Action and Pharmacology
Directory of Open Access Journals (Sweden)
Danilo De Gregorio
2016-11-01
Full Text Available d-Lysergic Acid Diethylamide (LSD is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1 and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA mechanism or acting on TAAR1 receptors.
Pharmacological study on traditional Chinese medicine and natural product in China
Institute of Scientific and Technical Information of China (English)
Yong-xiang ZHANG
2017-01-01
China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to
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.
Developmental paediatric anaesthetic pharmacology
DEFF Research Database (Denmark)
Hansen, Tom Giedsing
2015-01-01
Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...
Directory of Open Access Journals (Sweden)
Ali Asghar Arastoo
2013-04-01
Full Text Available Objectives: To compare the effectiveness of two treatment methods of ‘combination pharmacological treatment and treadmill training’ and ‘pharmacological treatment’ on management of multiple sclerosis (MS female patients. Methods: In this quasi experimental and interventional study a sample of 20 MS patients (mean age: 36.75 years with Expanded Disability Status Scale scores (EDSS 1.0 to 4.0 were randomly assigned to a ‘pharmacologic treatment’ (Ph group and a combination group of ‘pharmacologic treatment& treadmill training’ (PhTT. All these individuals used the drugs of choice ‘Rebif’ and ‘Avonex’. The intervention consisted of 8-weeks (24 sessions of treadmill training (30 minutes each, at 40-75% of age-predicted maximum heart rate for the PhTT group. The Ph group followed their own routine treatment program. Balance, speed and endurance of walking, quality of life and fatigue were measured by Berg Balance Score, 10 meter timed walk test, 2 minute walk test, and Fatigue Severity Scale (FFS. Data were analyzed by paired t test and one way ANOVA. Results: Comparison of results indicated that pre and post intervention led to significant improvements in the balance score (P=0.001, 10m walk time (P=0.001, walking endurance (P=0.007, and FFS (P=0.04 in the PhTT group. In contrast, no significant changes were observed in the Ph group’s balance score, 10m timed walk and fatigue, while there was a significant decrease in the 2min walking distance (P=0.015 in this group. Discussion: These results suggest that treadmill training in combination with pharmacological treatment improve balance and walking capacity and level of fatigue in women with mild to moderate MS.
[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.
[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.
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
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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.
Pharmacological effects of two cytolysins isolated from the sea ...
Indian Academy of Sciences (India)
Sticholysins I and II (St I/II) are cytolysins purified from the sea anemone Stichodactyla helianthus. In this study, we show their pharmacological action on guinea-pig and snail models in native and pH-denatured conditions in order to correlate the pharmacological findings with the pore-forming activity of both isoforms.
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.
Where and how to manage: Optimal selection of conservation actions for multiple species.
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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.
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).
CLINICAL PHARMACOLOGY OF DIURETICS
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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.
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
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.
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
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.
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…
A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia
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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.
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
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.
Beyond reverse pharmacology: Mechanism-based screening of Ayurvedic drugs
Directory of Open Access Journals (Sweden)
R D Lele
2010-01-01
Full Text Available This paper reviews the pharmacology of Indian medicinal plants, starting with the historical background of European work on the subject beginning as early as the 17th century, and tracing its history through the work of Sen and Bose in the 1930′s, and Vakhil′s historic 1949 paper on Sarpaghanda. The often crucial role of patient feedback in early discoveries is highlighted, as is the time lag between proof of pharmacological action and identification of the active principle, and subsequent elucidation of mechanism of action. In the case of Indian plants in the 20th century this process sometimes took almost 50 years. Reserpine and its mechanisms are given in detail, and its current relevance to public health discussed. The foundation of present day methods of pharmacology is briefly presented so the complexity of methods used to identify properties of Ayurveda derived drugs like forskolin and baicalein, and their bioavailability, may be better appreciated. Ayurveda derived anti-oxidants and their levels of action, immuno-modulators, particularly with respect to the NF-kB pathway and its implications for cancer control, are all considered. The example of curcumin derived from turmeric is explained in more detail, because of its role in cancer prevention. Finally, the paper emphasizes the importance of Ayurveda′s concepts of rasayana as a form of dietary chemo-prevention; the significance of ahar, diet, in Ayurveda′s aspiration to prevent disease and restore health thus becomes clear. Understood in this light, Ayurveda may transcend pharmacology as a treatment paradigm.
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
Directory of Open Access Journals (Sweden)
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.
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.
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.
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.
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.
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).
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
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
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
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.
PHARMACOLOGICAL AND MEDICINAL CHEMISTRY ASPECTS OF CANNABIS COMPOUNDS
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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.
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
International Nuclear Information System (INIS)
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
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.
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.
Pharmacological Profile of Quinoxalinone
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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.
Trials of Pharmacological Interventions for Tourette Syndrome: A Systematic Review
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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.
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
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.
Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity
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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.
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.
Pharmacology and function of melatonin receptors
International Nuclear Information System (INIS)
Dubocovich, M.L.
1988-01-01
The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-[125I]iodomelatonin are identical. It is proposed that 2-[125I]iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-[125I]iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references
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Hui Wang
2014-01-01
Full Text Available Rhizoma Coptidis (Huang Lian in Chinese pinyin is among the most widely used traditional Chinese herbal medicines and has a profound history of more than 2000 years of being used as a therapeutic herb. The antidiabetic effects of Rhizoma Coptidis have been extensively investigated in animal experiments and clinical trials and its efficacy as a promising antihyperglycemic agent has been widely discussed. In the meantime, findings from modern pharmacological studies have contributed the majority of its bioactivities to berberine, the isoquinoline alkaloids component of the herb, and a number of experiments testing the antidiabetic effects of berberine have been initiated. Therefore, we conducted a review of the current evidence profile of the antihyperglycemic effects of Rhizoma Coptidis as well as its main component berberine and the possible mechanism of actions, in order to summarize research evidence in this area and identify future research directions.
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).
Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH
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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.
[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.
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.
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)
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.
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.
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.
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
Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat
DEFF Research Database (Denmark)
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...
Factors Affecting the Pharmacology of Antibody–Drug Conjugates
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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.
Current trends and future development in pharmacologic stress testing
International Nuclear Information System (INIS)
Bae, Jin Ho; Lee, Jae Tae
2005-01-01
Pharmacologic stress testing for myocardial perfusion imaging is a widely used noninvasive method for the evaluation of known or suspected coronary artery disease. The use of exercise for cardiac stress has been practiced for over 60 years and clinicians are familiar with its using. However, there are inevitable situations in which exercise stress is inappropriate. A large number of patients with cardiac problems are unable to exercise to their full potential due to comorbidity such as osteoarthritis, vascular disease and pulmonary disease and a standard exercise stress test for myocardial perfusion imaging is suboptimal means for assessment of coronary artery disease. This problem has led to the development of the pharmacologic stress test and to a great increase in its popularity. All of the currently used pharmacologic agents have well-documented diagnostic value. This review deals the physiological actions, clinical protocols, safety, nuclear imaging applications of currently available stress agents and future development of new vasodilating agents
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.
Low prevalence of hypertension with pharmacological treatments and associated factors
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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.
Pharmacological treatment of the benign prostatic hyperplasia
International Nuclear Information System (INIS)
Perez Guerra, Yohani; Molina Cuevas, Vivian; Oyarzabal Yera, Ambar; Mas Ferreiro, Rosa
2011-01-01
Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5α-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the aα 1 -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5aα-reductase inhibitors, the aα 1 -adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an aα 1 -adrenoceptor antagonist, aα 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product
Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency
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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
Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer
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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.
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
α-Mangostin from Garcinia mangostana Linn: An updated review of its pharmacological properties
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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.
Gaultheria: Phytochemical and Pharmacological Characteristics
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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.
Directory of Open Access Journals (Sweden)
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.
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.
Pharmacological ascorbate and ionizing radiation (IR increase labile iron in pancreatic cancer
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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.
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.
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.
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.
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.
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
Pharmacological Studies of p, N-(3, 4-Methylenedioxy phenyl Benzoic Acid (RRL-1364 - Part-I
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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.
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.
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
Reappraisal of GIP Pharmacology for Metabolic Diseases
DEFF Research Database (Denmark)
Finan, Brian; Müller, Timo D; Clemmensen, Christoffer
2016-01-01
Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....
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.
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.
Screening action potentials: The power of light
Directory of Open Access Journals (Sweden)
Lars eKaestner
2011-07-01
Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.
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
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.
Pharmacologic perspectives of functional selectivity by the angiotensin II type 1 receptor
DEFF Research Database (Denmark)
Aplin, Mark; Christensen, Gitte Lund; Hansen, Jakob Lerche
2008-01-01
and to sudden injury occurring in the circulatory system. Hence, current drugs that block all AT(1) receptor actions most likely leave room for improvement. Recent developments show that two major signaling pathways used by the AT(1) receptor may be dissected by pharmacologic means. Key pathologic responses...... protein actions and simultaneous activation of G protein-dependent or -independent signaling could therefore be desirable in certain situations. The previously unappreciated concept of "functional selectivity" makes this exact strategy feasible and may yield improved drugs for cardiovascular therapy....
Treatment of post-partum depression: a review of clinical, psychological and pharmacological options
Directory of Open Access Journals (Sweden)
Elizabeth Fitelson
2010-12-01
Full Text Available Elizabeth Fitelson1, Sarah Kim4, Allison Scott Baker3, Kristin Leight21Director, 2Attending Psychiatrist, TheWomen's Program, 3Child and Adolescent Psychiatry Fellow, Division of Child Psychiatry, 4PGY-I Resident in Psychiatry, Department of Psychiatry, Columbia University Medical Center, New York, NY, USAAbstract: Postpartum depression (PPD is a common complication of childbearing, and has increasingly been identified as a major public health problem. Untreated maternal depression has multiple potential negative effects on maternal-infant attachment and child development. Screening for depression in the perinatal period is feasible in multiple primary care or obstetric settings, and can help identify depressed mothers earlier. However, there are multiple barriers to appropriate treatment, including concerns about medication effects in breastfeeding infants. This article reviews the literature and recommendations for the treatment of postpartum depression, with a focus on the range of pharmacological, psychotherapeutic, and other non-pharmacologic interventions. Keywords: postpartum depression, postnatal depression, lactation, antidepressant, hormone therapy, psychotherapy, bright light therapy, omega-3
Directory of Open Access Journals (Sweden)
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.
Quality management of pharmacology and safety pharmacology studies
DEFF Research Database (Denmark)
Spindler, Per; Seiler, Jürg P
2002-01-01
to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...
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.
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.
Pharmacological exploration of the resting membrane potential reserve
DEFF Research Database (Denmark)
van der Heyden, Marcel A G; Jespersen, Thomas
2016-01-01
as well as by exchangers and pumps. This review will focus on the relative and regulated contribution of IK1, IK,ACh and IK,Ca, and on pharmacological modification of the channels underlying these currents in respect to the resting membrane potential, Na(+) channel availability and atrial......The cardiac action potential arises and spreads throughout the myocardium as a consequence of highly organized spatial and temporal expression of ion channels conducting Na(+), Ca(2+) or K(+) currents. The cardiac Na(+) current is responsible for the initiation and progression of the action...... potential. Altered Na(+) current has been found implicated in a number of different arrhythmias, including atrial fibrillation. In the atrium, the resting membrane potential is more depolarized than in the ventricles, and as cardiac Na(+) channels undergo voltage-dependent inactivation close...
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.
Endothelial actions of atrial and B-type natriuretic peptides.
Kuhn, Michaela
2012-05-01
The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the
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
Delirium in the elderly: A systematic review of pharmacological and non-pharmacological treatments
Directory of Open Access Journals (Sweden)
Cecília Carboni Tardelli Cerveira
Full Text Available ABSTRACT Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood. OBJECTIVE: To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium. METHODS: This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed, EMBASE, Cochrane CENTRAL and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate. CONCLUSION: Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.
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.
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.
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.
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.
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.
Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions
Directory of Open Access Journals (Sweden)
Seung-Yeol eNah
2015-10-01
Full Text Available Ginseng, the root of Panax ginseng, is used as a traditional medicine. Despite the long history of the use of ginseng, there is no specific scientific or clinical rationale for ginseng pharmacology besides its application as a general tonic. The ambiguous description of ginseng pharmacology might be due to the absence of a predominant active ingredient that represents ginseng pharmacology. Recent studies show that ginseng abundantly contains lysophosphatidic acids (LPAs, which are phospholipid-derived growth factor with diverse biological functions including those claimed to be exhibited by ginseng. LPAs in ginseng form a complex with ginseng proteins, which can bind and deliver LPA to its cognate receptors with a high affinity. As a first messenger, gintonin produces second messenger Ca2+ via G protein-coupled LPA receptors. Ca2+ is an intracellular mediator of gintonin and initiates a cascade of amplifications for further intercellular communications by activation of Ca2+-dependent kinases, receptors, gliotransmitter and neurotransmitter release. Ginsenosides, which have been regarded as primary ingredients of ginseng, cannot elicit intracellular [Ca2+]i transients, since they lack specific cell surface receptor. However, ginsenosides exhibit non-specific ion channel and receptor regulations. This is the key characteristic that distinguishes gintonin from ginsenosides. Although the current discourse on ginseng pharmacology is focused on ginsenosides, gintonin can definitely provide a mode of action for ginseng pharmacology that ginsenosides cannot. This review article introduces a novel concept of ginseng ligand-LPA receptor interaction and proposes to establish a paradigm that shifts the focus from ginsenosides to gintonin as a major ingredient representing ginseng pharmacology.
Approach to pharmacological and clinical applications of Anisi aetheroleum
Directory of Open Access Journals (Sweden)
Khaled Mohamed Mohamed Koriem
2015-01-01
Full Text Available Anisi aetheroleum is the oil obtained from Pimpinella anisum L. (P. anisum by steam distillation. P. anisum seeds were air-dried, and then the dry seeds were crushed, pulverized, and weighed in sequence for anise oil preparation. P. anisum is one of the oldest medicinal plants that belong to family Apiaceae. The fruit of P. anisum is harvested in August and September. P. anisum is widespread in Asia, Africa and Europe. Local names of P. anisum include anise, anisoon, roomy, saunf, sweet cumin and yansoon. The anise oil odour is aromatic while the oil tastes sweet. The average daily dose of Anisi aetheroleum is 0.3 g. trans-Anethole is the major ingredient of the anise oil. Anisi aetheroleum also displays a protective action against neurotoxicity. In addition, Anisi aetheroleum increases glucose absorption and reduces urine output in the rat. The plant oil have pharmacological (antimicrobial, hepatoprotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects and clinical effects on nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields, it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.
DEFF Research Database (Denmark)
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...
Cellular and Molecular Targets of Menthol Actions
Directory of Open Access Journals (Sweden)
Murat Oz
2017-07-01
Full Text Available Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions of menthol. There has been new evidence demonstrating that menthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at least some of the biological and pharmacological effects of menthol can be mediated by alterations in cellular excitability. In this article, we examine the results of earlier studies on the actions of menthol with voltage and ligand-gated ion channels.
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.
International Nuclear Information System (INIS)
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
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.
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.
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
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.
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
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.
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
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.
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.
A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae
Directory of Open Access Journals (Sweden)
Panthati Murali Krishna
2012-10-01
Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.
A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae
Directory of Open Access Journals (Sweden)
Panthati Murali Krishna
2012-04-01
Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.
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.
Viewpoint Manifolds for Action Recognition
Directory of Open Access Journals (Sweden)
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.
Effects of various pharmacological agents on exposed heart of uromastix hardwickii
International Nuclear Information System (INIS)
Qureshi, M.A.; Mahmood, A.
2011-01-01
Background: The pharmacological and physiological studies on cardiac activity of reptiles specifically of Uromastix hardwickii are scarcely available in literature, as well as the effects of parasympathetic and sympathetic agonists together are also not available. Therefore, the mechanical and electrophysiological effects of pharmacological agents, like Physostigmine and its effects before and after Adrenaline administration were observed on the exposed and intact heart of a reptile, Uromastix hardwickii. Method: To work on exposed heart of Uromastix hardwickii, Physostigmine and Adrenaline were prepared by dissolving 0.01 gm in 10 ml of distilled water. Oscillograph was used to record the mechanical and electrical activity of intact heart through isotonic transducer. Result: Physostigmine was found to produce significant effect on Systolic Force (SF), Duration of cardiac cycle (DCC) and Duration of Phase 4 (DP4). Significant effect of Physostigmine was also observed on heart rate (HR) before Adrenaline administration and on DP4 after Adrenaline administration. Conclusion: It was confirmed that Physostigmine does not exhibit its normal effect on Amplitude of Action Potential, cardiac cycle (CC), Duration of action potential (DAP), Plateau Duration and DP4. Physostigmine is affecting the cardiac activity of this reptile without inhibiting the cholinesterase and not accumulating the Acetylcholine. It modulates the effects of Adrenaline when used before the administration of Adrenaline. (author)
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...
Clinical Pharmacology and Pharmacokinetics of Levetiracetam
Directory of Open Access Journals (Sweden)
Chanin Clark Wright
2013-12-01
Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.
Goel, R K; Gawande, D Y; Lagunin, A A; Poroikov, V V
2018-01-01
Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.
PhLeGrA: Graph Analytics in Pharmacology over the Web of Life Sciences Linked Open Data.
Kamdar, Maulik R; Musen, Mark A
2017-04-01
Integrated approaches for pharmacology are required for the mechanism-based predictions of adverse drug reactions that manifest due to concomitant intake of multiple drugs. These approaches require the integration and analysis of biomedical data and knowledge from multiple, heterogeneous sources with varying schemas, entity notations, and formats. To tackle these integrative challenges, the Semantic Web community has published and linked several datasets in the Life Sciences Linked Open Data (LSLOD) cloud using established W3C standards. We present the PhLeGrA platform for Linked Graph Analytics in Pharmacology in this paper. Through query federation, we integrate four sources from the LSLOD cloud and extract a drug-reaction network, composed of distinct entities. We represent this graph as a hidden conditional random field (HCRF), a discriminative latent variable model that is used for structured output predictions. We calculate the underlying probability distributions in the drug-reaction HCRF using the datasets from the U.S. Food and Drug Administration's Adverse Event Reporting System. We predict the occurrence of 146 adverse reactions due to multiple drug intake with an AUROC statistic greater than 0.75. The PhLeGrA platform can be extended to incorporate other sources published using Semantic Web technologies, as well as to discover other types of pharmacological associations.
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.
Metabolic actions of FGF21: molecular mechanisms and therapeutic implications
Directory of Open Access Journals (Sweden)
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.
Directory of Open Access Journals (Sweden)
Katz EG
2014-08-01
Full Text Available Eric G Katz,1 Ronny BW Tan,2 Daniel Rittenberg,1 Wayne J Hellstrom3 1Tulane University School of Medicine, New Orleans, LA, USA; 2Department of Urology, Tan Tock Seng Hospital, Singapore; 3Section of Andrology, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA Abstract: The treatment modalities of erectile dysfunction range from oral pharmacotherapy to intracavernosal injections, intraurethral pellets, vacuum erectile devices, and the surgical option of penile prosthesis insertion. Oral phosphodiesterase 5 inhibitors still remain the preferred treatment for patients since they are the least invasive, not to mention that they can be prescribed by non-urologists. Due to these factors, there has been development of newer drugs with fewer side effects. This is a review of the second generation phosphodiesterase 5 inhibitor, avanafil, looking into its pharmacology as well as its clinical utility. Avanafil's faster onset and shorter duration of action has made it preferred as compared to other PDE5 inhibitors for patients with multiple comorbidities. Keywords: phosphodiesterase 5 inhibitors, impotence, sildenafil, sexual dysfunction, nitric oxide
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.
New concepts in antimalarial use and mode of action in dermatology.
Kalia, Sunil; Dutz, Jan P
2007-01-01
Although chloroquine, hydroxychloroquine and quinacrine were originally developed for the treatment of malaria, these medications have been used to treat skin disease for over 50 years. Recent clinical data have confirmed the usefulness of these medications for the treatment of lupus erythematosus. Current research has further enhanced our understanding of the pharmacologic mechanisms of action of these drugs involving inhibition of endosomal toll-like receptor (TLR) signaling limiting B cell and dendritic cell activation. With this understanding, the use of these medications in dermatology is broadening. This article highlights the different antimalarials used within dermatology through their pharmacologic properties and mechanism of action, as well as indicating their clinical uses. In addition, contraindications, adverse effects, and possible drug interactions of antimalarials are reviewed.
Faraone, Stephen V
2018-04-01
Psychostimulants, including amphetamines and methylphenidate, are first-line pharmacotherapies for individuals with attention-deficit/hyperactivity disorder (ADHD). This review aims to educate physicians regarding differences in pharmacology and mechanisms of action between amphetamine and methylphenidate, thus enhancing physician understanding of psychostimulants and their use in managing individuals with ADHD who may have comorbid psychiatric conditions. A systematic literature review of PubMed was conducted in April 2017, focusing on cellular- and brain system-level effects of amphetamine and methylphenidate. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2. There is also evidence for interactions with glutamate and opioid systems. Clinical implications of these actions in individuals with ADHD with comorbid depression, anxiety, substance use disorder, and sleep disturbances are discussed. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.
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
International Nuclear Information System (INIS)
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
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.
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.
International Nuclear Information System (INIS)
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
Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis
Directory of Open Access Journals (Sweden)
di Nuzzo L
2014-05-01
Full Text Available Luigi di Nuzzo,1 Rosamaria Orlando,2 Carla Nasca,1 Ferdinando Nicoletti1,31Department of Physiology and Pharmacology, Sapienza University of Rome, 2IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, 3IRCCS Neuromed, Pozzilli, ItalyAbstract: New oral drugs have considerably enriched the therapeutic armamentarium for the treatment of multiple sclerosis. This review focuses on the molecular pharmacodynamics of fingolimod, dimethyl fumarate (BG-12, laquinimod, and teriflunomide. We specifically comment on the action of these drugs at three levels: 1 the regulation of the immune system; 2 the permeability of the blood–brain barrier; and 3 the central nervous system. Fingolimod phosphate (the active metabolite of fingolimod has a unique mechanism of action and represents the first ligand of G-protein-coupled receptors (sphingosine-1-phosphate receptors active in the treatment of multiple sclerosis. Dimethyl fumarate activates the nuclear factor (erythroid-derived 2-related factor 2 pathway of cell defense as a result of an initial depletion of reduced glutathione. We discuss how this mechanism lies on the border between cell protection and toxicity. Laquinimod has multiple (but less defined mechanisms of action, which make the drug slightly more effective on disability progression than on annualized relapse rate in clinical studies. Teriflunomide acts as a specific inhibitor of the de novo pyrimidine biosynthesis. We also discuss new unexpected mechanisms of these drugs, such as the induction of brain-derived neurotrophic factor by fingolimod and the possibility that laquinimod and teriflunomide regulate the kynurenine pathway of tryptophan metabolism.Keywords: demyelinating diseases, pharmacotherapy, fingolimod, dimethyl fumarate, laquinimod, teriflunomide
Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond
Directory of Open Access Journals (Sweden)
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.
A fast Na+/Ca2+-based action potential in a marine diatom.
Directory of Open Access Journals (Sweden)
Alison R Taylor
Full Text Available BACKGROUND: Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and
Directory of Open Access Journals (Sweden)
Yingxue Fu
2014-10-01
Full Text Available Identified as a treasure of natural herbal products, traditional Chinese medicine (TCM has attracted extensive attention for their moderate treatment effect and lower side effect. Cardio-cerebrovascular diseases (CCVD are a leading cause of death. TCM is used in China to prevent and treat CCVD. However, the complexity of TCM poses challenges in understanding the mechanisms of herbs at a systems-level, thus hampering the modernization and globalization of TCM. A novel model, termed traditional Chinese medicine systems pharmacology (TCMSP analysis platform, which relies on the theory of systems pharmacology and integrates absorption, distribution, metabolism, excretion and toxicity (ADME/T evaluation, target prediction and network/pathway analysis, was proposed to address these problems. Here, we review the development of systems pharmacology, the TCMSP approach and its applications in the investigations of CCVD and compare it with other methods. TCMSP assists in uncovering the mechanisms of action of herbal formulas used in treating CCVD. It can also be applied in ascertaining the different syndrome patterns of coronary artery disease, decoding the multi-scale mechanisms of herbs, and in understanding the mechanisms of herbal synergism.
Biochemical and pharmacological characterization of irradiated crotamine by gamma rays of 60Co
International Nuclear Information System (INIS)
Oliveira, Karina Corleto
2014-01-01
The serum production in Brazil, the only effective treatment in cases of snakebites, uses horses that although large size, have reduced l lifespan compared with horses not immunized. Ionizing radiation has been shown as an excellent tool in reducing the toxicity of venoms and toxins isolated, and promote the achievement of better immunogens for serum production, and contributing to the welfare of serum-producing animals. It is known, however, that the effects of ionizing radiation on protein are characterized by various chemical modifications, such as fragmentation, cross-linking due to aggregation and oxidation products generated by water radiolysis. However, the action of gamma radiation on toxins is not yet fully understood structurally and pharmacologically, a fact that prevents the application of this methodology in the serum production process. So we proposed in this paper the characterization of crotamine, an important protein from the venom of Crotalus durissus terrificus species, irradiated with 60 Co gamma rays. After isolating the toxin by chromatographic techniques and testing to prove the obtaining of pure crotamine, it was irradiated with gamma rays and subjected to structural analysis, Fluorescence and Circular Dichroism. Using high hydrostatic pressure tests were also conducted in order to verify that the conformational changes caused by radiation suffer modifications under high pressures. From the pharmacological point of view, muscle contraction tests were conducted with the objective of limiting the action of crotamine in smooth muscle as well as the change in the action of toxin caused structural changes to the front. Analysis of Circular Dichroism and Fluorescence showed changes in structural conformation of crotamine when subjected to gamma radiation and that such changes possibly occurring in the secondary and tertiary structure of the protein. The observed in pharmacological tests showed that the irradiated crotamine was less effective in
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.
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.
Imaging tools to study pharmacology: functional MRI on small rodents
Directory of Open Access Journals (Sweden)
Elisabeth eJonckers
2015-10-01
Full Text Available Functional Magnetic Resonance Imaging (fMRI is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD fMRI techniques, including resting state (rsfMRI, stimulus-evoked (st-fMRI, and pharmacological MRI (phMRI. Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anaesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically-induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest (ROIs. In addition, fMRI techniques allow one to dissect how specific modifications (e.g. treatment, lesion etc. modulate the functioning of specific brain areas (st-fMRI, phMRI and how functional connectivity (rsfMRI between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with
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.
Verapamil for cluster headache. Clinical pharmacology and possible mode of action
DEFF Research Database (Denmark)
Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob
2009-01-01
is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...
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.
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.
Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V
2015-05-01
Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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
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.
DEFF Research Database (Denmark)
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...
Energy Technology Data Exchange (ETDEWEB)
Chargari, C. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Service d' oncologie radiotherapie, hopital d' instruction des armees du Val-de-Grace, 74, boulevard de Port-Royal, 75230 Paris cedex 5 (France); Leteur, C.; Ferte, C.; Deberne, M.; Lahon, B.; Rivera, C. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Bourhis, J.; Deutsch, E. [Upres EA 27-10, laboratoire de radiobiologie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, universite Paris-Sud 11, 114, rue edouard-Vaillant, 94805 Villejuif (France)
2011-07-15
The central role of p53 after exposure to ionizing radiation has been widely demonstrated. Mdm2, the main cellular regulator of p53, is a promising target for radiosensitizing purposes. In this article, we review the most recent data on the pharmacological targeting of Mdm2, with focus on strategies of radiosensitization. Antitumor activity of Mdm2 inhibitors has been related with activation of p53-dependant apoptosis, action on DNA repair systems, and anti-angiogenic activity. Preliminary data suggested a synergic interaction between Mdm2 inhibitors and ionizing radiations. However, no clinical data has been published yet on the pharmacological targeting of Mdm2. Given their new mechanisms of action, these new molecules should be subject to careful clinical assessment. Although promising, these strategies expose to unexpected toxicities. (authors)
The relationship between impulsive choice and impulsive action: a cross-species translational study.
Directory of Open Access Journals (Sweden)
Nienke Broos
Full Text Available Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task and impulsive action (five-choice serial reaction time task paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT and impulsive action (immediate and delayed memory task, IMT/DMT. Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action and filled out the Barratt impulsiveness scale (BIS-11. Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1 self-reported impulsivity (BIS-11; (2 impulsive action (IMT/DMT and SST; (3 impulsive choice (DDT. This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.
[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.
Differences in pharmacology of tumor necrosis factor (TNF antagonists
Directory of Open Access Journals (Sweden)
S. Bombardieri
2011-09-01
Full Text Available The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.. The differences in their molecular structure, mechanism of action, pharmacokinetics (PK and pharmacodynamics (PD are discussed, along with the differences concerning dose, administration regimens, drug concentrations and pharmacological interactions. In order to explain the clinical differences observed when these agents are used in the “real world”, which can arise from the respective PK characteristics (kinetics, route and frequency of administration, type of TNF binding, effects on cytokines and PD responses and peculiar mechanisms of action, with distinctive immune function (LFTa inactivation; apoptosis induction, TNF immunoprecipitation, C1q binding and CDC induction; Fcg cross-linking and ADCC induction, the dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.
Energy Technology Data Exchange (ETDEWEB)
Hassan, S H.M. [Durng Research Dept., National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)
1995-10-01
The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab.
International Nuclear Information System (INIS)
Hassan, S.H.M.
1995-01-01
The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab
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
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.
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.
DEFF Research Database (Denmark)
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...
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.
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
International Nuclear Information System (INIS)
Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio; Khalil, Omar Arafat Kdudsi; Carvalho, Claudio Teodoro de; Bannach, Gilbert
2011-01-01
Free radicals are highly reactive species generated in living organisms for the purpose of protection. However, in some circumstances, they are responsible for the occurrence or aggravation of tissue damage. Many anti-inflammatory drugs have a direct effect on free radicals and not radical reactive species, which contributes to its actions against inflammation. Ketoprofen is a nonsteroidal anti-inflammatory agent that generates free radicals by photo irradiation and has an important hemolytic effect with that. The complexation of metals to different drugs has been used as a strategy to improve the pharmacological action of different molecules and reduce their side effects. This paper presents the results of ketoprofen and their metallic complexes action on erythrocytes and free radicals. It was observed that the cerium enhances the scavenger properties of ketoprofen on free radicals, while copper enhances its action over non-radical oxidants. Copper also reduced the hemolytic effect presented by ketoprofen meanwhile its cerium derivative maintained it. (author)
A database of whole-body action videos for the study of action, emotion, and untrustworthiness.
Keefe, Bruce D; Villing, Matthias; Racey, Chris; Strong, Samantha L; Wincenciak, Joanna; Barraclough, Nick E
2014-12-01
We present a database of high-definition (HD) videos for the study of traits inferred from whole-body actions. Twenty-nine actors (19 female) were filmed performing different actions-walking, picking up a box, putting down a box, jumping, sitting down, and standing and acting-while conveying different traits, including four emotions (anger, fear, happiness, sadness), untrustworthiness, and neutral, where no specific trait was conveyed. For the actions conveying the four emotions and untrustworthiness, the actions were filmed multiple times, with the actor conveying the traits with different levels of intensity. In total, we made 2,783 action videos (in both two-dimensional and three-dimensional format), each lasting 7 s with a frame rate of 50 fps. All videos were filmed in a green-screen studio in order to isolate the action information from all contextual detail and to provide a flexible stimulus set for future use. In order to validate the traits conveyed by each action, we asked participants to rate each of the actions corresponding to the trait that the actor portrayed in the two-dimensional videos. To provide a useful database of stimuli of multiple actions conveying multiple traits, each video name contains information on the gender of the actor, the action executed, the trait conveyed, and the rating of its perceived intensity. All videos can be downloaded free at the following address: http://www-users.york.ac.uk/~neb506/databases.html. We discuss potential uses for the database in the analysis of the perception of whole-body actions.
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.
Convergence and divergence, a concept for explaining drug actions.
Watanabe, Takehiko; Kamisaki, Yoshinori; Timmerman, Henk
2004-10-01
For the teaching and/or learning about drug actions and for the discovery and development of new drugs, it is important to understand how drugs act on living bodies. So far, there has been no clear description on the general principle of drug action in pharmacology textbooks. We propose two principles to depict the action mechanism of drugs. The first is that most, if not all, drugs act on proteins at the molecular level, that is, enzymes, receptors, ion channels, and transporters. The second is that a drug may cause divergent or convergent responses, resulting in changes of a physiological or pathological function of the human body. The concept of divergence and convergence can be used to explain the complex individuality of drug actions.
Directory of Open Access Journals (Sweden)
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.
Bianchi, Matt T; Botzolakis, Emmanuel J
2010-03-02
The traditional emphasis on developing high specificity pharmaceuticals ("magic bullets") for the treatment of Neurological and Psychiatric disorders is being challenged by emerging pathophysiology concepts that view disease states as abnormal interactions within complex networks of molecular and cellular components. So-called network pharmacology focuses on modifying the behavior of entire systems rather than individual components, a therapeutic strategy that would ideally employ single pharmacological agents capable of interacting with multiple targets ("magic shotguns"). For this approach to be successful, however, a framework for understanding pharmacological "promiscuity"--the ability of individual agents to modulate multiple molecular targets--is needed. Pharmacological promiscuity is more often the rule than the exception for drugs that target the central nervous system (CNS). We hypothesize that promiscuity is an important contributor to clinical efficacy. Modulation patterns of existing therapeutic agents may provide critical templates for future drug discovery in Neurology and Psychiatry. To demonstrate the extent of pharmacological promiscuity and develop a framework for guiding drug screening, we reviewed the ability of 170 therapeutic agents and endogenous molecules to directly modulate neurotransmitter receptors, a class of historically attractive therapeutic targets in Neurology and Psychiatry. The results are summarized in the form of 1) receptor-centric maps that illustrate the degree of promiscuity for GABA-, glycine-, serotonin-, and acetylcholine-gated ion channels, and 2) drug-centric maps that illustrated how characterization of promiscuity can guide drug development. Developing promiscuity maps of approved neuro-pharmaceuticals will provide therapeutic class-based templates against which candidate compounds can be screened. Importantly, compounds previously rejected in traditional screens due to poor specificity could be reconsidered in this
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
Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology
Directory of Open Access Journals (Sweden)
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.
Directory of Open Access Journals (Sweden)
Caroline Addison Carvalho Xavier
2008-01-01
Full Text Available CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável.BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985
Radioimmunoassay in basic and clinical pharmacology
International Nuclear Information System (INIS)
Patrono, C.; Peskar, B.A.
1987-01-01
The subject of the book is the development, validation and application of radioimmunoassay (RIA) techniques for the measurement of a variety of substances in animal and human body fluids. The book discusses methodological and conceptual issues related to the main classes of mediators of drug action and to drugs themselves, as assayed by this particular analytical technique. A number of introductory chapters provide basic information concerning production and characterization of antibodies, labeling techniques, statistical aspects and validation criteria, insight into problems related to the development and validation of RIA for the newly discovered mediator(s). In the following chapters, the emphasis is placed on the technical details relevant to each class of compounds and on specific aspects of their applications to basic and/or clinical pharmacological studies. New developments in this area, such as monoclonal antibodies and non-radioactive labeling techniques, are also covered
Amino acid neurotransmitters and new approaches to anticonvulsant drug action.
Meldrum, B
1984-01-01
Amino acids provide the most universal and important inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate, cysteic acid, cysteine sulphinic acid) neurotransmitters in the brain. An anticonvulsant action may be produced (1) by enhancing inhibitory (GABAergic) processes, and (2) by diminishing excitatory transmission. Possible pharmacological mechanisms for enhancing GABA-mediated inhibition include (1) GABA agonist action, (2) GABA prodrugs, (3) drugs facilitating GABA release from terminals, (4) inhibition of GABA-transaminase, (5) allosteric enhancement of the efficacy of GABA at the receptor complex, (6) direction action on the chloride ionophore, and (7) inhibition of GABA reuptake. Examples of these approaches include the use of irreversible GABA-transaminase inhibitors, such as gamma-vinyl GABA, and the development of anticonvulsant beta-carbolines that interact with the "benzodiazepine receptor." Pharmacological mechanisms for diminishing excitatory transmission include (1) enzyme inhibitors that decrease the maximal rate of synthesis of glutamate or aspartate, (2) drugs that decrease the synaptic release of glutamate or aspartate, and (3) drugs that block the post-synaptic action of excitatory amino acids. Compounds that selectively antagonise excitation due to dicarboxylic amino acids have recently been developed. Those that selectively block excitation produced by N-methyl-D-aspartate (and aspartate) have proved to be potent anticonvulsants in many animal models of epilepsy. This provides a novel approach to the design of anticonvulsant drugs.
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
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.
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
Directory of Open Access Journals (Sweden)
S. Mohd. Joffry
2012-01-01
Full Text Available Melastoma malabathricum L. (Melastomataceae is one of the 22 species found in the Southeast Asian region, including Malaysia. Considered as native to tropical and temperate Asia and the Pacific Islands, this commonly found small shrub has gained herbal status in the Malay folklore belief as well as the Indian, Chinese, and Indonesian folk medicines. Ethnopharmacologically, the leaves, shoots, barks, seeds, and roots of M. malabathricum have been used to treat diarrhoea, dysentery, hemorrhoids, cuts and wounds, toothache, and stomachache. Scientific findings also revealed the wide pharmacological actions of various parts of M. malabthricum, such as antinociceptive, anti-inflammatory, wound healing, antidiarrheal, cytotoxic, and antioxidant activities. Various types of phytochemical constituents have also been isolated and identifed from different parts of M. malabathricum. Thus, the aim of the present review is to present comprehensive information on ethnomedicinal uses, phytochemical constituents, and pharmacological activities of M. malabathricum.
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
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.
Pharmacological stress agents in nuclear cardiology
International Nuclear Information System (INIS)
Buscombe, J.R.
2004-01-01
Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. However there are a group of patients who may not be able to undergo treadmill tests. Patients with underlying conditions like neuromuscular disease, musculoskeletal disorder, heart failure and end-stage renal disease (ESRD) on renal dialysis would find it difficult to perform exercise on a treadmill or bicycle ergometer. These conditions prevent them from performing adequate exercise. Such patients would benefit from pharmacological stress procedures combined with MPS. Nuclear medicine departments use various pharmacological agents while performing stress tests on cardiac patients. The most commonly used pharmacological agents for cardiac stress are coronary vasodilators and catecholamines. In addition to these agents, adjuvant use of nitrates and atropine is also a common practice in nuclear cardiology. This review addresses various physiological and pharmacological properties of the commonly used pharmacological stress agents in MPS and critically analyses their advantages and disadvantages, as well as their safety and efficacy. (author)
Directory of Open Access Journals (Sweden)
V. M. Tyurnikov
2012-01-01
Full Text Available Trigeminal neuralgia is a rare symptom of multiple sclerosis affecting the disability. Multiple sclerosis related trigeminal neuralgia has been attributed to a demyelinating lesion in the pons. When the adequate pain drug-relieve therapy is not possible or when the patient becomes refractory to the treatment or can not continue pharmacological treatment because of the side effects, surgical intervention, including percutaneous radiofrequency rhizotomy is being discussed. Literature review and the data upon the efficiency and safety of this neurosurgical treatment in 16 patients with multiple sclerosis have been analyzed. Percutaneous radiofrequency rhizotomy has been proved to be a safe, reproducible and effective method of the symptomatic surgical treatment of trigeminal neuralgia in patients with multiple sclerosis in cases of the intolerance/inefficiency of the pharmacological therapy.
Energy Technology Data Exchange (ETDEWEB)
Perez Guerra, Yohani; Molina Cuevas, Vivian; Oyarzabal Yera, Ambar; Mas Ferreiro, Rosa, E-mail: yohani.perez@cnic.edu.c [Centro de Productos Naturales, Centro Nacional de Investigaciones Cientificas (CNIC), La Habana (Cuba)
2011-07-01
Benign prostatic hyperplasia is a common disease in over 50 years-old men consisting in uncontrolled and benign growth of prostatic gland that leads to lower urinary tract symptoms. The etiology of benign prostatic hyperplasia is multifactoral involving the increased conversion of testosterone in dihydrotestosterone by the prostatic 5{alpha}-reductase action, which brought about events that encourage the prostate growth (static component) and the increase of the bladder and prostate smooth muscle tone (dynamic component) regulated by the a{alpha}{sub 1} -adrenoceptors (ADR). The pharmacological treatment of the benign prostatic hyperplasia includes the prostatic 5a{alpha}-reductase inhibitors, the a{alpha}{sub 1}-adrenoreceptor blockers, their combined therapy and the phytotherapy. This paper was aimed at presenting the most relevant aspects of the pharmacology of drugs used for treating the benign prostatic hyperplasia, and providing elements to analyze their efficacy, safety and tolerability. To this end, a review was made of the different drugs for the treatment of this pathology and they were grouped according to their mechanism of action. Natural products were included as lipid extracts from Serenoa repens and Pygeum africanum as well as D-004, a lipid extract from Roystonea regia fruits, with proved beneficial effects on the main etiological factors of benign prostatic hyperplasia. D-004 is a prostatic 5a-reductase inhibitor, an a{alpha}{sub 1}-adrenoceptor antagonist, a{alpha} 5-lipooxygenase inhibitor and has antioxidant action, all of which reveals a multifactoral mechanism. The results achieved till now indicate that D-004 is a safe and well-tolerated product
Lipid Peroxidation: Pathophysiology and Pharmacological Implications in the Eye
Directory of Open Access Journals (Sweden)
Ya Fatou eNjie-Mbye
2013-12-01
Full Text Available Oxygen-derived free radicals such as hydroxyl and hydroperoxyl species have been shown to oxidize phospholipids and other membrane lipid components leading to lipid peroxidation. In the eye, lipid peroxidation has been reported to play an important role in degenerative ocular diseases (age-related macular degeneration, cataract, glaucoma, diabetic retinopathy. Indeed, ocular tissues are prone to damage from reactive oxygen species due to stress from constant exposure of the eye to sunlight, atmospheric oxygen and environmental chemicals. Furthermore, free radical catalyzed peroxidation of long chain polyunsaturated acids (LCPUFAs such as arachidonic acid and docosahexaenoic acid leads to generation of LCPUFA metabolites including isoprostanes and neuroprostanes that may further exert pharmacological/toxicological actions in ocular tissues. Evidence from literature supports the presence of endogenous defense mechanisms against reactive oxygen species in the eye, thereby presenting new avenues for the prevention and treatment of ocular degeneration. Hydrogen peroxide (H2O2 and synthetic peroxides can exert pharmacological and toxicological effects on tissues of the anterior uvea of several mammalian species. There is evidence suggesting that the retina, especially retinal ganglion cells can exhibit unique characteristics of antioxidant defense mechanisms. In the posterior segment of the eye, H2O2 and synthetic peroxides produce an inhibitory action on glutamate release (using [3H]-D-aspartate as a marker, in vitro and on the endogenous glutamate and glycine concentrations in vivo. In addition to peroxides, isoprostanes can elicit both excitatory and inhibitory effects on norepinephrine (NE release from sympathetic nerves in isolated mammalian iris ciliary bodies. Whereas isoprostanes attenuate dopamine release from mammalian neural retina, in vitro, these novel arachidonic acid metabolites exhibit a biphasic regulatory effect on glutamate release
Directory of Open Access Journals (Sweden)
Lucius eCaviola
2015-12-01
Full Text Available We review work on the effectiveness of different forms of cognitive enhancement, both pharmacological and non-pharmacological. We consider caffeine, methylphenidate, and modafinil for pharmacological cognitive enhancement (PCE and computer training, physical exercise, and sleep for non-pharmacological cognitive enhancement (NPCE. We find that all of the techniques described can produce significant beneficial effects on cognitive performance. However, effect sizes are moderate, and consistently dependent on individual and situational factors as well as the cognitive domain in question. Although meta-analyses allowing a quantitative comparison of effectiveness across techniques are lacking to date, we can conclude that PCE is not more effective than NPCE. We discuss the physiological reasons for this limited effectiveness.We then propose that even though their actual effectiveness seems similar, in the general public PCE is perceived as fundamentally different from NPCE, in terms of effectiveness, but also in terms of acceptability. We illustrate the potential consequences such a misperception of PCE can have.
Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits
Walker, Andrew A.; Weirauch, Christiane; Fry, Bryan G.; King, Glenn F.
2016-01-01
The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools. PMID:26907342
Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits.
Walker, Andrew A; Weirauch, Christiane; Fry, Bryan G; King, Glenn F
2016-02-12
The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools.
Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits
Directory of Open Access Journals (Sweden)
Andrew A. Walker
2016-02-01
Full Text Available The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools.
A coarse-grained model for synergistic action of multiple enzymes on cellulose
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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
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).
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.
Molecular actions and clinical pharmacogenetics of lithium therapy
Can, Adem; Schulze, Thomas G.; Gould, Todd D.
2014-01-01
Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future. PMID:24534415
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…
Virtual Systems Pharmacology (ViSP software for mechanistic system-level model simulations
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Sergey eErmakov
2014-10-01
Full Text Available Multiple software programs are available for designing and running large scale system-level pharmacology models used in the drug development process. Depending on the problem, scientists may be forced to use several modeling tools that could increase model development time, IT costs and so on. Therefore it is desirable to have a single platform that allows setting up and running large-scale simulations for the models that have been developed with different modeling tools. We developed a workflow and a software platform in which a model file is compiled into a self-contained executable that is no longer dependent on the software that was used to create the model. At the same time the full model specifics is preserved by presenting all model parameters as input parameters for the executable. This platform was implemented as a model agnostic, therapeutic area agnostic and web-based application with a database back-end that can be used to configure, manage and execute large-scale simulations for multiple models by multiple users. The user interface is designed to be easily configurable to reflect the specifics of the model and the user’s particular needs and the back-end database has been implemented to store and manage all aspects of the systems, such as Models, Virtual Patients, User Interface Settings, and Results. The platform can be adapted and deployed on an existing cluster or cloud computing environment. Its use was demonstrated with a metabolic disease systems pharmacology model that simulates the effects of two antidiabetic drugs, metformin and fasiglifam, in type 2 diabetes mellitus patients.
Directory of Open Access Journals (Sweden)
Ming Hong
2017-03-01
Full Text Available Radix salviae miltiorrhizae (Danshen in Chinese, a classic traditional Chinese medicine (TCM herb, has been used for centuries to treat liver diseases. In this study, the preventive and curative potential of Danshen aqueous extract on acute/chronic alcoholic liver disease (ALD and non-alcoholic fatty liver disease (NAFLD was studied. The in vivo results indicated that Danshen could alleviate hepatic inflammation, fatty degeneration, and haptic fibrogenesis in ALD and NAFLD models. In the aspect of mechanism of action, the significant reduction in MDA levels in both ALD and NAFLD models implies the decreased levels of oxidative stress by Danshen. However, Danshen treatment could not activate the internal enzymatic antioxidant system in ALD and NAFLD models. To further explore the hepatoprotective mechanism of Danshen, an in silico-based network pharmacology approach was employed in the present study. The pharmacological network analysis result revealed that six potential active ingredients such as tanshinone iia, salvianolic acid b, and Danshensu may contribute to the hepatoprotective effects of Danshen on ALD and NAFLD. The action mechanism may relate with regulating the intracellular molecular targets such as PPARα, CYP1A2, and MMP2 for regulation of lipid metabolism, antioxidant and anti-fibrogenesis by these potential active ingredients. Our studies suggest that the combination of network pharmacology strategy with in vivo experimental study may provide a forceful tool for exploring the mechanism of action of traditional Chinese medicine (TCM herb and developing novel bioactive ingredients.
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.
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...
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.
[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.
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.
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.
New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy
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Betty Yuen Kwan Law
2016-03-01
Full Text Available Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM. For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri, Hu Zhang (Rhizoma polygoni cuspidati, Donglingcao (Rabdosia rubesens, Hou po (Cortex magnoliae officinalis and Chuan xiong (Rhizoma chuanxiong modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.
DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D
2013-10-01
Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P Kruskal-Wallis P < 0.001).
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
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.
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.
A short history of nitroglycerine and nitric oxide in pharmacology and physiology.
Marsh, N; Marsh, A
2000-04-01
1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with 'such precision'. Hering pursued NG ('glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of 'like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared '...a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of 'Monday disease' and of nitrate-withdrawal/overcompensation by 'Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador
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
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 ...
Pharmacological and therapeutic directions in ADHD: Specificity in the PFC
Directory of Open Access Journals (Sweden)
Levy Florence
2008-02-01
Full Text Available Abstract Background Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. Hypothesis The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA stimulation (through DAT transporter inhibition decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC, and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance
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…
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.
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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.
Mongalo, N I; McGaw, L J; Segapelo, T V; Finnie, J F; Van Staden, J
2016-12-24
The use of medicinal plants in the treatment of infections is ancient. A wide variety of ethnotherapeutic properties and pharmacological actions has been attributed to Terminalia sericea. Studies by various groups of investigators reveal that it is a multipurpose medicinal plant used mostly in the treatment of diarrhoea, sexually transmitted infections, skin rashes, tuberculosis and other infections. The current paper is aimed at providing an overview of the ethnomedicinal uses, toxicology, pharmacology and the phytochemistry of Terminalia sericea. Information was retrieved using various search engines, including Pubmed, Science Direct, Google Scholar, Scielo, SciFinder and Scopus. The key words used included Terminalia sericea, secondary metabolites, phytochemistry, biological activity, pharmacology, ethnobotanical survey, medicinal uses, safety, toxicology and other related words. Terminalia sericea is an important medicinal plant which possesses anti-HIV, anti-fungal, anti-bacterial, anticancer, lipolytic, wound healing, antiparasitic, anti-inflammatory and anti-oxidant activity, as the most valuable biological activities, thus lending pharmacological support to the plant's folkloric uses in indigenous medicine. Toxicologically, the extracts and isolated compounds from the plant species may have mild toxic effects. Phytochemically, the plant species possesses valuable compounds including triterpenes, alkaloids and flavonoids which may well contribute to its biological activity. Terminalia sericea contains secondary metabolites which are valuable in the treatment of a variety of human infections, including community acquired infections which may be prevalent in developing countries. The degree of toxicity reported in various extracts warrants further exploration of the cytotoxicity of the plant species, both against normal human cell lines and in vivo. Moreover, the acetylcholinesterase inhibitory and anti-inflammatory effects also need to be further
Pharmacological treatment of tics in Gilles de la Tourette Syndrome
Directory of Open Access Journals (Sweden)
Andrea E. Cavanna
2011-12-01
Full Text Available Tourette syndrome is a neurodevelopmental disorder characterised by the chronic presence of multiple motor tics (e.g. eye blinking, shoulder shrugging, etc. and at least one vocal/phonic tic (e.g. grunting or sniffing. The clinical picture of patients with Tourette syndrome is often complicated by tic-related behavioural problems and associated psychopathology. The pathophysiology of Tourette syndrome is poorly understood, however converging evidence from neuroimaging studies suggests abnormalities within the fronto-striatal pathways. The pharmacological management of the tic symptoms focuses on the dopaminergic and noradrenergic pathways and aims to improve the health-related quality of life of patients.
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.
Directory of Open Access Journals (Sweden)
Yan Li
2018-04-01
Full Text Available The balance and smooth shift between flexible, goal-directed behaviors and repetitive, habitual actions are critical to optimal performance of behavioral tasks. The striatum plays an essential role in control of goal-directed versus habitual behaviors through a rich interplay of the numerous neurotransmitters and neuromodulators to modify the input, processing and output functions of the striatum. The adenosine receptors (namely A2AR and A1R, with their high expression pattern in the striatum and abilities to interact and integrate dopamine, glutamate and cannabinoid signals in the striatum, may represent novel therapeutic targets for modulating instrumental behavior. In this study, we examined the effects of pharmacological blockade of the A2ARs and A1Rs on goal-directed versus habitual behaviors in different information processing phases of instrumental learning using a satiety-based instrumental behavior procedure. We found that A2AR antagonist acts at the coding, consolidation and expression phases of instrumental learning to modulate animals’ sensitivity to goal-directed valuation without modifying action-outcome contingency. However, pharmacological blockade and genetic knockout of A1Rs did not affect acquisition or sensitivity to goal-valuation of instrumental behavior. These findings provide pharmacological evidence for a potential therapeutic strategy to control abnormal instrumental behaviors associated with drug addiction and obsessive-compulsive disorder by targeting the A2AR.
Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.
Hsu, Ya-Hsin; Hsu, Yu-Ling; Liu, Sheng-Hung; Liao, Hsin-Chia; Lee, Po-Xuan; Lin, Chao-Hsiung; Lo, Lee-Chiang; Fu, Shu-Ling
2016-01-01
Andrographolide (ANDRO) is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD). ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90) and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.
Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.
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Ya-Hsin Hsu
Full Text Available Andrographolide (ANDRO is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD. ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90 and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.
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.
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.
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Yutaka eKoyama
2015-07-01
Full Text Available Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this article, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed.
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.
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.
Yokoyama, Hideaki; Kobayashi, Akio; Kondo, Kazuma; Oshida, Shin-Ichi; Takahashi, Tadakazu; Masuyama, Taku; Shoda, Toshiyuki; Sugai, Shoichiro
2018-01-01
Acyl CoA: diacylglycerol acyltransferase (DGAT) 1 is an enzyme that catalyzes the re-synthesis of triglycerides (TG) from free fatty acids and diacylglycerol. JTT-553 is a DGAT1 inhibitor and exhibits its pharmacological action (inhibition of re-synthesis of TG) in the enterocytes of the small intestine leading to suppression of a postprandial elevation of plasma lipids. After repeated oral dosing JTT-553 in rats and monkeys, plasma transaminase levels were increased but there were neither changes in other hepatic function parameters nor histopathological findings suggestive of hepatotoxicity. Based on the results of exploratory studies for investigation of the mechanism of the increase in transaminase levels, plasma transaminase levels were increased after dosing JTT-553 only when animals were fed after dosing and a main factor in the diet contributing to the increase in plasma transaminase levels was lipids. After dosing JTT-553, transaminase levels were increased in the small intestine but not in the liver, indicating that the origin of transaminase increased in the plasma was not the liver but the small intestine where JTT-553 exhibits its pharmacological action. The increase in small intestinal transaminase levels was due to increased enzyme protein synthesis and was suppressed by inhibiting fatty acid-transport to the enterocytes. In conclusion, the JTT-553-related increase in plasma transaminase levels is considered not to be due to release of the enzymes from injured cells into the circulation but to be phenomena resulting from enhancement of enzyme protein synthesis in the small intestine due to the pharmacological action of JTT-553 in this organ.
Wang, Ting; Guo, Rixin; Zhou, Guohong; Zhou, Xidan; Kou, Zhenzhen; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju
2016-07-21
Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng. Copyright © 2016
Review of the Chemistry and Pharmacology of 7-Methyljugulone ...
African Journals Online (AJOL)
Review of the Chemistry and Pharmacology of 7-Methyljugulone. ... Methods: The chemical and pharmacological data were retrieved from the well-known scientific websites such as Pubmed, Google Scholar, Reaxys, Scirus, Scopus, ... Keywords: 7-methyljugulone; biosynthesis; in vitro synthesis; pharmacology
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.
Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies.
Macoveanu, Julian
2014-03-27
Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions. Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor specific investigations to complement present research mainly focused on global serotonergic manipulations. Copyright © 2014 Elsevier B.V. All rights reserved.
Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review.
Guo, Rixin; Wang, Ting; Zhou, Guohong; Xu, Mengying; Yu, Xiankuo; Zhang, Xiao; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju
2018-01-01
Strychnos nux-vomica L. belongs to the genus Strychnos of the family Loganiaceae and grows in Sri Lanka, India and Australia. The traditional medicinal component is its seed, called Nux vomica. This study provides a relevant and comprehensive review of S. nux-vomica L., including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology, thus providing a foundation for future studies. Up to the present day, over 84 compounds, including alkaloids, iridoid glycosides, flavonoid glycosides, triterpenoids, steroids and organic acids, among others, have been isolated and identified from S. nux-vomica. These compounds possess an array of biological activities, including effects on the nervous system, analgesic and anti-inflammatory actions, antitumor effects, inhibition of the growth of pathogenic microorganisms and regulation of immune function. Furthermore, toxicity and detoxification methods are preliminarily discussed toward the end of this review. In further research on S. nux-vomica, bioactivity-guided isolation strategies should be emphasized. Its antitumor effects should be investigated further and in vivo animal experiments should be performed alongside in vitro testing. The pharmacological activity and toxicology of strychnine [Formula: see text]-oxide and brucine [Formula: see text]-oxide should be studied to explore the detoxification mechanism associated with processing more deeply.
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.
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.
Clinacanthus nutans: A review of the medicinal uses, pharmacology and phytochemistry.
Alam, Ariful; Ferdosh, Sahena; Ghafoor, Kashif; Hakim, Abdul; Juraimi, Abdul Shukor; Khatib, Alfi; Sarker, Zaidul I
2016-04-01
Clinacanthus nutans Lindau is known as snake grass belonging to the Acanthaceae family. This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes, insects and snake bites, lesions caused by herpes simplex virus, diabetes, and gout in Malaysia, Indonesia, Thailand and China. Phytochemical investigations documented the varied contents of bioactive compounds from this plant namely flavonoids, glycosides, glycoglycerolipids, cerebrosides and monoacylmonogalatosylglycerol. The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory, antiviral, antioxidant, and anti-diabetic activities. The findings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions. However, further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability for future drugs. This review summarizes the medicinal uses, phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.
Page, Nathaniel A.; Fung, Ho-Leung
2013-01-01
This review summarizes the major advances that had been reported since the outstanding contributions that Professor Benet and his group had made in the 1980’s and 1990’s concerning the metabolism and pharmacologic action of organic nitrates (ORN). Several pivotal studies have now enhanced our understanding of the metabolism and the bioactivation of ORN, resulting in the identification of a host of cysteine-containing enzymes that can carry out this function. Three isoforms of aldehyde dehydrogenase, all of which with active catalytic cysteine sites, are now known to metabolize, somewhat selectively, various members of the ORN family. The existence of a long-proposed but unstable thionitrate intermediate from organic nitrate metabolism has now been experimentally observed. ORN-induced thiol oxidation in multiple proteins, called the “Thionitrate Oxidation Hypothesis”, can be used not only to explain the phenomenon of nitrate tolerance, but also the various consequences of chronic nitrate therapy, viz., rebound vasoconstriction, and increased morbidity and mortality. Thus, a unifying biochemical hypothesis can account for the myriad of pharmacological events resulting from nitrate therapy. Optimization of future uses of ORN in cardiology and other diseases could benefit from further elaboration of this unifying hypothesis. PMID:23670666
Ionic channels underlying the ventricular action potential in zebrafish embryo.
Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar
2014-06-01
Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.
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.
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.
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.
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.
Clozapine-resistant schizophrenia – non pharmacological augmentation methods
Directory of Open Access Journals (Sweden)
Gałaszkiewicz Joanna
2017-12-01
Full Text Available Clozapine is the drug of choice for drug-resistant schizophrenia, but despite its use, 30-40% patients fail to achieve satisfactory therapeutic effects. In such situations, augmentation attempts are made by both pharmacological and non-pharmacological methods. To date, most of the work has been devoted to pharmacological strategies, much less to augemantation of clozapine with electroconvulsive therapy (C+ECT, transcranial direct current stimulation (tDCS or transcranial magnetic stimulation (TMS.
A Review of the Phytochemistry and Pharmacological Activities of Raphani Semen
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Tung-Ting Sham
2013-01-01
Full Text Available The dried ripe seed of Raphanus sativus L., commonly known as radish seed (or Raphani Semen, is used as traditional Chinese medicine (TCM to treat constipation, chronic tracheitis, and hypertension. The major active compounds in Raphani Semen are alkaloids, glucosinolates, brassinosteroids, and flavonoids. Fatty acids are its main nutritional contents. Raphani Semen has been demonstrated to have beneficial effects on hypertension, obesity, diabetes mellitus, constipation, and cough. So far, there is no report about the adverse/toxic effects of this herb on humans. However, Raphani Semen processed by roasting was reported to exhibit some adverse effects on mice. Additionally, erucic acid, the main fatty acid in Raphani Semen, was shown to enhance the toxicity of doxorubicin. Thus, Raphani Semen has a potential risk of causing toxicity and drug interaction. In summary, Raphani Semen is a valuable TCM herb with multiple pharmacological effects. More studies on Raphani Semen could help better understand its pharmacological mechanisms so as to provide clear scientific evidence to explain its traditional uses, to identify its therapeutic potential on other diseases, and to understand its possible harmful effects.
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.
Complex Pharmacology of Free Fatty Acid Receptors
DEFF Research Database (Denmark)
Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond
2017-01-01
pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...
[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.
Pharmacological Fingerprints of Contextual Uncertainty.
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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.
Directory of Open Access Journals (Sweden)
A. A. Mustafa
2016-01-01
Full Text Available The aim of this research is to provide some insights into the ability of the sixth year medical students and interns to recall theoretical knowledge of pharmacology. A cross-sectional study was conducted among students who graduated from three different medical schools in Riyadh, Saudi Arabia. A questionnaire was distributed to male and female students in 3 different colleges of medicine. The questionnaire included demographic information and ten multiple choice questions (MCQs on basic pharmacology. Out of the 161 students, there were 39 females (24% and 122 males (76%. A total of 36 (22% students studied at a traditional learning school whereas 125 (78% students studied at problem based learning (PBL schools. The students were recruited from three universities: KSU, KSAU-HS, and KFMC-COM. In general, 31 students (19% of the participants scored ≥ 7 out of 10, 77 students (48% of them obtained a correct score of (4–6 out of 10, and 53 students (33% scored less than 4. The study showed no statistically significant difference in recalling pharmacology between traditional school and problem based learning school except for those who prepared for exams. Results suggest that pharmacology is a difficult subject. Reevaluations are needed in the way of teaching pharmacology.
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.
Lin, Lin; Yang, Haifeng; Jones, Peter J H
2012-12-01
Fatty acid ethanolamides (FAE) represent a group of lipid signaling molecules associated with many physiological and pharmacological actions; however, low FAE tissue levels pose challenges in terms of analytical characterization. The objective was to develop a competent ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for analysis of multiple FAE in animal and human tissue samples. Analytes were extracted using lipid-phase and solid-phase extraction procedures. Chromatographic separation was achieved using a gradient elution in 8 min. FAE were quantified by MS/MS in positive electrospray ionization mode. Linearity was shown in lower and higher FAE concentration ranges, with a limit of quantification (LOQ) ≤0.2 ng/ml for FAE including alpha-linolenoylethanolamide (ALEA), arachidonoylethanolamide (AEA), docosahexaenoylethanolamide (DHEA), linoleoylethanolamide (LEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Accuracy was shown to be between 92.4% and 108.8%, and precision was <10% for all FAE species. In sum, this sensitive and reproducible method can be used to simultaneously determine multiple FAE at low concentrations in order to facilitate further study of the role of FAE on physiological state. Copyright © 2012 Elsevier Ltd. All rights reserved.
Ghrelin and Ghrelin Receptor Modulation of Psychostimulant Action
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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.
Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael
2015-10-01
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
Problems of pharmacological supply of disaster medicine
International Nuclear Information System (INIS)
Sabaev, V.V.; Il'ina, S.L.
1995-01-01
The paper reviews a number of pharmacological problems, being important for the disaster medicine, of theoretical and practical nature, the settlement of which would promote more efficient rendering emergency medical aid to the injured persons in the conditions of emergency situations and further expert medical care. On the example of radiation accidents there are studied methodical approaches to organization of drug prophylaxis and therapy of the injured persons in emergency situations. The authors have proved the necessity of arranging proper pharmacological supply of disaster medicine which is to settle the whole complex of scientific-applied and organizational questions relating to the competence of pharmacology and pharmacy. 17 refs
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.
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
Directory of Open Access Journals (Sweden)
Juliana Félix-Silva
2014-01-01
Full Text Available Jatropha gossypiifolia L. (Euphorbiaceae, widely known as “bellyache bush,” is a medicinal plant largely used throughout Africa and America. Several human and veterinary uses in traditional medicine are described for different parts and preparations based on this plant. However, critical reviews discussing emphatically its medicinal value are missing. This review aims to provide an up-to-date overview of the traditional uses, as well as the phytochemistry, pharmacology, and toxicity data of J. gossypiifolia species, in view of discussing its medicinal value and potential application in complementary and alternative medicine. Pharmacological studies have demonstrated significant action of different extracts and/or isolated compounds as antimicrobial, anti-inflammatory, antidiarrheal, antihypertensive, and anticancer agents, among others, supporting some of its popular uses. No clinical trial has been detected to date. Further studies are necessary to assay important folk uses, as well as to find new bioactive molecules with pharmacological relevance based on the popular claims. Toxicological studies associated with phytochemical analysis are important to understand the eventual toxic effects that could reduce its medicinal value. The present review provides insights for future research aiming for both ethnopharmacological validation of its popular use and its exploration as a new source of herbal drugs and/or bioactive natural products.
Pharmacology of new oral anticoagulants: mechanism of action, pharmacokinetics, pharmacodynamics
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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.
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.
Diclofenac: an update on its mechanism of action and safety profile.
Gan, Tong J
2010-07-01
Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA). Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate. This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug's pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety. Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are
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.
Learning a Mid-Level Representation for Multiview Action Recognition
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Cuiwei Liu
2018-01-01
Full Text Available Recognizing human actions in videos is an active topic with broad commercial potentials. Most of the existing action recognition methods are supposed to have the same camera view during both training and testing. And thus performances of these single-view approaches may be severely influenced by the camera movement and variation of viewpoints. In this paper, we address the above problem by utilizing videos simultaneously recorded from multiple views. To this end, we propose a learning framework based on multitask random forest to exploit a discriminative mid-level representation for videos from multiple cameras. In the first step, subvolumes of continuous human-centered figures are extracted from original videos. In the next step, spatiotemporal cuboids sampled from these subvolumes are characterized by multiple low-level descriptors. Then a set of multitask random forests are built upon multiview cuboids sampled at adjacent positions and construct an integrated mid-level representation for multiview subvolumes of one action. Finally, a random forest classifier is employed to predict the action category in terms of the learned representation. Experiments conducted on the multiview IXMAS action dataset illustrate that the proposed method can effectively recognize human actions depicted in multiview videos.
Stress Effects on Multiple Memory System Interactions
Ness, Deborah; Calabrese, Pasquale
2016-01-01
Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory syst...
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.
A minimal architecture for joint action
DEFF Research Database (Denmark)
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....
Pharmacological consequences of oxidative stress in ocular tissues
International Nuclear Information System (INIS)
Ohia, Sunny E.; Opere, Catherine A.; LeDay, Angela M.
2005-01-01
The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H 2 O 2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H 2 O 2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [ 3 H] D-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H 2 O 2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma
Pharmacological consequences of oxidative stress in ocular tissues
Energy Technology Data Exchange (ETDEWEB)
Ohia, Sunny E. [Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 141 Science and Research Building 2, University of Houston, Houston, TX 77204 (United States)]. E-mail: seohia@uh.edu; Opere, Catherine A. [Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE 68178 (United States); LeDay, Angela M. [Professional and Scientific Relations, Procter and Gamble Pharmaceuticals Inc., Mason, OH 45040 (United States)
2005-11-11
The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H{sub 2}O{sub 2} and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H{sub 2}O{sub 2} and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [{sup 3}H] D-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H{sub 2}O{sub 2} to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.
Non-pharmacological modulation of cerebral white matter organization
DEFF Research Database (Denmark)
Kristensen, Tina D; Mandl, Rene C W; Jepsen, Jens R M
2018-01-01
OBJECTIVE: Neuroplasticity is a well-described phenomenon, but effects of non-pharmacological interventions on white matter (WM) are unclear. Here we review associations between active non-pharmacological interventions and WM organization in healthy subjects and in psychiatric patients. METHOD...
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.
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.
Pharmacological receptors of nematoda as target points for action of antiparasitic drugs
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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. .
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...
Punishment, Pharmacological Treatment, and Early Release
DEFF Research Database (Denmark)
Ryberg, Jesper
2013-01-01
Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....
Biological and Pharmacological properties
Indian Academy of Sciences (India)
First page Back Continue Last page Overview Graphics. Biological and Pharmacological properties. NOEA inhibits Ceramidase. Anandamide inhibits gap junction conductance and reduces sperm fertilizing capacity. Endogenous ligands for Cannabinoid receptors (anandamide and NPEA). Antibacterial and antiviral ...
Non-pharmacological approaches to alleviate distress in dementia care.
Mitchell, Gary; Agnelli, Joanne
2015-11-25
Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature.
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...
Pharmacological Experimental Study Of The Anti-Depressant Effect ...
African Journals Online (AJOL)
Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...
Temporal trends in pharmacology publications by pharmacy institutes: A deeper dig
Bhatt, Parloop Amit; Patel, Zarana
2016-01-01
Objective: Publications in Indian Journal of Pharmacology (IJP) are the face of contemporary pharmacology practices followed in health-care profession - a knowledge-based profession. It depicts trends in terms of quantity (proportions), quality, type (preclinical/clinical), thrust areas, etc., of pharmacology followed by biomedical community professions both nationally and internationally. This article aims to establish temporal trends in pharmacology research by pharmacy institutes in light ...
Burry, L D; Hutton, B; Guenette, M; Williamson, D; Mehta, S; Egerod, I; Kanji, S; Adhikari, N K; Moher, D; Martin, C M; Rose, L
2016-09-08
will address the existing knowledge gap regarding best practices for delirium prevention in critically ill adults by synthesizing evidence from trials of pharmacological, non-pharmacological, and multi-component interventions administered in or prior to transfer to the ICU. Use of network meta-analysis will clarify which delirium prevention strategies are most effective in improving clinical outcomes while causing least harm. The network meta-analysis is a novel approach and will provide knowledge users and decision makers with comparisons of multiple interventions of delirium prevention strategies. PROSPERO CRD42016036313.
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.
Online Evolution for Multi-Action Adversarial Games
Justesen, Niels; Mahlmann, Tobias; Togelius, Julian
2016-01-01
We present Online Evolution, a novel method for playing turn-based multi-action adversarial games. Such games, which include most strategy games, have extremely high branching factors due to each turn having multiple actions. In Online Evolution, an evolutionary algorithm is used to evolve the combination of atomic actions that make up a single move, with a state evaluation function used for fitness. We implement Online Evolution for the turn-based multi-action game Hero Academy and compare i...
Directory of Open Access Journals (Sweden)
Majid Almadi
2009-01-01
Full Text Available The present article describes three difficult cases of recurrent bleeding from obscure causes, followed by a review of the pitfalls and pharmacological management of obscure gastrointestinal bleeding. All three patients underwent multiple investigations. An intervening complicating diagnosis or antiplatelet drugs may have compounded long-term bleeding in two of the cases. A bleeding angiodysplasia was confirmed in one case but was aggravated by the need for anticoagulation. After multiple transfusions and several attempts at endoscopic management in some cases, long-acting octreotide was associated with decreased transfusion requirements and increased hemoglobin levels in all three cases, although other factors may have contributed in some. In the third case, however, the addition of low-dose thalidomide stopped bleeding for a period of at least 23 months.
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
Traumatic brain injury pharmacological treatment: recommendations
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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.
International Nuclear Information System (INIS)
Dimopoulou, Myrto; Verhoef, Aart; Pennings, Jeroen L.A.; Ravenzwaay, Bennard van; Rietjens, Ivonne M.C.M.; Piersma, Aldert H.
2017-01-01
Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID 10 (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants. • Retinoic
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Dimopoulou, Myrto, E-mail: myrto.dimopoulou@wur.nl [Division of Toxicology, Wageningen University (Netherlands); National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Pennings, Jeroen L.A. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Ravenzwaay, Bennard van [Division of Toxicology, Wageningen University (Netherlands); BASF SE, Experimental Toxicology and Ecology, Ludwigshafen (Germany); Rietjens, Ivonne M.C.M. [Division of Toxicology, Wageningen University (Netherlands); Piersma, Aldert H. [National Institute of Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Utrecht University, Utrecht (Netherlands)
2017-05-01
Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48 h. The compounds tested showed embryotoxicity in a dose-response fashion. Functional analysis of differential gene expression after 4 h exposure at the ID{sub 10} (effective dose for 10% decreased TMS), revealed the sterol biosynthesis pathway and embryonic development genes, dominated by genes in the retinoic acid (RA) pathway, albeit in a differential way. Flusilazole, ketoconazole and triadimefon were the most potent compounds affecting the RA pathway, while in terms of regulation of sterol function, difenoconazole and ketoconazole showed the most pronounced effects. Dose-dependent analysis of the effects of flusilazole revealed that the RA pathway related genes were already differentially expressed at low dose levels while the sterol pathway showed strong regulation at higher embryotoxic doses, suggesting that this pathway is less predictive for the observed embryotoxicity. A similar analysis at the 24-hour time point indicated an additional time-dependent difference in the aforementioned pathways regulated by flusilazole. In summary, the rat WEC assay in combination with transcriptomics could add a mechanistic insight into the embryotoxic potency ranking and pharmacological mode of action of the tested compounds. - Highlights: • Embryonic exposure to azoles revealed concentration-dependent malformations. • Transcriptomics could enhance the mechanistic knowledge of embryotoxicants.
Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.
Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne
2017-11-01
In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
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
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
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.
Directory of Open Access Journals (Sweden)
Katrin M Hoffmann
2016-07-01
Full Text Available Kampo medicine is a form of Japanese phytotherapy originating from traditional Chinese medicine (TCM. During the last several decades, much attention has been paid to the pharmacological effects of these medical plants and its constituents. However, in many cases, a systematic screening of Kampo remedies to determine pharmacologically relevant targets is still lacking. In this study, we performed a broad screening of Kampo remedies to look for pharmacologically relevant 5 HT3A and GABA(A receptor ligands. Several of the Kampo remedies are currently used for symptoms such as nausea, emesis, gastrointestinal motility disorders, anxiety, restlessness or insomnia. Therefore, we analyzed the pharmacological effects of 121 herbal drugs from Kampo medicine as ethanol tinctures on heterologously expressed 5 HT3A and GABA(A receptors, due to the involvement of these receptors in such pathophysiological processes. The tinctures of Lindera aggregata (radix and Leonurus japonicus (herba were the most effective inhibitory compounds on the 5 HT3A receptor. Further investigation of known ingredients in these compounds led to the identification of leonurine from Leonurus as a new natural 5 HT3A receptor antagonist. We also identified several potentiating herbs (e.g., Magnolia officinalis (cortex, Syzygium aromaticum (flos and Panax ginseng (radix for the GABAA receptor, which are all traditionally used for their sedative or anxiolytic effects. A variety of tinctures with antagonistic effects, for instance Salvia miltiorrhiza (radix were also detected. Therefore, this study reveals new insights into the pharmacological action of a broad spectrum of herbal drugs from Kampo, allowing a better understanding of their physiological effects and clinical applications.
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.
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Maritza Dorila Placencia Medina
2015-09-01
Full Text Available ABSTRACT The use of virtual simulation allows students to interactive learning with creativity and clarity in the theoretical foundation of the pharmacokinetics and pharmacodynamics of the drugs used in pharmacology. Objective: Know the level of satisfaction of students in the design and implementation of virtual simulation laboratory in the Department of Pharmacology, Faculty of Medicine of San Marcos Material and Methods: Descriptive, qualitative study of research-action type. The design and implementation of a virtual simulation laboratory, the intervention of improvement and perfection of teaching materials for the development of practical section of Pharmacology, Faculty of Medicine of San Marcos was planned, using the software Microlab® and CV Rat. A survey of user satisfaction virtual laboratory technique the interview was conducted, as an instrument, using a Likert scale of minimum satisfaction starting in 1 to maximum of 10. Sample size of 26 students. Results: A new process was implemented teaching - learning of Experimental Pharmacology Laboratory using virtual simulation. Most students in the virtual classroom lab have a satisfaction level 9-10 / 10 on the Likert scale. Conclusions: The virtual simulation laboratory Section of Pharmacology got a good level of satisfaction among students.
Phage Therapy: Eco-Physiological Pharmacology
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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.
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Revati eWani
2014-10-01
Full Text Available The perception of reactive oxygen species (ROS has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g. cancer. New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically-distinct alterations to the protein (e.g. sulfenic/sulfinic/sulfonic acid, disulfides. These post-translational modifications (PTM are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.
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
de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro
2017-04-01
D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.
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Leszek Bober
2012-05-01
Full Text Available Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model method and the literature values of biological activity (antiproliferative for the A431 cells expressed as LD50 of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.
Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan
2017-11-08
LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Directory of Open Access Journals (Sweden)
Ferrán Catalá-López
showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia, but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution.Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.
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.
Yingmin Zhu; Haijun Chen; Stephen Boulton; Fang Mei; Na Ye; Giuseppe Melacini; Jia Zhou; Xiaodong Cheng
2015-01-01
The cAMP signaling cascade is one of the most frequently targeted pathways for the development of pharmaceutics. A plethora of recent genetic and pharmacological studies suggest that exchange proteins directly activated by cAMP (EPACs) are implicated in multiple pathologies. Selective EPAC inhibitors have been recently developed. One specific inhibitor, ESI-09, has been shown to block EPAC activity and functions, as well as to recapitulate genetic phenotypes of EPAC knockout mice when applied...
Keijsers, Carolina J P W; van Hensbergen, Larissa; Jacobs, Lotte; Brouwers, Jacobus R B J; de Wildt, Dick J; ten Cate, Olle Th J; Jansen, Paul A F
2012-01-01
AIMS Given the reported high rates of medication errors, especially in elderly patients, we hypothesized that current curricula do not devote enough time to the teaching of geriatric pharmacology. This review explores the quantity and nature of geriatric pharmacology education in undergraduate and postgraduate curricula for health professionals. METHODS Pubmed, Embase and PsycINFO databases were searched (from 1 January 2000 to 11 January 2011), using the terms ‘pharmacology’ and ‘education’ in combination. Articles describing content or evaluation of pharmacology education for health professionals were included. Education in general and geriatric pharmacology was compared. RESULTS Articles on general pharmacology education (252) and geriatric pharmacology education (39) were included. The number of publications on education in general pharmacology, but not geriatric pharmacology, has increased over the last 10 years. Articles on undergraduate and postgraduate education for 12 different health disciplines were identified. A median of 24 h (from 15 min to 4956 h) devoted to pharmacology education and 2 h (1–935 h) devoted to geriatric pharmacology were reported. Of the articles on education in geriatric pharmacology, 61.5% evaluated the teaching provided, mostly student satisfaction with the course. The strength of findings was low. Similar educational interventions were not identified, and evaluation studies were not replicated. CONCLUSIONS Recently, interest in pharmacology education has increased, possibly because of the high rate of medication errors and the recognized importance of evidence-based medical education. Nevertheless, courses on geriatric pharmacology have not been evaluated thoroughly and none can be recommended for use in training programmes. Suggestions for improvements in education in general and geriatric pharmacology are given. PMID:22416832
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...
Systems Pharmacology in Small Molecular Drug Discovery
Directory of Open Access Journals (Sweden)
Wei Zhou
2016-02-01
Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.
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
Cell-based therapeutic strategies for multiple sclerosis
DEFF Research Database (Denmark)
Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C
2017-01-01
and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities......, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved...
Pharmacological characterization of social isolation-induced hyperactivity
DEFF Research Database (Denmark)
Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders
2011-01-01
Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia.......Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia....
Sauer, Kristin; Kemper, Claudia; Glaeske, Gerd
2011-01-01
Fibromyalgia syndrome (FMS) is a chronic pain condition impacting on quality of life, causing physical and psychological impairment resulting in limited participation in professional and social life. The objective of this study was to assess the prevalence, recommended pharmacological and non-pharmacological interventions of FMS, patients' characteristics and to compare findings to current research. About 1.6 Mio patients of a German statutory health insurance company (GEK) in 2007 were analyzed for: (a) the prevalence of FMS (ICD-10: M79.7); (b) and comorbid depression (ICD-10: F32/33); (c) the recommended pharmacological and non-pharmacological intervention rates; (d) and characteristics of patients associated with being prescribed recommended interventions. The (a) standardized prevalence of FMS in 2007 was 0.05% in men and 0.4% in women. (b) 51.9% of the patients with prevalent FMS had a comorbid depression in 2007 (88.2% female). (c) 66% of FMS patients received the recommended pharmacological treatment, 59% physical therapy, 6.1% cognitive-behavioural therapy and 3.4% a combination of these (multi-component therapy, MCT). (d) One year increase in age was associated with a 3% decrease in the predicted odds of receiving MCT (95%, CI 0.95-0.99). The current data indicate an FMS-prevalence that differs from epidemiological surveys and screenings, probably due to methodological differences. Especially females with comorbid depression are affected. The likelihood of receiving MCT is not associated with gender, but with younger age. Yet, the findings seem to indicate insufficient and inadequate treatment, but FMS warrants more research. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Pharmacological intervention with oxidative burst in human neutrophils
Czech Academy of Sciences Publication Activity Database
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
Veterinary pharmacology: history, current status and future prospects.
Lees, P; Fink-Gremmels, J; Toutain, P L
2013-04-01
Veterinary therapeutics, based on the art of Materia Medica, has been practised for countless centuries, but the science of veterinary pharmacology is of very recent origin. This review traces the contribution of Materia Medica to veterinary therapeutics from the Egyptian period through to the Age of Enlightenment. The first tentative steps in the development of the science of veterinary pharmacology were taken in the 18th century, but it was not until the mid 20th century that the science replaced the art of Materia Medica. This review traces the 20th century developments in veterinary pharmacology, with emphasis on the explosion of knowledge in the 35 year period to 2010. The range of factors which have influenced the current status of the discipline are reviewed. Future developments are considered from the perspectives of what might be regarded as desirable and those innovations that might be anticipated. We end with words of encouragement for young colleagues intent upon pursuing a career in veterinary pharmacology. © 2013 Blackwell Publishing Ltd.
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
Dos Santos, Cintia Miranda; Campos, Jaqueline Ferreira; Dos Santos, Helder Freitas; Balestieri, José Benedito Perrella; Silva, Denise Brentan; de Picoli Souza, Kely; Carollo, Carlos Alexandre; Estevinho, Leticia M; Dos Santos, Edson Lucas
2017-01-01
Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae . The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.
Directory of Open Access Journals (Sweden)
Cintia Miranda dos Santos
2017-01-01
Full Text Available Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae. The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.
Ganguly, Pronab; Soliman, Abdrabo; Moustafa, Ahmed A
2018-01-01
Individuals with schizophrenia lead a poor quality of life, due to poor medical attention, homelessness, unemployment, financial constraints, lack of education, and poor social skills. Thus, a review of factors associated with the holistic management of schizophrenia is of paramount importance. The objective of this review is to improve the quality of life of individuals with schizophrenia, by addressing the factors related to the needs of the patients and present them in a unified manner. Although medications play a role, other factors that lead to a successful holistic management of schizophrenia include addressing the following: financial management, independent community living, independent living skill, relationship, friendship, entertainment, regular exercise for weight gained due to medication administration, co-morbid health issues, and day-care programmes for independent living. This review discusses the relationship between different symptoms and problems individuals with schizophrenia face (e.g., homelessness and unemployment), and how these can be managed using pharmacological and non-pharmacological methods. Thus, the target of this review is the carers of individuals with schizophrenia, public health managers, counselors, case workers, psychiatrists, and clinical psychologists aiming to enhance the quality of life of individuals with schizophrenia.
DEFF Research Database (Denmark)
Brøsen, Kim; Andersen, Stig Ejdrup; Borregaard, Jeanett
2016-01-01
new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors...
Corn silk (Stigma maydis) in healthcare: a phytochemical and pharmacological review.
Hasanudin, Khairunnisa; Hashim, Puziah; Mustafa, Shuhaimi
2012-08-13
Corn silk (Stigma maydis) is an important herb used traditionally by the Chinese, and Native Americans to treat many diseases. It is also used as traditional medicine in many parts of the world such as Turkey, United States and France. Its potential antioxidant and healthcare applications as diuretic agent, in hyperglycemia reduction, as anti-depressant and anti-fatigue use have been claimed in several reports. Other uses of corn silk include teas and supplements to treat urinary related problems. The potential use is very much related to its properties and mechanism of action of its plant's bioactive constituents such as flavonoids and terpenoids. As such, this review will cover the research findings on the potential applications of corn silk in healthcare which include its phytochemical and pharmacological activities. In addition, the botanical description and its toxicological studies are also included.
Directory of Open Access Journals (Sweden)
Luiza R. Nazario
2017-11-01
Full Text Available Parkinson's disease (PD is one of the most prevalent neurodegenerative disease displaying negative impacts on both the health and social ability of patients and considerable economical costs. The classical anti-parkinsonian drugs based in dopaminergic replacement are the standard treatment, but several motor side effects emerge during long-term use. This mini-review presents the rationale to several efforts from pre-clinical and clinical studies using adenosine receptor antagonists as a non-dopaminergic therapy. As several studies have indicated that the monotherapy with adenosine receptor antagonists reaches limited efficacy, the usage as a co-adjuvant appeared to be a promising strategy. The formulation of multi-targeted drugs, using adenosine receptor antagonists and other neurotransmitter systems than the dopaminergic one as targets, have been receiving attention since Parkinson's disease presents a complex biological impact. While pharmacological approaches to cure or ameliorate the conditions of PD are the leading strategy in this area, emerging positive aspects have arisen from non-pharmacological approaches and adenosine function inhibition appears to improve both strategies.
Managing bay and estuarine ecosystems for multiple services
Needles, Lisa A.; Lester, Sarah E.; Ambrose, Richard; Andren, Anders; Beyeler, Marc; Connor, Michael S.; Eckman, James E.; Costa-Pierce, Barry A.; Gaines, Steven D.; Lafferty, Kevin D.; Lenihan, Junter S.; Parrish, Julia; Peterson, Mark S.; Scaroni, Amy E.; Weis, Judith S.; Wendt, Dean E.
2013-01-01
Managers are moving from a model of managing individual sectors, human activities, or ecosystem services to an ecosystem-based management (EBM) approach which attempts to balance the range of services provided by ecosystems. Applying EBM is often difficult due to inherent tradeoffs in managing for different services. This challenge particularly holds for estuarine systems, which have been heavily altered in most regions and are often subject to intense management interventions. Estuarine managers can often choose among a range of management tactics to enhance a particular service; although some management actions will result in strong tradeoffs, others may enhance multiple services simultaneously. Management of estuarine ecosystems could be improved by distinguishing between optimal management actions for enhancing multiple services and those that have severe tradeoffs. This requires a framework that evaluates tradeoff scenarios and identifies management actions likely to benefit multiple services. We created a management action-services matrix as a first step towards assessing tradeoffs and providing managers with a decision support tool. We found that management actions that restored or enhanced natural vegetation (e.g., salt marsh and mangroves) and some shellfish (particularly oysters and oyster reef habitat) benefited multiple services. In contrast, management actions such as desalination, salt pond creation, sand mining, and large container shipping had large net negative effects on several of the other services considered in the matrix. Our framework provides resource managers a simple way to inform EBM decisions and can also be used as a first step in more sophisticated approaches that model service delivery.
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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.
Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review
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Paulo Michel P. Ferreira
2011-12-01
Full Text Available Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X and casearvestrins (A-C, compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente
Radioreceptor assay: theory and applications to pharmacology
International Nuclear Information System (INIS)
Perret, G.; Simon, P.
1984-01-01
The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproductibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, β-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising [fr
Evaluating pharmacological models of high and low anxiety in sheep
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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
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Alexey P. Sarapultsev
2016-05-01
Full Text Available Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985, and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction.
A Multi-Level Analysis of World Scientific Output in Pharmacology
Olmeda-Gómez, Carlos; Ovalle-Perandones, María Antonia; Perianes-Rodríguez, Antonio
2012-01-01
The purpose of this chapter is to analyse international research in “pharmacology, toxicology and pharmaceutics” (hereafter pharmacology) on the basis of the scientific papers listed in the Scopus multidisciplinary database. This primary objective is reached by answering the following questions (in the section on results). What weight does the subject area “pharmacology, toxicology and pharmaceutics” carry in world-wide science? What is the percentage contribution made by the various regions ...
Pharmacological enhancement of treatment for amblyopia
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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
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
Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P
2012-10-01
Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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Alfred Maroyi
2018-05-01
Full Text Available Syzygium cordatum is a valuable medicinal plant in the materia medica of east and southern Africa. The aim of this study was to review the botany, medicinal uses, phytochemistry and ethnopharmacological properties of S. cordatum. Relevant literature search was carried out using internet sources such as ACS, Web of Science, Wiley, SpringerLink, Scopus, Mendeley, Google Scholar, Pubmed, SciFinder, BioMed Central, Science Direct and Elsevier. Other literature sources were conference papers, book chapters, books, theses and websites. The leaves, roots, bark and fruits of S. cordatum are used as ethnomedicines against 24 human diseases such as gastro-intestinal disorders, burns, sores, wounds, colds, cough, respiratory complaints, sexually transmitted infections (STIs, tuberculosis, fever and malaria. Several phytochemical compounds including alkaloids, anthocyanidin, essential oils, flavonoids, leucoanthocyanidin, phenols, phytosterols, saponins, simple sugars, terpenoids and triterpenoid have been identified from S. cordatum. Pharmacological evaluations revealed that S. cordatum is characterized by several biological activities including antibacterial, antifungal, antidiarrheal, anti-sexually transmitted infections, antidiabetic, anticholinesterase, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial and anti-proteus. These pharmacological findings lend credence to the traditional ethnomedicinal uses and ethnopharmacological importance of S. cordatum. Future research on the species should identify the biological compounds, their mode of action and physiological pathways and clinical relevance.
Nanobody-Enabled Reverse Pharmacology on G-Protein-Coupled Receptors.
Pardon, Els; Betti, Cecilia; Laeremans, Toon; Chevillard, Florent; Guillemyn, Karel; Kolb, Peter; Ballet, Steven; Steyaert, Jan
2018-05-04
The conformational complexity of transmembrane signaling of G-protein-coupled receptors (GPCRs) is a central hurdle for the design of screens for receptor agonists. In their basal states, GPCRs have lower affinities for agonists compared to their G-protein-bound active state conformations. Moreover, different agonists can stabilize distinct active receptor conformations and do not uniformly activate all cellular signaling pathways linked to a given receptor (agonist bias). Comparative fragment screens were performed on a β 2 -adrenoreceptor-nanobody fusion locked in its active-state conformation by a G-protein-mimicking nanobody, and the same receptor in its basal-state conformation. This simple biophysical assay allowed the identification and ranking of multiple novel agonists and permitted classification of the efficacy of each hit in agonist, antagonist, or inverse agonist categories, thereby opening doors to nanobody-enabled reverse pharmacology. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
Multiple modes of action potential initiation and propagation in mitral cell primary dendrite
DEFF Research Database (Denmark)
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...
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…
Granica, Sebastian; Piwowarski, Jakub P; Czerwińska, Monika E; Kiss, Anna K
2014-10-28
beneficial effect for this disorder, but the number of in vitro studies is not sufficient and the in vivo studies are not conclusive or too preliminary to draw a final conclusion about the efficacy of Epilobium preparations. More in vitro, in vivo and clinical studies to confirm this mode of action are strongly needed. Epilobium's extracts have also documented antioxidative and potential anti-inflammatory properties. Oenothein B can be considered as responsible for some of Epilobium pharmacological properties. Because of the lack of clinical data further studies are needed to provide an evidence base for traditional uses of plant materials belonging to the Epilobium genus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Directory of Open Access Journals (Sweden)
von Wolff Alessa
2010-11-01
Full Text Available Abstract Background Chronic depressions represent a substantial part of depressive disorders and are associated with severe consequences. Several studies were performed addressing the effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depressions. Yet, a systematic review comparing the effectiveness of multiple treatment options and considering all subtypes of chronic depressions is still missing. Methods/Design Aim of this project is to summarize empirical evidence on efficacy and effectiveness of treatments for chronic depression by means of a systematic review. The primary objectives of the study are to examine, which interventions are effective; to examine, if any differences in effectiveness between active treatment options exist; and to find possible treatment effect modifiers. Psychotherapeutic, pharmacological, and combined treatments will be considered as experimental interventions and no treatment, wait-list, psychological/pharmacological placebo, treatment as usual, and other active treatments will be seen as comparators. The population of patients will include adults with chronic major depression, dysthymia, double depression, or recurrent depression without complete remission between episodes. Outcomes of the analyses are depressive symptoms, associated consequences, adverse events, and study discontinuation. Only randomized controlled trials will be considered. Discussion Given the high prevalence and serious consequences of chronic depression and a considerable amount of existing primary studies addressing the effectiveness of different treatments the present systematic review may be of high relevance. Special attention will be given to the use of current methodological standards. Findings are likely to provide crucial information that may help clinicians to choose the appropriate treatment for chronically depressed patients.
Comer, Sandra D.; Bickel, Warren K.; Yi, Richard; de Wit, Harriet; Higgins, Stephen T.; Wenger, Galen R.; Johanson, Chris-Ellyn; Kreek, Mary Jeanne
2010-01-01
A symposium held at the 50th annual meeting of the Behavioral Pharmacology Society in May 2007 reviewed progress in the human behavioral pharmacology of drug abuse. Studies on drug self-administration in humans are reviewed that assessed reinforcing and subjective effects of drugs of abuse. The close parallels observed between studies in humans and laboratory animals using similar behavioral techniques have broadened our understanding of the complex nature of the pharmacological and behavioral factors controlling drug self-administration. The symposium also addressed the role that individual differences, such as gender, personality, and genotype play in determining the extent of self-administration of illicit drugs in human populations. Knowledge of how these factors influence human drug self-administration has helped validate similar differences observed in laboratory animals. In recognition that drug self-administration is but one of many choices available in the lives of humans, the symposium addressed the ways in which choice behavior can be studied in humans. These choice studies in human drug abusers have opened up new and exciting avenues of research in laboratory animals. Finally, the symposium reviewed behavioral pharmacology studies conducted in drug abuse treatment settings and the therapeutic benefits that have emerged from these studies. PMID:20664330
Action and Organizational Learning in an Elevator Company
De Loo, Ivo
2006-01-01
Purpose: To highlight the relevance of management control in action learning programs that aim to foster organizational learning. Design/methodology/approach: Literature review plus case study. The latter consists of archival analysis and multiple interviews. Findings: When action learning programs are built around singular learning experiences,…
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)
Shahid, Mohammad; Shahzad Cheema, Muhammad; Klenner, Alexander; Younesi, Erfan; Hofmann-Apitius, Martin
2013-03-01
Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Moreno-Galindo, Eloy G; Sanchez-Chapula, Jose A; Tristani-Firouzi, Martin; Navarro-Polanco, Ricardo A
2016-09-01
Potassium (K(+)) channels are crucial for determining the shape, duration, and frequency of action-potential firing in excitable cells. Broadly speaking, K(+) channels can be classified based on whether their macroscopic current outwardly or inwardly rectifies, whereby rectification refers to a change in conductance with voltage. Outwardly rectifying K(+) channels conduct greater current at depolarized membrane potentials, whereas inward rectifier channels conduct greater current at hyperpolarized membrane potentials. Under most circumstances, outward currents through inwardly rectifying K(+) channels are reduced at more depolarized potentials. However, the acetylcholine-gated K(+) channel (KACh) conducts current that inwardly rectifies when activated by some ligands (such as acetylcholine), and yet conducts current that outwardly rectifies when activated by other ligands (for example, pilocarpine and choline). The perplexing and paradoxical behavior of KACh channels is due to the intrinsic voltage sensitivity of the receptor that activates KACh channels, the M2 muscarinic receptor (M2R). Emerging evidence reveals that the affinity of M2R for distinct ligands varies in a voltage-dependent and ligand-specific manner. These intrinsic receptor properties determine whether current conducted by KACh channels inwardly or outwardly rectifies. This review summarizes the most recent concepts regarding the intrinsic voltage sensitivity of muscarinic receptors and the consequences of this intriguing behavior on cardiac physiology and pharmacology of KACh channels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Rimland, Joseph M.; Abraha, Iosief; Dell’Aquila, Giuseppina; Cruz-Jentoft, Alfonso; Soiza, Roy; Gudmusson, Adalsteinn; Petrovic, Mirko; O’Mahony, Denis; Todd, Chris; Cherubini, Antonio
2016-01-01
Background Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. Objectives To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. Methods We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. Results Fifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. Conclusions The aim of this overview of
Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department
Directory of Open Access Journals (Sweden)
E. Sánchez Gómez
2014-07-01
Full Text Available Abstract: Objective: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. Material and methods: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE® and EMBASE® (with the filer language English or Spanish, and the descriptors: “name of the anti-cancer drug” AND (“drug interactions” OR “pharmacokinetic”, Up-to-date®, MICROMEDEX® and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction-free alternative was sought. Results: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts and Hypericum perforatum. Conclusions: Oral anticancer drugs have numerous pharmacologic
Pharmacological Treatment for Atrial Fibrillation
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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.
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.
Impediments to the success of management actions for species recovery.
Directory of Open Access Journals (Sweden)
Chooi Fei Ng
Full Text Available Finding cost-effective management strategies to recover species declining due to multiple threats is challenging, especially when there are limited resources. Recent studies offer insights into how costs and threats can influence the best choice of management actions. However, when implementing management actions in the real-world, a range of impediments to management success often exist that can be driven by social, technological and land-use factors. These impediments may limit the extent to which we can achieve recovery objectives and influence the optimal choice of management actions. Nonetheless, the implications of these impediments are not well understood, especially for recovery planning involving multiple actions. We used decision theory to assess the impact of these types of impediments for allocating resources among recovery actions to mitigate multiple threats. We applied this to a declining koala (Phascolarctos cinereus population threatened by habitat loss, vehicle collisions, dog attacks and disease. We found that the unwillingness of dog owners to restrain their dogs at night (a social impediment, the effectiveness of wildlife crossings to reduce vehicle collisions (a technological impediment and the unavailability of areas for restoration (a land-use impediment significantly reduced the effectiveness of our actions. In the presence of these impediments, achieving successful recovery may be unlikely. Further, these impediments influenced the optimal choice of recovery actions, but the extent to which this was true depended on the target koala population growth rate. Given that species recovery is an important strategy for preserving biodiversity, it is critical that we consider how impediments to the success of recovery actions modify our choice of actions. In some cases, it may also be worth considering whether investing in reducing or removing impediments may be a cost-effective course of action.
Florez, Diego Hernando Ângulo; Dos Santos Moreira, Ana Maria; da Silva, Pedro Rafael; Brandão, Ricardo; Borges, Marcella Matos Cordeiro; de Santana, Fernando José Malagueño; Borges, Keyller Bastos
2017-04-01
"Krokodil" or "Crocodile" is an illegal homemade desomorphine drug obtained from chemical reactions of commercial codeine drugs with several other powerful and highly toxic chemical agents increasing its addiction and hallucinogenic effects when compared with other morphine analogues. This paper summarizes a complete review about an old drug called desomorphine (Krokodil), presenting its chemistry, pharmacology, metabolism, toxicology and analysis. It is of particular interest and concern because this cheaper injectable semisynthetic opioid drug has been largely used in recent years for recreational purposes in several Eastern European as well as North and South American countries, despite known damage to health that continuous use might induce. These injuries are much stronger and more aggressive than morphine's, infecting and rotting skin and soft tissue to the bone of addicts at the point of injection in less than three years, which, in most cases, evolves to death. On this basis, it is imperative that literature reviews focus on the chemistry, pharmacology, toxicology and analysis of dangerous Krokodil to find strategies for rapid and effective determination to mitigate its adverse effects on addicts and prevent consumption. It is crucial to know the symptoms and consequences of the use of Krokodil, as well as METHODS: for identification and quantification of desomorphine, contaminants and metabolites, which can help the forensic work of diagnosis and propose actions to control and eradicate this great danger to public health around the world. Copyright © 2017 Elsevier B.V. All rights reserved.
Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report
Directory of Open Access Journals (Sweden)
Božić Ksenija
2014-01-01
Full Text Available Introduction. Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy. Case report. The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam. Conclusion. Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder.
Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety.
Moreira, Rute; Pereira, David M; Valentão, Patrícia; Andrade, Paula B
2018-06-05
Pyrrolizidine alkaloids (PA) are widely distributed in plants throughout the world, frequently in species relevant for human consumption. Apart from the toxicity that these molecules can cause in humans and livestock, PA are also known for their wide range of pharmacological properties, which can be exploited in drug discovery programs. In this work we review the current body of knowledge regarding the chemistry, toxicology, pharmacology and food safety of PA.
A Review of Pharmacologic Treatment for Compulsive Buying Disorder.
Soares, Célia; Fernandes, Natália; Morgado, Pedro
2016-04-01
At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.
Monovalent cations transfer through isolated human amnion: a new pharmacological model
Energy Technology Data Exchange (ETDEWEB)
Bara, M.; Guiet-Bara, A.; Durlach, J.
1985-04-01
Transfer of monovalent cations through the isolated human amnion consists of different factors: paracellular, coupling, ATPase dependent cellular transfer, leak cellular transfer. Understanding this transfer permits testing of the action of various substances. Physiological substances (Mg, taurine) increase ionic transfer and there is a vicarious effect between Mg and taurine. The tocolytic agents MgSO/sub 4/ and ethanol do not exhibit a good effect on the transfer: decrease with ethanol; equality between entry and exit fluxes with MgSO/sub 4/. On the other hand, amphotericin B increases mother-to-fetus transfer. Polluting metals (Pb, Cd, Hg, As) dramatically reduce exchanges and almost completely inhibit amnion permeability. Ingestion of ethanol also exhibits a dramatic effect on the exchange between mother and fetus through the amnion. Study of ionic transfer in vitro can be considered a pharmacological model to investigate the modifications of mother-fetus exchanges by various substances.
Ying, Guo; Jianping, Xie; Haiyun, Luo; Xia, Li; Jianyu, Yang; Qun, Xuan; Jianyun, Yu
2017-07-01
To determine whether students using mind maps would improve their performance in a final examination at the end of lecture-based pharmacology course. Aquasi-experimental study. Kunming Medical University, from September 2014 to January 2015. One hundred and twenty-two (122) third year undergraduate medical students, starting a 48-hour lecturebased pharmacology course, volunteered to use mind maps as one of their study strategies (intervention group), while the remaining 100 students in the class continued to use their usual study strategies (control group) over the duration of the course. The performance of both groups in the final course examination was compared. Students in the intervention group also completed a questionnaire on the usefulness of mind maps during the course and in preparation for the final examination. The students' performance of intervention group was superior to performance of the control group in all parts of a multi-modal final examination. For the multiple choice questions and comprehensive scores, average marks of 45.97 ±7.22 and 68.07 ±12.77, respectively were acquired by the control group, and 51.77 ±4.95 (pcontrol group, and were all significantly higher at 8.00 (4.00) (p=0.024), 10.00 (2.00) (pmind maps helped them to prepare more efficiently for the final exam; 90.91% believed that mind maps helped them to better understand all of pharmacology. Ninety-one percent also thought that mind maps would help them to better understand other disciplines, and 86.36% students would like the lecturers to utilize mind mapping as an alternative to conventional teaching formats, such as the use of Power Point. The addition of mind maps to students' study of pharmacology at Kunming Medical University improved their performance in all aspects of a multi-modal final examination.
Immunotropic aspect of the Bacillus coagulans probiotic action.
Bomko, Tatiana V; Nosalskaya, Tatiana N; Kabluchko, Tatiana V; Lisnyak, Yury V; Martynov, Artur V
2017-08-01
Currently, probiotics are increasingly used as the alternative to antibiotics as well as the preventive measures in humans. In particular, probiotics occupy a key position in the treatment of antibiotics-associated intestinal dysbiosis. A spore-forming microorganism lactobacillus Bacillus coagulans is one of the most promising probiotics. However, some of its pharmacological effects remain poorly understood. This study was aimed at investigation of the effect of B. coagulans (Laktovit Forte) on the intestinal dysbiosis syndrome in mice caused by streptomycin against the background of cyclophosphamide-induced cellular immunodeficiency. Pharmacological method: mouse model in vivo with immunodeficiency caused by cyclophosphamide. In mice with colitis caused by streptomycin treatment, the administration of B. coagulans (Laktovit Forte medicinal product) resulted in an antidiarrhoeal effect, normalisation of gastrointestinal motility and prevention of the animals' weight loss. Given the cyclophosphamide-induced immunosuppression and streptomycin-associated diarrhoea, the immunity was completely restored only under the action of B. coagulans. According to all parameters, B. coagulans has been proved to be more effective as compared to the Linex Forte reference product containing lacto- and bifidobacteria. © 2017 Royal Pharmaceutical Society.
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.
[Non-Pharmacological Interventions for Pregnancy-Related Sleep Disturbances].
Hung, Hsuan-Man; Chiang, Hsiao-Ching
2017-02-01
Most women experience the worse sleep quality of their life during pregnancy and the early postpartum period. Although pregnancy typically accounts for a relatively short part of a woman's life, the related sleep disturbances may have a significant and negative impact on her long-term health. Approximately 78-80% of pregnant women experience sleep disturbances, including interruptions in deep sleep, decreased total sleep time, poor subjective sleep quality, frequent night waking, and reduced sleep efficacy. Sleep disturbances during pregnancy start during the first trimester and become prevalent during the third trimester. Related factors include physiological and psychosocial changes and an unhealthy lifestyle. As non-pharmacological interventions have the potential to improve sleep quality in 70% to 80% of patients with insomnia, this is the main approached that is currently used to treat pregnancy-related sleep disturbances. Examples of these non-pharmacological interventions include music therapy, aerobic exercise, massage, progressive muscle relaxation, multi-modal interventions, and the use of a maternity support belt. The efficacy and safety of other related non-pharmacological interventions such as auricular acupressure, cognitive therapy, tai chi, and aromatherapy remain uncertain, with more empirical research required. Additionally, non-pharmacological interventions do not effectively treat sleep disturbances in all pregnant women.
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.
Developing critical understanding by teaching action research to undergraduate psychology students
Dr. Gaby Jacobs; Prof. dr. Michael Murray
2010-01-01
Action research assumes the active engagement of the stakeholders, such as the community, in the research, and a multiple level process of reflection in order to evaluate and monitor the actions taken. This makes action research a suitable methodology to increase critical understanding of the
Behavior analysis and the growth of behavioral pharmacology
Laties, Victor G.
2003-01-01
Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search ...
Directory of Open Access Journals (Sweden)
Yu. G. Levina
2014-01-01
Full Text Available The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis.
Chemotaxonomy and pharmacology of Gentianaceae
DEFF Research Database (Denmark)
Jensen, Søren Rosendal; Schripsema, Jan
2002-01-01
the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....
Cell-based therapeutic strategies for multiple sclerosis.
Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A
2017-11-01
The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.
Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina
2016-03-01
Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.
Pharmacology education in North American dental schools: the basic science survey series.
Gautam, Medha; Shaw, David H; Pate, Ted D; Lambert, H Wayne
2013-08-01
As part of the Basic Science Survey Series (BSSS) for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed course directors of basic pharmacology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-nine of sixty-seven (73.1 percent) U.S. and Canadian dental schools. The findings suggest the following: 1) substantial variation exists in instructional hours, faculty affiliation, placement within curriculum, class size, and interdisciplinary nature of pharmacology courses; 2) pharmacology course content emphasis is similar among schools; 3) the number of contact hours in pharmacology has remained stable over the past three decades; 4) recent curricular changes were often directed towards enhancing the integrative and clinically relevant aspects of pharmacology instruction; and 5) a trend toward innovative content delivery, such as use of computer-assisted instruction applications, is evident. Data, derived from this study, may be useful to pharmacology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.
Does mechanism of drug action matter to inform rational polytherapy in epilepsy?
Giussani, Giorgia; Beghi, Ettore
2013-05-01
When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.
A pharma perspective on the systems medicine and pharmacology of inflammation.
Lahoz-Beneytez, Julio; Schnizler, Katrin; Eissing, Thomas
2015-02-01
Biological systems are complex and comprehend multiple scales of organisation. Hence, holistic approaches are necessary to capture the behaviour of these entities from the molecular and cellular to the whole organism level. This also applies to the understanding and treatment of different diseases. Traditional systems biology has been successful in describing different biological phenomena at the cellular level, but it still lacks of a holistic description of the multi-scale interactions within the body. The importance of the physiological context is of particular interest in inflammation. Regulatory agencies have urged the scientific community to increase the translational power of bio-medical research and it has been recognised that modelling and simulation could be a path to follow. Interestingly, in pharma R&D, modelling and simulation has been employed since a long time ago. Systems pharmacology, and particularly physiologically based pharmacokinetic/pharmacodynamic models, serve as a suitable framework to integrate the available and emerging knowledge at different levels of the drug development process. Systems medicine and pharmacology of inflammation will potentially benefit from this framework in order to better understand inflammatory diseases and to help to transfer the vast knowledge on the molecular and cellular level into a more physiological context. Ultimately, this may lead to reliable predictions of clinical outcomes such as disease progression or treatment efficacy, contributing thereby to a better care of patients. Copyright © 2014 Elsevier Inc. All rights reserved.
Taylor, Johanna; Stubbs, Brendon; Hewitt, Catherine; Ajjan, Ramzi A.; Gilbody, Simon; Holt, Richard I. G.; Hughes, Tom; Kellar, Ian; Mahmoodi, Neda; Smith, Robert D.; Wright, Judy M.; Siddiqi, Najma
2017-01-01
People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration’s tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], pfasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design
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.
[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.
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…
Pharmacology profiling of chemicals and proteins
DEFF Research Database (Denmark)
Kringelum, Jens Vindahl
between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing....... This limitation complicates adverse effect assessment in the early drug-development phase, thus contributing to drugattrition. Prediction models offer the possibility to close these gaps and provide more complete pharmacology profiles, however improvements in performances are required for these tools to serve...... to its nonself origin, which potentially alters the pharmacology profile of the substance. The neutralization of biopharmaceuticals by antidrug antibodies (ADAs) is an important element in the immune response cascade, however studies of ADA binding site on biopharmaceuticals, referred to as B...
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.
The presence of comorbidity in Tourette syndrome increases the need for pharmacological treatment
DEFF Research Database (Denmark)
Debes, Nanette M M M; Hjalgrim, Helle; Skov, Liselotte
2009-01-01
to a better insight into the common practice in Scandinavia. Furthermore, we wanted to elaborate the influence of the presence of comorbidities and of the severity of tics on pharmacological treatment. We have examined the frequency, art, and reason for pharmacological treatment in a Danish clinical cohort...... of 314 children with Tourette syndrome. In total, 60.5% of the children once had received pharmacological treatment. Mostly, the treatment was started because of tics or ADHD. If ADHD or obsessive-compulsive disorder were present, more children received pharmacological treatment and more different agents...... were tried. The children who received pharmacological treatment had more severe tics than those without medication....
Anti-inflammatory actions of acupuncture
Directory of Open Access Journals (Sweden)
Freek J. Zijlstra
2003-01-01
Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.
Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.
Russo, Ethan B; Marcu, Jahan
2017-01-01
The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed "pharmacological treasure trove." © 2017 Elsevier Inc. All rights reserved.
Medicinal, Pharmacological and Phytochemical Potentials of ...
African Journals Online (AJOL)
Medicinal, Pharmacological and Phytochemical Potentials of Annona Comosus linn. ... Therapeutic plants, and the drugs derived from them, are the most important ... also as treatment to: diarrhea, indigestion, pneumonia, bronchitis, arthritis, ...
Directory of Open Access Journals (Sweden)
Jovičić Jelena
2016-01-01
Full Text Available Introduction: Pain is a highly subjective experience and different studies have shown that the perception of the pain intensity depends on multiple factors, such as: gender, race, age, eye or hair color, socio-economic status, education, as well as psychological status of the person, etc. Despite those determinants there is an discrepancy in pain treating approach between the USA and the European countries. Low back pain has become a major socio-economic problem in the USA, with 70-85% of people in the North America being affected throughout their lifes compared with the average prevalence of back pain In Western Europe as 15%. Overall, NSAIDs are the most commonly prescribed medication for low back pain worldwide, however with liberalization of the law in the USA within past 20 years, and with the promotion of opioids as highly effective and safe treatment, they are getting prescribed widely and readily for different chronic pain conditions including chronic low back pain. Low back pain has become a major socio-economic problem in the USA, and Western Europe. The purpose of this prospective study was to determine the utilization of pharmacological and non-pharmacological treatments for chronic low back pain in developing countries. Methods: After approval of the ethics committee Medical School University of Belgrade we enrolled 185 patients. Any patients who were > 18 years, diagnosed with chronic low back pain and did not have a history of malignancy are included in the study. All of them completed the study. Results: Patients were between 21 and 91 years old (average age 61.2 ± 14.7, 43.5% of them were males and 56.5% females. The pain duration for these patients ranged from 2 months up to 20 years. Average VAS pain scores in rest 4.7 ± 2.3 and in movement 5.2 ± 2.1. All of these patients exploited different types of non-pharmacological treatments for their painful condition. The average improvements after these treatments were: physical
Status of Undergraduate Pharmacology Laboratories in Colleges of Pharmacy in the United States
Katz, Norman L.; And Others
1978-01-01
U.S. colleges of pharmacy were surveyed in 1976 to determine whether a trend exists in continuing, discontinuing, or restructuring laboratory time in pharmaceutical education. Data regarding core undergraduate pharmacology courses, undergraduate pharmacology laboratory status, and pharmacology faculty are presented. (LBH)
An Endocrine Pharmacology Course for the Clinically-Oriented Pharmacy Curriculum
Rahwan, Ralf G.
1976-01-01
In view of trends in clinical pharmacy education, the role of the traditional basic sciences has to be reassessed. An endocrine pharmacology course comprised of 49 clock-hours and open for professional undergraduate and graduate credit is described that blends basic and applied pharmacology. (LBH)
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.
GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects
DEFF Research Database (Denmark)
Krogsgaard-Larsen, P; Frølund, B; Frydenvang, Karla Andrea
2000-01-01
demonstrated that neuronal and glial GABA transport mechanisms have dissimilar substrate specificities. With GABA transport mechanisms as pharmacological targets, strategies for pharmacological interventions with the purpose of stimulating GABA neurotransmission seem to be (1) effective blockade of neuronal......, tiagabine (49) containing (R)-nipecotic acid (24) as the GABA transport carrier-recognizing structure element, is now marketed as an antiepileptic agent....
Pharmacological treatment of sexual offenders in German outpatient treatment centers.
Turner, Daniel; Gregório Hertz, Priscilla; Sauter, Julia; Briken, Peer; Rettenberger, Martin
2018-05-04
In Germany, depending on a sexual offender's culpability and the severity of the offence, he/she can be placed either in the forensic-psychiatric or the correctional system. Numbers related to the pharmacological treatment of sexual offenders for the correctional system are missing so far. In sexual offenders, the pharmacological treatment of paraphilic disorders is of special importance. The present study aimed at assessing the prevalence of pharmacological sexual offender treatment in German outpatient treatment centers supervising mainly clients from the correctional sector. An online questionnaire was sent to 112 outpatient treatment centers and 21 provided data relevant for the present study. The included institutions reported about a total of 813 sexual offenders, of whom 200 (24.6%) were treated with pharmacological agents, most frequently antipsychotics (14.8%) and selective-serotonin-reuptake-inhibitors (7.1%). Of the total sample, 26.7% of sexual offenders were diagnosed with a paraphilic - mainly with a pedophilic - disorder. Only 2% were treated with androgen-deprivation therapy. Compared with forensic-psychiatric institutions, only a minority of sexual offenders are treated with medication specifically addressing paraphilic symptomatology. However, the prevalence of paraphilic disorders found in the present study suggests that pharmacological treatment of paraphilic fantasies and behaviors could be of great importance in the correctional sector as well.
The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.
White, C Michael
2017-03-01
This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events. © 2016, The American College of Clinical Pharmacology.
Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.
Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph
2017-01-01
Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and
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,…
Phytochemistry, pharmacology, and clinical trials of Morus alba.
Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin
2016-01-01
The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
Pharmaceutical and pharmacological approaches for bioavailability
Indian Academy of Sciences (India)
2014-01-27
Jan 27, 2014 ... Etoposide posses high plasma protein binding (97%) and is degraded via ... The present article gives insight on pharmaceutical and pharmacological .... caprolactone and were found efficient as drug delivery vehicles.
Gene specific actions of thyroid hormone receptor subtypes.
Directory of Open Access Journals (Sweden)
Jean Z Lin
Full Text Available There are two homologous thyroid hormone (TH receptors (TRs α and β, which are members of the nuclear hormone receptor (NR family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/- T(3 in two cell backgrounds (HepG2 and HeLa. We find that hundreds of genes respond to T(3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T(3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/- T(3, TR regulation patterns and T(3 dose response. Cycloheximide (CHX treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs.
Directory of Open Access Journals (Sweden)
Hafiz Muhammad Asif
2014-07-01
Full Text Available Trachyspermum ammi Linn. (T. ammi is an aromatic, grassy, annual plant belonging to Umbelliferae family which grows in the east of India, Pakistan, Iran, and Egypt. T. ammi has been used traditionally to treat arthritis, colic, diarrhea and gastrointestinal problems. In addition to these medicinal uses, T. ammi continues to be valued around the world as an important cooking spice and is believed to relief the common cold, flu-like symptoms, headaches, and even painful menstrual periods. These multiple uses can be explained by its several active compounds. The phytochemical studies on T. ammi seeds have revealed the presence of alkaloids, steroids, fixed oils, glycosides, tannins, saponin and flavonoids, cumene, thymene, amino acids and dietary fiber essential oils like thymol, c-terpinene, p-cymene. Several pharmacological studies on anti-tussive effect, inhibitory effect on histamine (H1 receptors, antihypertensive, antispasmodic, bronchodilator, hepato-protective, analgesic, anti-inflammatory, antioxidant and anti mutagenic activities of T. ammi seed extracts have been reported in the literature. The present review is therefore, an effort to give a detailed survey of the literature on traditional, phytochemical and pharmacological properties of T. ammi.
Pharmacological activity of salvinorin A, the major component of Salvia divinorum.
Listos, Joanna; Merska, Alicja; Fidecka, Sylwia
2011-01-01
The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.
Stress Effects on Multiple Memory System Interactions
Ness, Deborah; Calabrese, Pasquale
2016-01-01
Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour. PMID:27034845
Stress Effects on Multiple Memory System Interactions.
Ness, Deborah; Calabrese, Pasquale
2016-01-01
Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.
Stress Effects on Multiple Memory System Interactions
Directory of Open Access Journals (Sweden)
Deborah Ness
2016-01-01
Full Text Available Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.
Ethnobotanical, phytochemical and pharmacological properties of ...
African Journals Online (AJOL)
Electronic search engines such as Google, Google scholar, publishing sites such as Elsevier .... A number of pharmacological activities of C. bulbispermum have been ..... bulbispermum using the direct plate method and minimum inhibitory ...
Pharmacological and non- pharmacological treatment of hypertension: A review article
Directory of Open Access Journals (Sweden)
Marjan Seyedmazhari
2013-01-01
Full Text Available BACKGROUND: Hypertension is a worldwide epidemic disease. It is more common and more severe in elderly persons. Various studies however have estimated 41.9 million men and 27.8 million women to have prehypertension. Diagnosis and early treatment of prehypertension are of utmost importance. Although hypertension is usually divided into 2 general categories of essential (primary and secondary hypertension, the initial treatment for hypertension often depends on its stage which is determined by systolic and diastolic blood pressure. Lifestyle modification is the first step in treating stage one hypertension. Pharmaceutical treatments including diuretics, angiotensin converting enzyme (ACE inhibitors, calcium blockers, beta blockers, and angiotensin receptor blockers will be recommended if lifestyle modification fails to control blood pressure. METHODS: The PubMed database was searched by a number of keywords including hypertension, pharmaceutical treatment, and non-pharmaceutical treatment. The results were limited by determining a date range of 2008-11. RESULTS: High blood pressure causes major health problems for many people around the world. It should be controlled because of its high mortality and morbidity. However, in order to select an appropriate treatment modality, it is initially important to diagnose the kinds and stages of hypertension. Pharmaceutical or non-pharmaceutical treatments can then be employed to control this serious disease. CONCLUSION: Treating hypertension depends on the kinds and stages of this disease. Several tips should be considered when selecting a method of treatment. Keywords: Hypertension, Pharmacological treatment, Non-pharmacological treatment
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.
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Keppel Hesselink JM
2013-08-01
Full Text Available Jan M Keppel Hesselink Department of Pharmacology, University of Witten/Herdecke, Witten, Germany Abstract: The history of development of new concepts in pharmacology is a highly interesting topic. This review discusses scientific insights related to palmitoylethanolamide (PEA and its progression over a period of six decades, especially in light of the work of the science sociologists, Ludwig Fleck and Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome proliferator-activated receptors was the beginning of a completely new understanding of many important homeostatic physiologic mechanisms in the human body. These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient known already for more than 50 years. PEA is synthesized and metabolized in animal cells via a number of enzymes and has a multitude of physiologic functions related to metabolic homeostasis. PEA was identified in the 1950s as a therapeutic principle with potent anti-inflammatory properties. Since 1975, its analgesic properties have been noted and explored in a variety of chronic pain states. Since 2008, PEA has been available as a nutraceutical under the brand names Normast® and PeaPure®. A literature search on PEA meanwhile has yielded over 350 papers, all referenced in PubMed, describing the physiologic properties of this endogenous modulator and its pharmacologic and therapeutic profile. This review describes the emergence of concepts related to the pharmacologic profile of PEA, with an emphasis on the search into its mechanism of action and the impact of failing to identify such mechanism in the period 1957–1993, on the acceptance of PEA as an anti-inflammatory and analgesic compound. Keywords: palmitoylethanolamide, sociology, science, paradigm, peroxisome proliferator-activated receptor-alpha, nutraceutical
Li, Ke; Li, Junfang; Su, Jin; Xiao, Xuefeng; Peng, Xiujuan; Liu, Feng; Li, Defeng; Zhang, Yi; Chong, Tao; Xu, Haiyu; Liu, Changxiao; Yang, Hongjun
2018-03-07
The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic
Pharmacological properties of Salvia officinalis and its components
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Ahmad Ghorbani
2017-10-01
Full Text Available Salvia officinalis (Sage is a plant in the family of Labiatae/Lamiaceae. It is native to Middle East and Mediterranean areas, but today has been naturalized throughout the world. In folk medicine, S. officinalis has been used for the treatment of different kinds of disorders including seizure, ulcers, gout, rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and hyperglycemia. In recent years, this plant has been a subject of intensive studies to document its traditional use and to find new biological effects. These studies have revealed a wide range of pharmacological activities for S. officinalis. Present review highlights the up-to-date information on the pharmacological findings that have been frequently reported for S. officinalis. These findings include anticancer, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects. Also, chemical constituents responsible for pharmacological effects of S. officinalis and the clinical studies on this plant are presented and discussed.
Acanthopanax senticosus: review of botany, chemistry and pharmacology.
Huang, Linzhang; Zhao, Hongfang; Huang, Baokang; Zheng, Chengjian; Peng, Wei; Qin, Luping
2011-02-01
Acanthopanax senticosus (Rupr. et Maxim) Harms (Araliaceae), also called Siberian Ginseng, Eleutherococcus senticosus, and Ciwujia in Chinese, is a widely used traditional Chinese herb that could invigorate qi, strengthen the spleen, and nourish kidney in the theory of Traditional Chinese Medicine. With high medicinal value, Acanthopanax senticosus (AS, thereafter) is popularly used as an "adaptogen" like Panax ginseng. In recent decades, a great number of chemical, pharmacological, and clinical studies on AS have been carried out worldwide. Several kinds of chemical compounds have been reported, including triterpenoid saponins, lignans, coumarins, and flavones, among which, phenolic compounds such as syringin and eleutheroside E, were considered to be the most active components. Considerable pharmacological experiments both in vitro and in vivo have persuasively demonstrated that AS possessed anti-stress, antiulcer, anti-irradiation, anticancer, anti-inflammatory and hepatoprotective activities, etc. The present review is an up-to-date and comprehensive analysis of the botany, chemistry, pharmacology, toxicity and clinical trials of AS.
DEFF Research Database (Denmark)
Kopec, Wojciech; Khandelia, Himanshu
2014-01-01
Thioridazine is a well-known dopamine-antagonist drug with a wide range of pharmacological properties ranging from neuroleptic to antimicrobial and even anticancer activity. Thioridazine is a critical component of a promising multi-drug therapy against M. tuberculosis. Amongst the various propose......-membrane interactions, and reinforce the wider, emerging view of action of many small, bioactive compounds....... mechanisms of action, the cell membrane-mediated one is peculiarly tempting due to the distinctive feature of phenothiazine drug family to accumulate in selected body tissues. In this study, we employ long-scale molecular dynamics simulations to investigate the interactions of three different concentrations...
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Rubneide Barreto Silva Gallo
2018-01-01
Trial registration: NCT01389128. [Gallo RBS, Santana LS, Marcolin AC, Duarte G, Quintana SM (2018 Sequential application of non-pharmacological interventions reduces the severity of labour pain, delays use of pharmacological analgesia, and improves some obstetric outcomes: a randomised trial. Journal of Physiotherapy 64: 33–40
Albers, D S; Sonsalla, P K
1995-12-01
Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate
Common mullein, pharmacological and chemical aspects
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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.
Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology.
Yang, Fude; Dong, Xiaoxv; Yin, Xingbin; Wang, Wenping; You, Longtai; Ni, Jian
2017-01-01
Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b 2 , c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri . This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.
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…
Myocardial perfusion scintigraphy with exercise and pharmacological stress
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Sundram, F X [General Hospital of Singapore, Dept. of Nuclear Medicine (Senegal)
1996-12-31
Cardiac studies including myocardial perfusion scintigraphy was begun in the Singapore General Hospital, nuclear medicine department in 1983. From a few patients per year using planar imaging, we have in 1994 studied 1500 patients for myocardial perfusion, using mainly SPECT (single-photon emission computerised tomography) and radionuclides such as Thallium-201, Technetium-99m sestamibi and Tc-99m tetrofosmin. Patients have been stressed using treadmill exercise or pharmacological agents; we have used dipyridamole, and dobutamine for pharmacological stress but have no experience with intravenous adenosine.
Myocardial perfusion scintigraphy with exercise and pharmacological stress
International Nuclear Information System (INIS)
Sundram, F.X.
1995-01-01
Cardiac studies including myocardial perfusion scintigraphy was begun in the Singapore General Hospital, nuclear medicine department in 1983. From a few patients per year using planar imaging, we have in 1994 studied 1500 patients for myocardial perfusion, using mainly SPECT (single-photon emission computerised tomography) and radionuclides such as Thallium-201, Technetium-99m sestamibi and Tc-99m tetrofosmin. Patients have been stressed using treadmill exercise or pharmacological agents; we have used dipyridamole, and dobutamine for pharmacological stress but have no experience with intravenous adenosine
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André Russowsky Brunoni
Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention
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.
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Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio [UEPG, Universidade Estadual de Ponta Grossa, Departamento de Analises Clinicas eToxicologicas, Ponta Grossa, PR (Brazil); Khalil, Omar Arafat Kdudsi [IFG, Instituto Federal de Goias, Campus de Formosa, Formosa - GO (Brazil); Carvalho, Claudio Teodoro de [UFGD, Universidade Federal da Grande Dourados, Faculdade de Ciencias Exatas e Tecnologias, Dourados-MS (Brazil); Bannach, Gilbert [UNESP, Universidade Estadual Paulista Julio de Mesquita Filho, Faculdade de Ciencias de Bauru, Bauru, SP (Brazil)
2011-07-01
Free radicals are highly reactive species generated in living organisms for the purpose of protection. However, in some circumstances, they are responsible for the occurrence or aggravation of tissue damage. Many anti-inflammatory drugs have a direct effect on free radicals and not radical reactive species, which contributes to its actions against inflammation. Ketoprofen is a nonsteroidal anti-inflammatory agent that generates free radicals by photo irradiation and has an important hemolytic effect with that. The complexation of metals to different drugs has been used as a strategy to improve the pharmacological action of different molecules and reduce their side effects. This paper presents the results of ketoprofen and their metallic complexes action on erythrocytes and free radicals. It was observed that the cerium enhances the scavenger properties of ketoprofen on free radicals, while copper enhances its action over non-radical oxidants. Copper also reduced the hemolytic effect presented by ketoprofen meanwhile its cerium derivative maintained it. (author)
Temporal trends in pharmacology publications by pharmacy institutes: A deeper dig.
Bhatt, Parloop Amit; Patel, Zarana
2016-10-01
Publications in Indian Journal of Pharmacology (IJP) are the face of contemporary pharmacology practices followed in health-care profession - a knowledge-based profession. It depicts trends in terms of quantity (proportions), quality, type (preclinical/clinical), thrust areas, etc., of pharmacology followed by biomedical community professions both nationally and internationally. This article aims to establish temporal trends in pharmacology research by pharmacy institutes in light of its publications to IJP from 2010 to 2015. The website of IJP was searched for publications year and issue wise for contributing authors from pharmacy institutions and analyzed for types of publications, their source and the categories of research documented in these publications. A total of 1034 articles were published, of which 189 (18%) articles were published by pharmacy institutes, of which 90% ( n = 170) were contributed from pharmacy institutes within India whereas 10% ( n = 19) from international pharmacy institutes. 75% of these were research publication, the majority of which (65%) were related to preclinical screening of phytochemical constituents from plants. With multi and interdisciplinary collaborations in pharmacy profession the trend needs to improve toward molecular and cellular pharmacology and clinical studies.
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.
Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan
2018-04-01
The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides(Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.
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
Daien, Claire Immediato; Hua, Charlotte; Combe, Bernard; Landewe, Robert
2017-01-01
To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). The expert committee defined research questions concerning
Internet discussion forums as part of a student-centred teaching concept of pharmacology.
Sucha, Michael; Engelhardt, Stefan; Sarikas, Antonio
2013-01-01
The world wide web opens up new opportunities to interconnect electronic and classroom teaching and to promote active student participation. In this project article we describe the use of internet discussion forums as part of a student-centred teaching concept of pharmacology and discuss its advantages and disadvantages based on evaluation data and current literature. Final year medical students at the Technische Universität München (Munich, Germany) with the elective pharmacology moderated an internet forum that allowed all students to discuss pharmacology-related questions. Evaluation results of forum participants and elective students demonstrated a learning benefit of internet forums in pharmacology teaching. Internet discussion forums offer an easy-to-implement and effective way to actively engage students and increase the learning benefit of electronic and classroom teaching in pharmacology.
Development of responder criteria for multicomponent non-pharmacological treatment in fibromyalgia
Vervoort, V.M.; Vriezekolk, J.E.; Ende, C.H.M. van den
2017-01-01
OBJECTIVES: There is a need to identify individual treatment success in patients with fibromyalgia (FM) who received non-pharmacological treatment. The present study described responder criteria for multicomponent non-pharmacological treatment in FM, and estimated and compared their sensitivity and
Molecular Mechanism for Various Pharmacological Activities of NSAIDS
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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.
The Role of Pharmacology in Ureteral Physiology and Expulsive Therapy
Jerde, Travis J.; Nakada, Stephen Y.
2007-04-01
Research in the field of ureteral physiology and pharmacology has traditionally been directed toward relaxation of ureteral spasm as a mechanism of analgesia during painful ureteral obstruction, most often stone-induced episodes. However, interest in this field has expanded greatly in recent years with the expanded use of alpha-blocker therapy for inducing stone passage, a usage now termed "medical expulsive therapy". While most clinical reports involving expulsive therapy have focused on alpha receptor or calcium channel blockade, there are diverse studies investigating pharmacological ureteral relaxation with novel agents including cyclooxygenase inhibitors, small molecule beta receptor agonists, neurokinin antagonists, and phosphodiesterase inhibitors. In addition, cutting edge molecular biology research is revealing promising potential therapeutic targets aimed at specific molecular changes that occur during the acute obstruction that accompanies stone disease. The purpose of this report is to review the use of pharmacological agents as ureteral smooth muscle relaxants clinically, and to look into the future of expulsive therapy by reviewing the available literature of ureteral physiology and pharmacology research.
[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.
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
Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E
2015-01-01
To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.
Miscellaneous Lasing Actions in Organo-Lead Halide Perovskite Films.
Duan, Zonghui; Wang, Shuai; Yi, Ningbo; Gu, Zhiyuan; Gao, Yisheng; Song, Qinghai; Xiao, Shumin
2017-06-21
Lasing actions in organo-lead halide perovskite films have been heavily studied in the past few years. However, due to the disordered nature of synthesized perovskite films, the lasing actions are usually understood as random lasers that are formed by multiple scattering. Herein, we demonstrate the miscellaneous lasing actions in organo-lead halide perovskite films. In addition to the random lasers, we show that a single or a few perovskite microparticles can generate laser emissions with their internal resonances instead of multiple scattering among them. We experimentally observed and numerically confirmed whispering gallery (WG)-like microlasers in polygon shaped and other deformed microparticles. Meanwhile, owing to the nature of total internal reflection and the novel shape of the nanoparticle, the size of the perovskite WG laser can be significantly decreased to a few hundred nanometers. Thus, wavelength-scale lead halide perovskite lasers were realized for the first time. All of these laser behaviors are complementary to typical random lasers in perovskite film and will help the understanding of lasing actions in complex lead halide perovskite systems.
Keijsers, Carolina J P W; Brouwers, Jacobus R B J; de Wildt, Dick J; Custers, Eugene J F M; Ten Cate, Olle Th J; Hazen, Ankie C M; Jansen, Paul A F
2014-10-01
Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical students after their undergraduate training. Differences could serve as a starting point from which to develop joint interdisciplinary educational programmes for better prescribing. In a cross-sectional design, the knowledge and skills of advanced pharmacy and medical students were assessed, using a standardized test with three domains (basic pharmacology knowledge, clinical or applied pharmacology knowledge and pharmacotherapy skills) and eight subdomains (pharmacodynamics, pharmacokinetics, interactions and side-effects, Anatomical Therapeutic Chemical Classification groups, prescribing, prescribing for special groups, drug information, regulations and laws, prescription writing). Four hundred and fifty-one medical and 151 pharmacy students were included between August 2010 and July 2012. The response rate was 81%. Pharmacy students had better knowledge of basic pharmacology than medical students (77.0% vs. 68.2% correct answers; P students had better skills than pharmacy students in writing prescriptions (68.6% vs. 50.7%; P students had similar knowledge of applied pharmacology (73.8% vs. 72.2%, P = 0.124, δ = 0.15). Pharmacy students have better knowledge of basic pharmacology, but not of the application of pharmacology knowledge, than medical students, whereas medical students are better at writing prescriptions. Professional differences in knowledge and skills therefore might well stem from their undergraduate education. Knowledge of these differences could be harnessed to develop a joint interdisciplinary education for both students and professionals. © 2014 The British Pharmacological Society.
Energy Technology Data Exchange (ETDEWEB)
Oliveira, Karina Corleto
2014-07-01
The serum production in Brazil, the only effective treatment in cases of snakebites, uses horses that although large size, have reduced l lifespan compared with horses not immunized. Ionizing radiation has been shown as an excellent tool in reducing the toxicity of venoms and toxins isolated, and promote the achievement of better immunogens for serum production, and contributing to the welfare of serum-producing animals. It is known, however, that the effects of ionizing radiation on protein are characterized by various chemical modifications, such as fragmentation, cross-linking due to aggregation and oxidation products generated by water radiolysis. However, the action of gamma radiation on toxins is not yet fully understood structurally and pharmacologically, a fact that prevents the application of this methodology in the serum production process. So we proposed in this paper the characterization of crotamine, an important protein from the venom of Crotalus durissus terrificus species, irradiated with {sup 60}Co gamma rays. After isolating the toxin by chromatographic techniques and testing to prove the obtaining of pure crotamine, it was irradiated with gamma rays and subjected to structural analysis, Fluorescence and Circular Dichroism. Using high hydrostatic pressure tests were also conducted in order to verify that the conformational changes caused by radiation suffer modifications under high pressures. From the pharmacological point of view, muscle contraction tests were conducted with the objective of limiting the action of crotamine in smooth muscle as well as the change in the action of toxin caused structural changes to the front. Analysis of Circular Dichroism and Fluorescence showed changes in structural conformation of crotamine when subjected to gamma radiation and that such changes possibly occurring in the secondary and tertiary structure of the protein. The observed in pharmacological tests showed that the irradiated crotamine was less effective
Li, Shuping; Cheng, Xuemei; Wang, Changhong
2017-05-05
The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research. Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS's dissertations. The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory. Based on this review, there is some evidence for extracts' pharmacological effects on Alzheimer's and Parkinson's diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding
Automated tool for virtual screening and pharmacology-based pathway prediction and analysis
Directory of Open Access Journals (Sweden)
Sugandh Kumar
2017-10-01
Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.
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
Verma, Vandana; Tripathi, Avinash C; Saraf, Shailendra K
2016-11-01
In folk medicine, the stem bark of Streblus asper Lour. (Moraceae) has been reported to possess anticonvulsant activity. However, no systematic/scientific validation is available. Objective This study explores the constituents in the stem bark, their biosassy-guided isolation and their efficacy in neuro-pharmacological disorders, for validating the traditional claims. Microwave-assisted extraction (MAE) technique was employed to obtain the crude extract. The n-hexane, dichloromethane and aqueous fractions were prepared and phytoconstituents were ascertained by phytochemical tests. The isolated compound, betulin, was characterized by different physicochemical and spectral methods, including HPTLC. Finally, neuro-pharmacological evaluations were conducted at 100, 200, 400 mg/kg b.w., p.o. (25, 50, 100 mg/kg b.w. for betulin) doses in BALB/c mice. The n-hexane fraction (400 mg/kg), and isolated compound betulin (100 mg/kg), showed maximum anticonvulsant activity in maximal electroshock (87.84% and 85.14% seizure inhibition), and isoniazid induced convulsion models (88.85% and 83.18% seizure inhibition), respectively. A dose-dependent attenuation of epileptic seizures was observed, probably through GABArgic mechanism of anticonvulsant action. Moreover, the antidepressant study was also conducted using behavioural models and the results expound that n-hexane and dichloromethane fractions (400 mg/kg) significantly reduced the duration of immobility, as compared to the control. This study reports some novel aspects like applying an environmentally benign/green approach of MAE, neuro-pharmacological screening and use of docking studies, for the first time, on the plant S. asper. The findings present a rational explanation for its use in traditional medicine, for the management of neuro-pharmacological disorders.
Patients and ICU nurses' perspectives of non-pharmacological interventions for pain management.
Gélinas, Céline; Arbour, Caroline; Michaud, Cécile; Robar, Lauren; Côté, José
2013-11-01
Pain is a major stressor for critically ill patients. To maximize pain relief, non-pharmacological interventions are an interesting avenue to explore. The study aim was to describe the perspectives of patients/family members and nurses about the usefulness, relevance and feasibility of non-pharmacological interventions for pain management in the intensive care unit (ICU). A qualitative descriptive design was used. Patients/family members (n = 6) with a previous experience of ICU hospitalization and ICU nurses (n = 32) were recruited. Using a semi-structured discussion guide, participants were asked to share their perspective about non-pharmacological interventions that they found useful, relevant and feasible for pain management in the ICU. Interventions were clustered into five categories: a) cognitive-behavioural, b) physical, c) emotional support, d) helping with activities of daily living and, e) creating a comfortable environment. A total of eight focus groups (FGs) with patients/family members (two FGs) and ICU nurses (six FGs) were conducted. Overall, 33 non-pharmacological interventions were discussed. The top four non-pharmacological interventions found to be useful, relevant and feasible in at least half of the FGs were music therapy and distraction (cognitive-behavioural category), simple massage (physical category) and family presence facilitation (emotional support category). Interestingly, patients/family members and nurses showed different interests towards some interventions. For instance, patients discussed more about active listening/reality orientation, while nurses talked mostly about teaching/positioning. Four non-pharmacological interventions reached consensus in patients and nurses' FGs to be useful, relevant and feasible for pain management in the ICU. Other interventions seemed to be influenced by personal experience or professional role of the participants. While more evidence is required to conclude to their effectiveness, ICU nurses can
Correlation of pharmacological activity and receptor binding of guanabenz during development
International Nuclear Information System (INIS)
Zoltoski, R.K.
1989-01-01
Many studies to elucidate the pharmacokinetic, pharmacodynamic, and molecular pharmacological profile of guanabenz, an α 2 -adrenergic receptor agonist, have been reported; however, the effects of this drug on the developing fetus have been largely ignored. The ability of a drug to alter fetal cardiovascular activity is dependent upon both the penetration of the drug across the placenta and upon maturation of the system(s) through which the drug exerts its effects. Consequently, it is hypothesized that the pharmacological activity of guanabenz on the fetus is influenced both by placenta actions on drug transfer and the time course of development of the central and/or peripheral α 2 adrenergic receptor system(s) through which the drug exerts its effects. Guanabenz (GB) when administered to the maternal sheep elicited a cardiovascular response similar to that observed in rats, dogs, and humans. An initial, transient increase in mean arterial pressure (MAP) was followed by a sustained decrease in MAP. This decrease in MAP was accompanied by a prolonged decrease in heart rate (HR). No cardiovascular response to maternally administered GB was observed in the fetal lamb. Pharmacokinetic studies revealed that GB is widely distributed in the pregnant ewe; however, the placenta appears to act as a relative barrier to the transfer of GB into the fetal compartment. In order to ascertain if the mature fetal lamb had developed functional α 2 -adrenergic receptors, GB was administered directly to the fetus. A transient increase in MAP was elicited; however, no prolonged decrease in either MAP or HR occurred. Following validation of [ 3 H]guanabenz ([ 3 H]GB) binding assay in rat cerebral cortex, studies to correlate [ 3 H]GB binding in sheep cortex with pharmacodynamic response was conducted
Four-year follow-up study of pharmacological treatment in pathological gamblers.
Rosenberg, Oded; Dinur, Limor Klein; Dannon, Pinhas N
2013-01-01
In the past decade, we have witnessed the emergence of pharmacological treatments for pathological gambling with some success but many question marks. We aimed to explore pharmacological treatments that have been previously explored with some success, with the intent of comparing their efficacy and pave the way to larger placebo-controlled trials. In this study, we allocated 78 patients to 4 different types of psychotropic medications: naltrexone, topiramate, bupropion, and escitalopram. We treated patients for more than 2 years, with additional 2-year follow-ups without medication. The sample was evaluated using the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Global Assessment of Functioning, and the Visual Analog Scale to measure general well-being before enrollment as well as at 1 month, 6 months, 24 months, and 48 months after beginning medication treatment. During the first 2 years of treatment, 34 patients dropped out, with one more dropping out during the additional 2 years of follow-up. Significant improvement on all rating scales was seen in all groups after 2 years, except HAMD in the group that received topiramate. We found the naltrexone-treated group of patients to have a statistically significant lower dropout rate compared with other groups, statistically significant lower HAMD scores in comparison to the group treated with bupropion, statistically significant lower Hamilton Anxiety Rating Scale score compared to the groups treated with escitalopram and topiramate, and significantly higher Visual Analog Scale scores compared to the groups treated with bupropion and topiramate. Pathological gambling is essentially a biopsychological disorder that may be attenuated provided that patients adhere to medication. In our study, among 4 medications with different mechanisms of action, naltrexone was found to be the most effective. Placebo-controlled studies involving large numbers of subjects are required before
Lahiri, Sharon W
2017-12-01
IN BRIEF Caring for people with type 2 diabetes requires a patient-centered approach to treatment targets and medication regimens. Focusing on patients' individual characteristics, needs, and treatment responses can improve compliance and clinical outcomes. Medication selection can be guided by the mechanisms of action, advantages, disadvantages, and costs of available options; patients' behavioral and psychological variables, personal preferences, and socioeconomic status also should be taken into account. This article provides an overview of patient-centered and individualized diabetes management, offers pharmacological recommendations for specific clinical scenarios, and describes a complicated case illustrating the patient-centered approach in clinical practice.
Quality of reporting statistics in two Indian pharmacology journals.
Jaykaran; Yadav, Preeti
2011-04-01
To evaluate the reporting of the statistical methods in articles published in two Indian pharmacology journals. 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 reporting of method of description and central tendencies. Inferential statistics was evaluated on the basis of fulfilling of assumption of statistical methods and appropriateness of statistical tests. Values are described as frequencies, percentage, and 95% confidence interval (CI) around the percentages. Inappropriate descriptive statistics was observed in 150 (78.1%, 95% CI 71.7-83.3%) articles. Most common reason for this inappropriate descriptive statistics was use of mean ± SEM at the place of "mean (SD)" or "mean ± SD." Most common statistical method used was one-way ANOVA (58.4%). Information regarding checking of assumption of statistical test was mentioned in only two articles. Inappropriate statistical test was observed in 61 (31.7%, 95% CI 25.6-38.6%) articles. Most common reason for inappropriate statistical test was the use of two group test for three or more groups. Articles published in two Indian pharmacology journals are not devoid of statistical errors.
Taylor, Johanna; Stubbs, Brendon; Hewitt, Catherine; Ajjan, Ramzi A.; Alderson, Sarah L.; Gilbody, Simon; Holt, Richard I. G.; Hosali, Prakash; Hughes, Tom; Kayalackakom, Tarron; Kellar, Ian; Lewis, Helen; Mahmoodi, Neda; McDermid, Kirstine; Smith, Robert D.
2017-01-01
People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs...
Corn Silk (Stigma Maydis in Healthcare: A Phytochemical and Pharmacological Review
Directory of Open Access Journals (Sweden)
Shuhaimi Mustafa
2012-08-01
Full Text Available Corn silk (Stigma maydis is an important herb used traditionally by the Chinese, and Native Americans to treat many diseases. It is also used as traditional medicine in many parts of the world such as Turkey, United States and France. Its potential antioxidant and healthcare applications as diuretic agent, in hyperglycemia reduction, as anti-depressant and anti-fatigue use have been claimed in several reports. Other uses of corn silk include teas and supplements to treat urinary related problems. The potential use is very much related to its properties and mechanism of action of its plant’s bioactive constituents such as flavonoids and terpenoids. As such, this review will cover the research findings on the potential applications of corn silk in healthcare which include its phytochemical and pharmacological activities. In addition, the botanical description and its toxicological studies are also included.
Alternative pharmacological treatment options for agitation in Alzheimer’s disease
Directory of Open Access Journals (Sweden)
Francesco Panza
2015-11-01
Full Text Available In patients with dementia and Alzheimer’s disease (AD, treatment of neuropsychiatric symptoms (NPS is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs, with disappointing results. However, evidence coming from recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/ quinidine, cannabinoids, and citalopram showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia.
Pharmacological screening of Malian medicinal plants used against epilepsy and convulsions
DEFF Research Database (Denmark)
Pedersen, Mikael E; Vestergaard, Henrik T; Hansen, Suzanne L
2009-01-01
Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants.......Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants....
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…
Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management.
Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De
2012-09-01
Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.
Directory of Open Access Journals (Sweden)
Kojo Agyemang
2013-01-01
Full Text Available The disease burden of diabetes mellitus is increasing throughout the world. The need for more potent drugs to complement the present anti-diabetic drugs has become an imperative. Astragalus membranaceus, a key component of most Chinese herbal anti-diabetic formulas, has been an important prospect for lead anti-diabetic compounds. It has been progressively studied for its anti-diabetic properties. Ethnopharmacological studies have established its potential to alleviate diabetes mellitus. Recent studies have sought to relate its chemical constituents to types 1 and 2 diabetes mellitus. Its total polysaccharides, saponins, and flavonoids fractions and several isolated compounds have been the most studied. The total polysaccharides fraction demonstrated activity to both types 1 and 2 diabetes mellitus. This paper discusses the anti-diabetic effects and pharmacological action of the chemical constituents in relation to types 1 and 2 diabetes mellitus.
Strains of Rodents and the Pharmacology of Learning and Memory
Ammassari-Teule, Martine; Castellano, Claudio
2004-01-01
Mendelian genetic tools have extensively been used to improve the description of the pharmacological mechanisms involved in learning and memory. The first part of this short review describes experiments involving the bidirectional selection of rats or mice for extreme behavioral characteristics or for sensitivity to pharmacological treatments. The second part focuses specifically on inbreeding. In conclusion, the advantages and the limits of a Mendelian pharmacog...
Double pharmacological challenge on repolarization opens new avenues for drug safety research
DEFF Research Database (Denmark)
Thomsen, Morten Bækgaard
2007-01-01
pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...
Phytochemical and pharmacological overview on Liriopes radix
African Journals Online (AJOL)
Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee. University ... has been used as a therapeutic drug for the treatment of ..... Alzheimer's disease (AD) is characterized by.
2011 Annual Meeting of the Safety Pharmacology Society: an overview.
Cavero, Icilio
2012-03-01
The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization
ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS
Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.
2014-01-01
Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971
A Survey of State Boards of Optometry Concerning Educational Requirements in Pharmacology.
Lesher, Gary A.
1986-01-01
Results of a survey of state optometry licensing requirements for coursework in pharmacology, intended as a tool for optometry curriculum development, suggest a need for training in pharmacology in both the college curriculum and continuing education. (MSE)
Pharmacological management of chronic obstructive pulmonary ...
African Journals Online (AJOL)
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 ...
Some Pharmacological Aspects of Antimalarial Drugs
African Journals Online (AJOL)
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;.
Ethnobotanical, phytochemical and pharmacological properties of ...
African Journals Online (AJOL)
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 ...
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.
Taiwan consensus of pharmacological treatment for bipolar disorder
Directory of Open Access Journals (Sweden)
Ya-Mei Bai
2013-10-01
Full Text Available Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN – the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP. The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts’ experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.
Pharmacological management of panic disorder
Directory of Open Access Journals (Sweden)
Carlo Marchesi
2008-03-01
Full Text Available Carlo MarchesiPsychiatric Section, Department of Neuroscience, University of Parma, Parma, ItalyAbstract: Panic disorder (PD is a disabling condition which appears in late adolescence or early adulthood and affects more frequently women than men. PD is frequently characterized by recurrences and sometimes by a chronic course and, therefore, most patients require longterm treatments to achieve remission, to prevent relapse and to reduce the risks associated with comorbidity. Pharmacotherapy is one of the most effective treatments of PD. In this paper, the pharmacological management of PD is reviewed. Many questions about this effective treatment need to be answered by the clinician and discussed with the patients to improve her/his collaboration to the treatment plan: which is the drug of choice; when does the drug become active; which is the effective dose; how to manage the side effects; how to manage nonresponse; and how long does the treatment last. Moreover, the clinical use of medication in women during pregnancy and breastfeeding or in children and adolescents was reviewed and its risk-benefit balance discussed.Keywords: panic disorder, pharmacological treatment, treatment guidelines
Neuroscience of behavioral and pharmacological treatments for addictions
Potenza, Marc N.; Sofuoglu, Mehmet; Carroll, Kathleen M.; Rounsaville, Bruce J.
2011-01-01
Summary Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly those derived from new findings regarding of the neurobiological underpinnings of addictions, while assimilating and incorporating relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. PMID:21338880
The internet as a tool in clinical pharmacology
Castel, Josep-Maria; Figueras, Albert; Vigo, Joan-Miquel
2006-01-01
The invention of the internet and the world-wide web was a landmark that has affected many aspects of everyday life, but is so recent and dynamic that many of its potential uses are still being explored. Aside from its purely commercial use as a virtual pharmacy (e-commerce), the internet is useful in at least three aspects related to clinical pharmacology: communication, training and research. In this paper we briefly review several internet applications related to clinical pharmacology and describe, as an example, the logistics of a multicentre research collaboration related to the promotion of rational drug use in the prevention of postpartum haemorrhage. PMID:16722847
Perception-Action in children with ASD
Directory of Open Access Journals (Sweden)
Claes eVon Hofsten
2012-12-01
Full Text Available How do disturbances to perception and action relate to the deficiencies expressed by children with autism? The ability to predict what is going to happen next is crucial for the construction of all actions and children develop these predictive abilities early in development. Children with autism, however, are deficient in the ability to foresee future events and to plan movements and movement sequences. They are also deficient in the understanding of other people’s actions. This includes communicative actions as they are ultimately based on movements. Today there are two promising neurobiological interpretation of ASD. First, there is strong evidence that the Mirror Neuron System (MNS is impaired. As stated by this hypothesis, action production and action understanding are intimately related. Both these functions rely on predictive models of the sensory consequences of actions and depend on connectivity between the parietal and pre-motor areas. Secondly, action prediction is accomplished through a system that includes a loop from the posterior parietal cortex through the cerebellum and back to the premotor and motor areas of the brain. Impairment of this loop is probably also part of the explanation of the prediction problems in children with ASD. Both the cortico-cerebellar loop and the MNS rely on distant neural connections. There are multiple evidence that such connections are weak in children with autism.
Jatropha Tanjorensis - Review of Phytochemistry, Pharmacology ...
African Journals Online (AJOL)
Based on the findings of this work, future study on the phytochemistry and chemical constituents in relation to certain other biological activities are required to fully understand the phytochemical and complex pharmacological effect of the plant specie. Further work to isolate active compounds from the plant is also necessary.
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
Pharmaceutical and pharmacological approaches for bioavailability
Indian Academy of Sciences (India)
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 ...
Chemical constituents, and pharmacological and toxicological ...
African Journals Online (AJOL)
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.
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 ...
Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle
Storella, R. J.; Schouchoff, A. L.; Fujii, M.; Hill, J.; Fletcher, J. E.; Jiang, M. S.; Smith, L. A.
1992-01-01
Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.
Forensic pharmacology: An important and evolving subspecialty needs recognition in India
Malve, Harshad Onkarrao
2016-01-01
With training in pharmacology, a pharmacologist has an expert knowledge as well as working experience in the subjects of therapeutics, pharmacokinetics, and toxicology along with exposure to subjects such as forensic medicine during the medical education. All these knowledge domains can be applied and act as an interface to the forensic situations. The skills and expertise of a forensic pharmacologist can be useful in a large and diverse number of legal cases. With an ever increasing incidence of criminal and civil cases in India, the development and inclusion of forensic pharmacologist in the judicial system of India are the need of the hour. The research in pharmacology has witnessed great technological advancement that allows it to expand its scope beyond the domain of therapeutics, thus enabling Indian pharmacologists to explore the niche area of Forensic Pharmacology. Differing pharmacokinetics and pharmacodynamics of drugs in living and dead, drug interactions, abuse of drugs, personal injury or death due to drug exposure leading to medico-legal issues, environmental exposure to chemicals, and doping and forensic pharmacovigilance are the diverse aspects of Forensic Pharmacology. PMID:27134459
Forensic pharmacology: An important and evolving subspecialty needs recognition in India
Directory of Open Access Journals (Sweden)
Harshad Onkarrao Malve
2016-01-01
Full Text Available With training in pharmacology, a pharmacologist has an expert knowledge as well as working experience in the subjects of therapeutics, pharmacokinetics, and toxicology along with exposure to subjects such as forensic medicine during the medical education. All these knowledge domains can be applied and act as an interface to the forensic situations. The skills and expertise of a forensic pharmacologist can be useful in a large and diverse number of legal cases. With an ever increasing incidence of criminal and civil cases in India, the development and inclusion of forensic pharmacologist in the judicial system of India are the need of the hour. The research in pharmacology has witnessed great technological advancement that allows it to expand its scope beyond the domain of therapeutics, thus enabling Indian pharmacologists to explore the niche area of Forensic Pharmacology. Differing pharmacokinetics and pharmacodynamics of drugs in living and dead, drug interactions, abuse of drugs, personal injury or death due to drug exposure leading to medico-legal issues, environmental exposure to chemicals, and doping and forensic pharmacovigilance are the diverse aspects of Forensic Pharmacology.
Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor
Ferrie, Ann M.; Sun, Haiyan; Fang, Ye
2011-07-01
We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.
Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review
Directory of Open Access Journals (Sweden)
Rianne A. de Kleine
2013-10-01
Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.
Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.
de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes
2013-10-17
There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.
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.
Dell'Osso, Bernardo; Camuri, Giulia; Benatti, Beatrice; Buoli, Massimiliano; Altamura, A Carlo
2013-11-01
The latency to first pharmacological treatment (duration of untreated illness or 'DUI') is supposed to play a major role in terms of outcome in psychotic conditions. Interest in the field of affective disorders and, in particular, of duration of untreated anxiety, has been recently registered as well. However, a preliminary epidemiologic investigation of the phenomenon is necessary. The present study was aimed to investigate and compare age at onset, age at first pharmacological treatment and DUI in a sample of patients affected by different anxiety disorders. DUI was defined as the interval between the onset of the specific anxiety disorder and the administration of the first adequate pharmacological treatment in compliant subjects. Study sample included 350 patients, of both sexes, with a DSM-IV-TR diagnosis of panic disorder (n = 138), generalized anxiety disorder (n = 127) and obsessive-compulsive disorder (n = 85). Panic disorder was associated with the shortest DUI (39.5 months), whereas obsessive-compulsive disorder was associated with the longest latency to treatment (94.5 months) (F = 13.333; P anxiety disorder showed a mean DUI of 81.6 months. Present results indicate that patients with different anxiety disorders may wait for years (from 3 up to 8) before receiving a first adequate pharmacological treatment. Differences in terms of age at onset, age at the first pharmacological treatment and, ultimately, in DUI in specific anxiety disorders may depend on multiple clinical and environmental factors. Latency to non-pharmacological interventions (e.g. psychoeducation and different forms of psychotherapy) needs to be addressed and correlated with DUI in future studies. © 2013 Wiley Publishing Asia Pty Ltd.
Molecular Pharmacology of CXCR4 inhibition
DEFF Research Database (Denmark)
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...
Clinical Pharmacology of Fentanyl in Preterm Infants. A Review
Directory of Open Access Journals (Sweden)
Gian Maria Pacifici
2015-06-01
Full Text Available Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.
Imaging tools to study pharmacology: functional MRI on small rodents
Elisabeth eJonckers; Disha eShah; Julie eHamaide; Marleen eVerhoye; Annemie eVan Der Linden
2015-01-01
Functional Magnetic Resonance Imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimu...