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Clinical pharmacology

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https://www.readbyqxmd.com/read/28449232/safety-pharmacokinetics-and-pharmacologic-effects-of-the-selective-androgen-receptor-modulator-gsk2881078-in-healthy-men-and-postmenopausal-women
#1
Richard V Clark, Ann C Walker, Susan Andrews, Philip Turnbull, Jeffrey A Wald, Mindy H Magee
AIM: Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first-in-human study, we report safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the SARM GSK2881078. METHODS: In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching-placebo). In Part B, repeat-dose cohorts in men (n = 65) were 0...
April 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28448998/efficacy-safety-and-tolerability-of-armodafinil-therapy-for-hypersomnia-associated-with-dementia-with-lewy-bodies-a-pilot-study
#2
Maria I Lapid, Karen M Kuntz, Sara S Mason, Jeremiah A Aakre, Emily S Lundt, Walter Kremers, Laura A Allen, Daniel A Drubach, Bradley F Boeve
BACKGROUND/AIMS: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. METHODS: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks...
April 28, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28448965/neuroprotective-treatments-after-perinatal-hypoxic-ischemic-brain-injury-evaluated-with-magnetic-resonance-spectroscopy
#3
Hester Rijkje Berger, Eva Brekke, Marius Widerøe, Tora Sund Morken
Perinatal hypoxic-ischemic brain injury is a major health problem. Adjuvant treatments that improve the neuroprotective effect of the current treatment, therapeutic hypothermia, are urgently needed. The growing knowledge about the complex pathophysiology of hypoxia-ischemia (HI) has led to the discovery of several important targets for neuroprotection. Early interventions should focus on the preservation of energy metabolism, the reduction of glutamate excitotoxicity and oxidative stress, the maintenance of calcium homeostasis, and the prevention of apoptosis...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28447879/the-lived-experience-of-caregivers-of-persons-with-heart-failure-a-phenomenological-study
#4
Antonio Petruzzo, Marco Paturzo, Monica Naletto, Marlene Z Cohen, Rosaria Alvaro, Ercole Vellone
BACKGROUND: Heart failure (HF) patients need to follow a strict pharmacological and nonpharmacological regimen in order to counteract the burden of the disease, and informal caregivers are an important resource for HF patients in managing and coping with their disease. Few studies have examined the lived experience of these caregivers with a rigorous phenomenological approach, and none have been conducted in Italy. AIM: To describe the lived experience of the caregivers of HF patients...
April 1, 2017: European Journal of Cardiovascular Nursing
https://www.readbyqxmd.com/read/28447626/familial-hyperaldosteronism-type-iii
#5
REVIEW
S Monticone, M Tetti, J Burrello, F Buffolo, R De Giovanni, F Veglio, T A Williams, P Mulatero
Primary aldosteronism is the most common form of endocrine hypertension. This disorder comprises both sporadic and familial forms. Four familial forms of primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called GIRK4). These mutations alter the selectivity filter of the channel and lead to abnormal ion currents with loss of potassium selectivity, sodium influx and consequent increased intracellular calcium that causes excessive aldosterone biosynthesis...
April 27, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28447074/chidamide-tablets-hdac-inhibition-to-treat-lymphoma
#6
Y Xu, P Zhang, Y Liu
Chidamide is the first oral subtype-selective histone deacetylase inhibitor (HDACI) approved in China as well as the first HDACI of the benzamide class approved for the treatment of relapsed and refractory peripheral T-cell lymphoma (PTCL). This review addresses detailed information regarding chidamide, including the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, clinical studies and application, safety, drug interactions and ongoing clinical trials. Although twice-weekly chidamide monotherapy has been recommended based on the evidence from preclinical and clinical studies with tolerable toxicities, its clinical efficacy could be further increased by combination with multidrug chemotherapy or chemo-free regimens...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28446883/in-vitro-and-in-vivo-profile-of-ppl-101-and-ppl-103-mixed-opioid-partial-agonist-analgesics-with-low-abuse-potential
#7
Taline V Khroyan, Andrea Cippitelli, Nicholas Toll, John A Lawson, William Crossman, Willma E Polgar, Lawrence Toll
Opiates are still the most effective and widely used treatments for acute and chronic pain. However, the problems associated with morphine and other standard opioid analgesics severely limit their effectiveness in the clinic. PPL-101 and PPL-103 derived from morphine and morphinan ring systems contain a chiral N-substituent, which confers it with a unique combination of high-binding affinities and partial agonist activities at mu, delta, and kappa opioid receptors, leading to unique in vivo pharmacology compared to other conventional opioids...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28446826/a-systematic-and-mechanistic-review-on-the-phytopharmacological-properties-of-alhagi-species
#8
REVIEW
Mohammad Hossein Asghari, Marjan Fallah, Milad Moloudizargari, Fatemeh Mehdikhani, Peyman Sepehrnia, Bigard Moradi
Alhagi species are well known in Iran (locally known as Khar Shotor) and other parts of Asia as a popular folk medicine. Recent research has shown extensive pharmacological effects of these species. This paper is a comprehensive review of the phytopharmacological effects and traditional uses of Alhagi species and their active constituents with special attention to the responsible mechanisms, effective dosages and routes of administration. The Alhagi species studied in this paper include: A. maurorum, A. camelorum, A...
October 2016: Ancient Science of Life
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#9
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28446515/role-of-biomarkers-for-the-prevention-assessment-and-management-of-heart-failure-a-scientific-statement-from-the-american-heart-association
#10
REVIEW
Sheryl L Chow, Alan S Maisel, Inder Anand, Biykem Bozkurt, Rudolf A de Boer, G Michael Felker, Gregg C Fonarow, Barry Greenberg, James L Januzzi, Michael S Kiernan, Peter P Liu, Thomas J Wang, Clyde W Yancy, Michael R Zile
BACKGROUND AND PURPOSE: Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28446243/targeting-metabotropic-glutamate-receptors-for-novel-treatments-of-schizophrenia
#11
REVIEW
James Maksymetz, Sean P Moran, P Jeffrey Conn
Support for the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia has led to increasing focus on restoring proper glutamatergic signaling as an approach for treatment of this devastating disease. The ability of metabotropic glutamate (mGlu) receptors to modulate glutamatergic neurotransmission has thus attracted considerable attention for the development of novel antipsychotics. Consisting of eight subtypes classified into three groups based on sequence homology, signal transduction, and pharmacology, the mGlu receptors provide a wide range of targets to modulate NMDAR function as well as glutamate release...
April 26, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28445815/lc-ms-ms-determination-of-tranexamic-acid-in-human-plasma-after-phospholipid-clean-up
#12
Nicolas Fabresse, Fanta Fall, Isabelle Etting, Philippe Devillier, Jean-Claude Alvarez, Stanislas Grassin-Delyle
Tranexamic acid is a widely used antifibrinolytic drug but its pharmacology and pharmacokinetics remains poorly understood. Owing to the recent knowledge on phospholipid-induced matrix effects during human plasma analysis, our aim was to develop a liquid chromatography-mass spectrometry method for the quantitation of tranexamic acid after efficient sample clean-up. Sample preparation consisted in phospholipid removal and protein precipitation. Hydrophilic interaction liquid chromatography was used and the detection was achieved with multiple reaction monitoring...
April 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28445709/gait-analysis-and-weight-bearing-in-pre-clinical-joint-pain-research
#13
Kristina Ängeby Möller, Heta Svärd, Anni Suominen, Jarmo Immonen, Johanna Holappa, Carina Stenfors
BACKGROUND: There is a need for better joint pain treatment, but development of new medication has not been successful. Pre-clinical models with readouts that better reflect the clinical situation are needed. In patients with joint pain, pain at rest and pain at walking are two major complaints. NEW METHOD: We describe a new way of calculating results from gait analysis using the CatWalk™ setup. Rats with monoarthritis induced by injection of Complete Freund's Adjuvant (CFA) intra-articularly into the ankle joint of one hind limb were used to assess gait and dynamic weight bearing...
April 23, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28445191/evaluation-of-horner-syndrome-in-the-mri-era
#14
Ama Sadaka, Samantha L Schockman, Karl C Golnik
BACKGROUND: To identify the etiologies of adult Horner syndrome (HS) in the MRI era using a targeted evaluation approach and to assess the value and yield of targeted imaging. METHODS: A retrospective chart review was performed of 200 adult outpatients with HS, confirmed with cocaine eyedrop testing. Patients were divided into subgroups based on the presence or absence of symptoms and those who did or did not receive additional testing with hydroxyamphetamine drops...
April 25, 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/28445187/the-effects-of-inherited-nudt15-polymorphisms-on-thiopurine-active-metabolites-in-japanese-children-with-acute-lymphoblastic-leukemia
#15
Takaya Moriyama, Rina Nishii, Ting-Nien Lin, Kentaro Kihira, Hidemi Toyoda, Nersting Jacob, Motohiro Kato, Katsuyoshi Koh, Hiroto Inaba, Atsushi Manabe, Kjeld Schmiegelow, Jun J Yang, Hiroki Hori
Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major genetic cause for MP-related bone marrow suppression, and there is increasing interest in the clinical implementation of NUDT15 genotype-guided MP dose individualization. Therefore, we sought to evaluate the effects of NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform NUDT15 genotype-guided MP dosing...
April 25, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28445140/triple-negative-breast-cancer-the-kiss-of-death
#16
REVIEW
Adriana-Andreea Jitariu, Anca Maria Cîmpean, Domenico Ribatti, Marius Raica
One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are critically overviewed here, being focused on data useful in clinical practice or to improve the therapy and patients survival. TNBCs "choose" young women and its "kiss" is, unfortunately deadly in most cases. Currently, few sparse data are available in literature concerning the origins of TNBC. Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of CD133+ cells and may be stimulated by different pharmacological agents such sunitinib...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445082/the-impact-of-%C3%AE-amyloid-positron-emission-tomography-on-the-diagnostic-and-treatment-decisions-of-dementia-experts
#17
Michael L Ganz, Alie F Tawah, Shien Guo, Abhishek S Chitnis, Hedwig Silies, Barbara Schäuble, Aleksandar Jovalekic, Norman L Foster
AIM: Amyloid positron emission tomography (aPET) measurement of Alzheimer's disease (AD) pathology could improve the accurate diagnosis of cognitive disorders. Appropriate use criteria recommend that only dementia experts order aPET. MATERIALS & METHODS: We surveyed 145 dementia experts about their current approaches to evaluation and treatment and the likely influence of aPET. RESULTS: Experts expected aPET to alter diagnostic procedures and patient management and also increase diagnostic certainty...
April 26, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28444695/exercise-therapy-for-chronic-fatigue-syndrome
#18
REVIEW
Lillebeth Larun, Kjetil G Brurberg, Jan Odgaard-Jensen, Jonathan R Price
BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28444684/-evaluation-and-treatment-of-sleep-problems-in-children-diagnosed-with-attention-deficit-hyperactivity-disorder-an-update-of-the-evidence
#19
REVIEW
M Chamorro, J P Lara, I Insa, M Espadas, J A Alda-Diez
INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) affects approximately 5% of all children and adolescents, and these patients frequently suffer from sleep problems. The association between sleep disorders and ADHD, however, is multifaceted and complex. AIMS: To explore the relationship between sleep disorders and ADHD. DEVELOPMENT: Sleep problems in children with ADHD include altered sleep and specific disorders per se or that may be due to comorbid psychiatric disorders or to the stimulants they receive as treatment for their ADHD...
May 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28444204/murine-models-of-sepsis-and-trauma-can-we-bridge-the-gap
#20
Julie A Stortz, Steven L Raymond, Juan C Mira, Lyle L Moldawer, Alicia M Mohr, Philip A Efron
Sepsis and trauma are both leading causes of death in the United States and represent major public health challenges. Murine models have largely been used in sepsis and trauma research to better understand the pathophysiological changes that occur after an insult and to develop potential life-saving therapeutic agents. Mice are favorable subjects for this type of research given the variety of readily available strains including inbred, outbred, and transgenic strains. In addition, they are relatively easy to maintain and have a high fecundity...
April 21, 2017: ILAR Journal
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