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Systems pharmacology

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https://www.readbyqxmd.com/read/29150145/neuroimaging-biomarkers-as-predictors-of-treatment-outcome-in-major-depressive-disorder
#1
REVIEW
Trehani M Fonseka, Glenda M MacQueen, Sidney H Kennedy
BACKGROUND: Current practice for selecting pharmacological and non-pharmacological antidepressant treatments has yielded low response and remission rates in Major Depressive Disorder (MDD). Neuroimaging biomarkers of brain structure and function may be useful in guiding treatment selection by predicting response vs. non-response outcomes. METHODS: In this review, we summarize data from studies examining predictors of treatment response using structural and functional neuroimaging modalities, as they pertain to pharmacotherapy, psychotherapy, and stimulation treatment strategies...
October 31, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29149325/the-iuphar-bps-guide-to-pharmacology-in-2018-updates-and-expansion-to-encompass-the-new-guide-to-immunopharmacology
#2
Simon D Harding, Joanna L Sharman, Elena Faccenda, Chris Southan, Adam J Pawson, Sam Ireland, Alasdair J G Gray, Liam Bruce, Stephen P H Alexander, Stephen Anderton, Clare Bryant, Anthony P Davenport, Christian Doerig, Doriano Fabbro, Francesca Levi-Schaffer, Michael Spedding, Jamie A Davies
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29149154/philosophical-issues-and-psychological-variables-that-influence-the-determination-of-opioid-effectiveness-a-narrative-review
#3
Daniel Michael Doleys
BACKGROUND: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked. OBJECTIVES: This manuscript provides a selective review and narrative summary of the philosophical issues and psychological factors which can influence opioid effectiveness...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29147678/a-haplotype-associated-with-enhanced-mineralocorticoid-receptor-expression-facilitates-the-stress-induced-shift-from-cognitive-to-habit-learning
#4
Lisa Wirz, Martin Reuter, Jan Wacker, Andrea Felten, Lars Schwabe
Stress induces a shift from hippocampus-dependent "cognitive" toward dorsal striatum-dependent "habit" memory. However, not all individuals are susceptible to this shift under stress. Based on pharmacological studies indicating a critical role of the mineralocorticoid receptor (MR) in the stress-induced bias toward dorsal striatal learning, we hypothesized that MR gene variants contribute to these individual differences. In two experiments, healthy participants were genotyped, exposed to a stressor or control manipulation and performed a learning task that can be solved using hippocampal or dorsal striatal systems, while electroencephalography (EEG; Experiment I) or functional magnetic resonance imaging (fMRI; Experiment II) measurements were taken...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29146949/a-microfluidic-platform-for-the-characterisation-of-cns-active-compounds
#5
Christopher MacKerron, Graham Robertson, Michele Zagnoni, Trevor J Bushell
New in vitro technologies that assess neuronal excitability and the derived synaptic activity within a controlled microenvironment would be beneficial for the characterisation of compounds proposed to affect central nervous system (CNS) function. Here, a microfluidic system with computer controlled compound perfusion is presented that offers a novel methodology for the pharmacological profiling of CNS acting compounds based on calcium imaging readouts. Using this system, multiple applications of the excitatory amino acid glutamate (10 nM-1 mM) elicited reproducible and reversible transient increases in intracellular calcium, allowing the generation of a concentration response curve...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146527/osthole-attenuates-right-ventricular-remodeling-via-decreased-myocardial-apoptosis-and-inflammation-in-monocrotaline-induced-rats
#6
Yeli Li, Yiqi Li, Fuguo Shi, Lina Wang, Lisheng Li, Danli Yang
Osthole (Ost) is a coumarin that exhibits wide pharmacological effects in the cardiovascular system. However, whether Ost can inhibit apoptosis and inflammation in right ventricle (RV) cardiomyocytes and prevent RV remodeling is not clear. This study was designed to investigate the effect of Ost on RV remodeling and the underlying mechanism. By applying a monocrotaline (MCT)-induced rat model, the effect of Ost on RV remodeling was investigated. Rats were given a single dose of MCT (50mg⁄kg) subcutaneously (s...
November 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29146502/protracted-motivational-dopamine-related-deficits-following-adolescence-sugar-overconsumption
#7
Fabien Naneix, Florence Darlot, Véronique De Smedt-Peyrusse, Jean-Rémi Pape, Etienne Coutureau, Martine Cador
Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146243/current-progress-and-challenges-of-nanoparticle-based-therapeutics-in-pain-management
#8
REVIEW
Vanesa Andreu, Manuel Arruebo
Pain is a widespread and growing health problem worldwide that exerts a considerable social and economic impact on both patients and healthcare systems and, therefore, on society in general. Although current treatment modalities include a wide variety of pharmacological and non-pharmacological approaches, due to the complexity of pain and individual differences in clinical response these options are not always effective in mitigating and relieving pain. In addition, some pain drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids show several unfavorable side effects...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29144508/ly6g-neutrophil-derived-mir-223-inhibits-the-nlrp3-inflammasome-in-mitochondrial-damp-induced-acute-lung-injury
#9
Zunyong Feng, Shimei Qi, Yue Zhang, Zhilin Qi, Liang Yan, Jing Zhou, Fang He, Qianqian Li, Yanyan Yang, Qun Chen, Shi Xiao, Qiang Li, Yang Chen, Yao Zhang
MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29142416/protective-effect-of-pluchea-lanceolata-against-aluminum-chloride-induced-neurotoxicity-in-swiss-albino-mice
#10
Ravi Mundugaru, Senthilkumar Sivanesan, Padmaja Udaykumar, Niranjan Rao, Naveen Chandra
Background: Aluminum chloride (AlCl3) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb Pluchea lanceolata is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine. Objective: To evaluate the neuroprotective activity of hydroalcoholic extract of P. lanceolata in chronic AlCl3-induced neurotoxicity in Swiss albino mice. Materials and Methods: Albino mice were categorized into four different groups; Group 1served as vehicle control, Group 2 mice were administered with AlCl3, 40 mg/kg body weight by intraperitoneal route for 45 consecutive days...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29141964/acute-decompensated-pulmonary-hypertension
#11
Laurent Savale, Jason Weatherald, Xavier Jaïs, Constance Vuillard, Athénaïs Boucly, Mitja Jevnikar, David Montani, Olaf Mercier, Gerald Simonneau, Elie Fadel, Olivier Sitbon, Marc Humbert
Acute right heart failure in chronic precapillary pulmonary hypertension is characterised by a rapidly progressive syndrome with systemic congestion resulting from impaired right ventricular filling and/or reduced right ventricular flow output. This clinical picture results from an imbalance between the afterload imposed on the right ventricle and its adaptation capacity. Acute decompensated pulmonary hypertension is associated with a very poor prognosis in the short term. Despite its major impact on survival, its optimal management remains very challenging for specialised centres, without specific recommendations...
December 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/29141695/methylxanthines-induce-structural-and-functional-alterations-of-the-cardiac-system-in-zebrafish-embryos
#12
Ram Manohar Basnet, Daniela Zizioli, Michela Guarienti, Dario Finazzi, Maurizio Memo
BACKGROUND: Zebrafish embryos are emerging as a model for pharmacological and toxicological studies. We used zebrafish embryos to study the general toxicity and cardiovascular effects of eight methylxanthines: aminophylline, caffeine, diprophylline, doxofylline, etophylline, 3-isobutyl-1-methylxanthine (IBMX), pentoxifylline and theophylline. METHODS: Microinjections of the eight methylxanthines were performed in 1-2 cell stage zebrafish embryos and the general toxicity and cardiovascular effects were analyzed at different time points...
November 15, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29141007/escitalopram-and-nht-normalized-stress-induced-anhedonia-and-molecular-neuroadaptations-in-a-mouse-model-of-depression
#13
Or Burstein, Motty Franko, Eyal Gale, Assaf Handelsman, Segev Barak, Shai Motsan, Alon Shamir, Roni Toledano, Omri Simhon, Yafit Hirshler, Gang Chen, Ravid Doron
Anhedonia is defined as a diminished ability to obtain pleasure from otherwise positive stimuli. Anxiety and mood disorders have been previously associated with dysregulation of the reward system, with anhedonia as a core element of major depressive disorder (MDD). The aim of the present study was to investigate whether stress-induced anhedonia could be prevented by treatments with escitalopram or novel herbal treatment (NHT) in an animal model of depression. Unpredictable chronic mild stress (UCMS) was administered for 4 weeks on ICR outbred mice...
2017: PloS One
https://www.readbyqxmd.com/read/29140557/withdrawn-pharmacological-cardioversion-for-atrial-fibrillation-and-flutter
#14
REVIEW
John Cordina, Gillian E Mead
BACKGROUND: Atrial fibrillation is the commonest cardiac dysrhythmia. It is associated with significant morbidity and mortality. There are two approaches to the management of atrial fibrillation: controlling the ventricular rate or converting to sinus rhythm in the expectation that this would abolish its adverse effects. OBJECTIVES: To assess the effects of pharmacological cardioversion of atrial fibrillation in adults on the annual risk of stroke, peripheral embolism, and mortality...
November 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29140431/microvascular-adaptations-to-exercise-protective-effect-of-pgc-1-alpha
#15
Andrew O Kadlec, Chad Barnes, Matthew J Durand, David D Gutterman
BACKGROUND: Sedentary behavior and obesity are major risk factors for cardiovascular disease. Regular physical activity has independent protective effects on the cardiovascular system, but the mechanisms responsible remain elusive. Recent studies suggest that the protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) participates in the response to exercise training. We hypothesized that the arterioles of athletes maintain dilation to flow despite combined inhibition of multiple vasodilators, but loss of PGC-1α renders these vessels susceptible to inhibition of a single vasodilator pathway...
November 11, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/29139546/up-regulation-of-pyk2-pkc%C3%AE-dependent-ho-1-by-co-releasing-molecule-corm-2-attenuates-tnf-%C3%AE-induced-lung-inflammation
#16
Chih-Chung Lin, Yu-Ching Chiang, Rou-Ling Cho, Wei-Ning Lin, Chien-Chung Yang, Li-Der Hsiao, Chuen-Mao Yang
BACKGROUND AND PURPOSE: Heme oxygenase-1 (HO-1) could provide cytoprotection against various inflammatory diseases. However, the mechanisms underlying carbon monoxide-releasing molecule-2 (CORM-2)-induced HO-1 expression protecting against TNF-α-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown. EXPERIMENTAL APPROACH: CORM-2-induced HO-1 protein and mRNA expression, and signaling pathways were determined by Western blot and real-time PCR, coupled using respective pharmacological inhibitors or transfection with siRNAs...
November 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29139482/opioid-misuse-in-gastroenterology-and-non-opioid-management-of-abdominal-pain
#17
REVIEW
Eva Szigethy, Mitchell Knisely, Douglas Drossman
Opioids were one of the earliest classes of medications used for pain across a variety of conditions, but morbidity and mortality have been increasingly associated with their chronic use. Despite these negative consequences, chronic opioid use is increasing worldwide, with the USA and Canada having the highest rates. Chronic opioid use for noncancer pain can have particularly negative effects in the gastrointestinal and central nervous systems, including opioid-induced constipation, narcotic bowel syndrome, worsening psychopathology and addiction...
November 15, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29139091/pharmacological-approach-to-the-management-of-crohn-s-disease-patients-with-perianal-disease
#18
REVIEW
Fernando Bermejo, Iván Guerra, Alicia Algaba, Antonio López-Sanromán
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators...
November 14, 2017: Drugs
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#19
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29136276/targeted-therapies-immunologic-effects-and-potential-applications-outside-of-cancer
#20
REVIEW
Anna E Kersh, Spencer Ng, Yun Min Chang, Maiko Sasaki, Susan N Thomas, Haydn T Kissick, Gregory B Lesinski, Ragini R Kudchadkar, Edmund K Waller, Brian P Pollack
Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment...
November 14, 2017: Journal of Clinical Pharmacology
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