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Clinical pharmacology

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https://www.readbyqxmd.com/read/29351246/addition-of-berberine-to-preservation-solution-in-an-animal-model-of-ex-vivo-liver-transplant-preserves-mitochondrial-function-and-bioenergetics-from-the-damage-induced-by-ischemia-reperfusion
#1
Rui Miguel Martins, Anabela Pinto Rolo, João Soeiro Teodoro, Emanuel Furtado, Rui Caetano Oliveira, José Guilherme Tralhão, Carlos Marques Palmeira
Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#2
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29351198/superoxide-dismutase-mimetic-gc4419-enhances-the-oxidation-of-pharmacological-ascorbate-and-its-anticancer-effects-in-an-h%C3%A2-o%C3%A2-dependent-manner
#3
Collin D Heer, Andrew B Davis, David B Riffe, Brett A Wagner, Kelly C Falls, Bryan G Allen, Garry R Buettner, Robert A Beardsley, Dennis P Riley, Douglas R Spitz
Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several cancer types...
January 19, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29351005/an-integrated-operational-definition-and-conceptual-model-of-asthma-self-management-in-teens
#4
Jennifer Mammen, Hyekyun Rhee, Sally A Norton, Arlene M Butz, Jill S Halterman, Kimberly Arcoleo
OBJECTIVES: A previous definition of adolescent asthma self-management was derived from interviews with clinicians/researchers and published literature; however, it did not incorporate perspectives of teens or parents. Therefore, we conducted in-depth interviews with teens and parents and synthesized present findings with the prior analysis to develop a more encompassing definition and model. METHODS: Focal concepts were qualitatively extracted from 14-day self-management voice-diaries (n = 14) and 1-hour interviews (n = 42) with teens and parents (28 individuals) along with concepts found in the previous clinical/research oriented analysis...
January 19, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29350758/obesity-and-pediatric-drug-development
#5
Janelle D Vaughns, Laurie S Conklin, Ying Long, Panli Zheng, Fahim Faruque, Dionna J Green, John N van den Anker, Gilbert J Burckart
There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies...
January 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29350320/ethical-implications-in-vaccine-pharmacotherapy-for-treatment-and-prevention-of-drug-of-abuse-dependence
#6
Anna Carfora, Paola Cassandro, Alessandro Feola, Francesco La Sala, Raffaella Petrella, Renata Borriello
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway...
January 19, 2018: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/29350019/cypress-pollen-allergy-is-responsible-for-two-distinct-phenotypes-of-allergic-rhinitis-different-from-other-pollinosis
#7
L Pahus, M Gouitaa, T Sofalvi, K Alagha, D Gras, P Chanez, D Charpin
Different phenotypes of allergic rhinitis have been identified based on the seasonality of the allergen involved. Within pollinosis, importance has to be paid to the responsible pollen species. Guidelines for clinical management are mostly based on studies performed in patients with grass pollen allergy. Only few data is available on tree pollen allergy and more specifically on cypress pollen allergy. We focused on the clinical and biological features of cypress pollen allergy to determine whether it is associated with a specific phenotype of allergic rhinitis or not...
January 2018: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29349890/case-report-cytochrome-p450-implications-for-comorbid-adhd-and-ocd-pharmacotherapy
#8
Michaela K Hogan, Nikhil P Rao
TOPIC: This case report details the treatment of an early adolescent already receiving treatment for attention-deficit hyperactivity disorder who presents with recurrent obsessive-compulsive disorder. Potential atomoxetine (Strattera) and fluoxetine (Prozac) interactions via Cytochrome P450 (CYP450) pathways are examined and alternate therapies are recommended. PURPOSE: Provide a discussion of psychopharmacogenomics, especially in the case of combining medications, CYP450 enzymes, and clinical implications in the context of the burgeoning field of precision medicine...
January 19, 2018: Journal of Child and Adolescent Psychiatric Nursing
https://www.readbyqxmd.com/read/29349561/sphenopalatine-ganglion-stimulation-for-cluster-headache-results-from-a-large-open-label-european-registry
#9
Mads Barloese, Anja Petersen, Philipp Stude, Tim Jürgens, Rigmor Højland Jensen, Arne May
BACKGROUND: Cluster headache (CH) is a disabling primary headache disorder characterized by severe periorbital pain. A subset of patients does not respond to established pharmacological therapy. This study examines outcomes of a cohort of mainly chronic CH patients treated with sphenopalatine ganglion (SPG) stimulation. METHODS: Patients were followed in an open-label prospective study for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans-oral insertion of a microstimulator targeting the SPG...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29349551/medical-marijuana-current-concepts-pharmacological-actions-of-cannabinoid-receptor-mediated-activation-and-societal-implications
#10
REVIEW
Nalini Vadivelu, Alice M Kai, Gopal Kodumudi, Julie Sramcik, Alan D Kaye
PURPOSE OF REVIEW: The purpose of the following review is to summarize the history and current policies related to marijuana use and prevalence, basic and clinical science pharmacological literature regarding efficacy, subpopulations of concern, and varying policies regarding its use at present. RECENT FINDINGS: With the increasingly widespread utilization of marijuana, there is also a growing complexity of public health policy, regulation, and necessity to further assess the medical indications and adverse long-term effects of marijuana use...
January 18, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29348728/systems-level-mechanisms-of-action-of-panax-ginseng-a-network-pharmacological-approach
#11
REVIEW
Sa-Yoon Park, Ji-Hun Park, Hyo-Su Kim, Choong-Yeol Lee, Hae-Jeung Lee, Ki Sung Kang, Chang-Eop Kim
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...
January 2018: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#12
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#13
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29348125/metabolism-and-disposition-of-a-novel-selective-%C3%AE-7-neuronal-acetylcholine-receptor-agonist-abt-126-in-humans-characterization-of-the-major-roles-for-flavin-containing-monooxygenases-and-udp-glucuronosyl-transferase-1a4-and-2b10-in-catalysis
#14
Hong Liu, David M Stresser, Melissa J Michmerhuizen, XIaofeng Li, Ahmed A Othman, Aimee D Reed, Michael R Schrimpf, Jens Sydor, Anthony J Lee
Mass balance, metabolism and excretion of ABT-126, an α7 nAChRs agonist, were characterized in healthy male subjects (n=4) following a single 100 mg (100 μCi) oral dose. The total recovery of the administered radioactivity was 94.0% (±2.09%) with 81.5% (± 10.2%) in urine and 12.4% (± 9.3%) in feces. Metabolite profiling indicated that ABT-126 had been extensively metabolized with 6.6% of the dose remaining as unchanged parent drug in urine. Parent drug accounted for 12.2% of the administered radioactivity in feces...
January 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29348070/rational-approach-to-highly-potent-and-selective-apoptosis-signal-regulating-kinase-1-ask1-inhibitors
#15
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29347991/the-benefits-and-tolerance-of-exercise-in-myasthenia-gravis-mgex-study-protocol-for-a-randomised-controlled-trial
#16
Simone Birnbaum, Jean-Yves Hogrel, Raphael Porcher, Pierre Portero, Bernard Clair, Bruno Eymard, Sophie Demeret, Guillaume Bassez, Marcela Gargiulo, Estelle Louët, Sonia Berrih-Aknin, Asmaa Jobic, Philippe Aegerter, Philippe Thoumie, Tarek Sharshar
BACKGROUND: Research exploring the effects of physical exercise in auto-immune myasthenia gravis (MG) is scarce. The few existing studies present methodological shortcomings limiting the conclusions and generalisability of results. It is hypothesised that exercise could have positive physical, psychological as well as immunomodulatory effects and may be a beneficial addition to current pharmacological management of this chronic disease. The aim of this study is to evaluate the benefits on perceived quality of life (QOL) and physical fitness of a home-based physical exercise program compared to usual care, for patients with stabilised, generalised auto-immune MG...
January 18, 2018: Trials
https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#17
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346639/comparison-of-dopamine-d3-and-d2-receptor-occupancies-by-a-single-dose-of-blonanserin-in-healthy-subjects-a-positron-emission-tomography-study-with-11c-phno
#18
Amane Tateno, Takeshi Sakayori, Woo-Chan Kim, Kazuyoshi Honjo, Haruo Nakayama, Ryosuke Arakawa, Yoshiro Okubo
Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy males (mean 35...
January 13, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29346311/apoptotic-and-nonapoptotic-activities-of-pterostilbene-against-cancer
#19
REVIEW
Rong-Jane Chen, Hsiao-Che Kuo, Li-Hsin Cheng, Yu-Hsuan Lee, Wen-Tsan Chang, Bour-Jr Wang, Ying-Jan Wang, Hung-Chi Cheng
Cancer is a major cause of death. The outcomes of current therapeutic strategies against cancer often ironically lead to even increased mortality due to the subsequent drug resistance and to metastatic recurrence. Alternative medicines are thus urgently needed. Cumulative evidence has pointed out that pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, PS) has excellent pharmacological benefits for the prevention and treatment for various types of cancer in their different stages of progression by evoking apoptotic or nonapoptotic anti-cancer activities...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29345985/cyp3a-activity-and-rivaroxaban-serum-concentrations-in-russian-patients-with-deep-vein-thrombosis
#20
Dmitriy Alexeyevich Sychev, Arshak Vardanyan, Aleksandr Rozhkov, Edita Hachatryan, Ani Badanyan, Valery Smirnov, Anna Ananichuk, Natalya Denisenko
BACKGROUND: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters. METHODS: The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months...
January 2018: Genetic Testing and Molecular Biomarkers
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