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Clinical pharmacology

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https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#1
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28806385/a-naturalistic-comparison-of-methylphenidate-and-risperidone-monotherapy-in-drug-naive-youth-with-attention-deficit-hyperactivity-disorder-comorbid-with-oppositional-defiant-disorder-and-aggression
#2
Gabriele Masi, Azzurra Manfredi, Giulia Nieri, Pietro Muratori, Chiara Pfanner, Annarita Milone
BACKGROUND/PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version)...
August 10, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28805960/factors-associated-with-high-pain-intensity-during-wound-care-procedures-a-model
#3
Sue E Gardner, Linda I Abbott, Catherine A Fiala, Barbara A Rakel
The most common wound care procedures (WPCs) performed on open wounds are dressing changes and wound cleansing. Dressing changes cause moderate to severe pain in 74% of patients, nearly half (36%) of whom experience severe pain (rated as 8-10 on a 10-point numeric rating scale). The purpose of this paper is to propose a model of clinically accessible factors that can be tested in order to develop a clinical tool to identify which patients are likely to experience high intensity pain during nonoperative WCPs, such as dressing changes...
June 8, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28804896/load-dependence-of-myocardial-deformation-variables-a-clinical-strain-echocardiographic-study
#4
M Fredholm, K Jörgensen, E Houltz, S-E Ricksten
BACKGROUND: The effects of left ventricular (LV) loading on myocardial deformation variables are not well-studied in the clinical setting. In the present study, we evaluated the effects of isolated changes in preload, afterload and heart rate on LV longitudinal strain, systolic (SR-S) and early diastolic strain rate (SR-E) in post-cardiac surgery patients. METHODS: Twenty-one patients were studied early after cardiac surgery. Longitudinal myocardial strain and SR were analysed off-line using 2-D speckle echocardiography...
August 13, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28804763/effects-of-chest-physical-therapy-in-patients-with-non-tuberculous-mycobacteria
#5
Ashwin Basavaraj, Leopoldo Segal, Jonathan Samuels, Jeremy Feintuch, Joshua Feintuch, Kevin Alter, Daniella Moffson, Adrienne Scott, Doreen Addrizzo-Harris, Mengling Liu, David Kamelhar
Antibiotic therapy against non-tuberculous mycobacteria (NTM) is prolonged and can be associated with toxicity. We sought to evaluate whether chest physical therapy (PT) was associated with clinical improvement in patients with NTM not receiving anti-mycobacterial pharmacotherapy. A retrospective review of 77 subjects that were followed from June 2006 to September 2014 was performed. Baseline time point was defined as the first positive sputum culture for NTM; symptoms, pulmonary function, and radiology reports were studied...
2017: International Journal of Respiratory and Pulmonary Medicine
https://www.readbyqxmd.com/read/28803968/acute-spinal-cord-injury-a-review-of-pathophysiology-and-potential-of-non-steroidal-anti-inflammatory-drugs-for-pharmacological-intervention
#6
REVIEW
Emrullah Hayta, Hasan Elden
Acute spinal cord injury (SCI) is one of the serious central nervous system injuries, which can lead to significant neurological impairments and a reduction in quality of life with loss in sensory and motor functions. Although recent advancements contribute to the understanding of the underlying pathophysiological processes developed after SCI, currently, there is limited innovative and effective treatment options besides conventional rehabilitation and management of SCI to alleviate the condition. Improvements in neurological functions of the individuals with SCI depend mainly on the mechanical damage occurring in the primary injury and on pathophysiological alterations associated with secondary damage...
August 10, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28803248/a-functional-assay-for-sick-sinus-syndrome-genetic-variants
#7
Chuanchau J Jou, Cammon B Arrington, Spencer Barnett, Jiaxiang Shen, Scott Cho, Xiaoming Sheng, Patrick C McCullagh, Neil E Bowles, Chase M Pribble, Elizabeth V Saarel, Thomas A Pilcher, Susan P Etheridge, Martin Tristani-Firouzi
BACKGROUND/AIMS: Congenital Sick Sinus Syndrome (SSS) is a disorder associated with sudden cardiac death due to severe bradycardia and prolonged pauses. Mutations in HCN4, the gene encoding inward Na+/K+ current (If), have been described as a cause of congenital SSS. The objective of this study is to develop an SSS model in embryonic zebrafish, and use zebrafish as a moderate-throughput assay to functionally characterize HCN4 variants. METHODS: To determine the function of hcn4 in zebrafish, embryos were either bathed in the If -specific blocker (ZD-7288), or endogenous hcn4 expression was knocked down using splice-blocking morpholinos...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28802926/nonmotor-symptoms-and-natural-history-of-parkinson-s-disease-evidence-from-cognitive-dysfunction-and-role-of-noninvasive-interventions
#8
Roberta Biundo, Eleonora Fiorenzato, Angelo Antonini
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802779/pharmacological-aspects-of-closed-loop-insulin-delivery-for-type-1-diabetes
#9
REVIEW
Chukwuma Uduku, Nick Oliver
Insulin deficiency and impaired glucose homeostasis are hallmarks of type 1 diabetes. Since the discovery of insulin, pharmacological and clinical developments have endeavoured to replicate its endogenous pharmacokinetics (PK) and pharmacodynamics (PD). Closed loop insulin delivery systems operate as an artificial pancreas by making automated insulin dose adjustments based on real time continuous glucose monitoring. The increasing adoption of continuous insulin pump therapy and evolving technological advances have seen significant progress in the development of closed loop insulin delivery systems...
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28802583/cytoskeleton-and-nuclear-lamina-affection-in-recessive-osteogenesis-imperfecta-a-functional-proteomics-perspective
#10
Assunta Gagliardi, Roberta Besio, Chiara Carnemolla, Claudia Landi, Alessandro Armini, Mona Aglan, Ghada Otaify, Samia A Temtamy, Antonella Forlino, Luca Bini, Laura Bianchi
Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism. Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear...
August 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#11
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28801825/intractable-constipation-in-the-elderly
#12
REVIEW
Noemi Baffy, Amy E Foxx-Orenstein, Lucinda A Harris, Susan Sterler
Chronic constipation is a common gastrointestinal disorder disproportionately affecting the elderly. Immobility, polypharmacy, and physiologic changes contribute to its increased prevalence in this population. Unidentified and undertreated constipation leads to a significant negative impact on quality of life and an increase in healthcare spending. Careful physical examination and exploration of the clinical history can unmask primary and secondary forms of constipation, guiding diagnostic and therapeutic considerations...
August 11, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28801423/comparative-efficacy-and-acceptability-of-antidepressants-psychological-interventions-and-their-combination-for-depressive-disorder-in-children-and-adolescents-protocol-for-a-network-meta-analysis
#13
Xinyu Zhou, Andrea Cipriani, Yuqing Zhang, Pim Cuijpers, Sarah E Hetrick, John R Weisz, Juncai Pu, Cinzia Del Giovane, Toshiaki A Furukawa, Jürgen Barth, David Coghill, Stefan Leucht, Lining Yang, Arun V Ravindran, Peng Xie
INTRODUCTION: Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28801400/protein-misfolding-amyotrophic-lateral-sclerosis-and-guanabenz-protocol-for-a-phase-ii-rct-with-futility-design-promise-trial
#14
Eleonora Dalla Bella, Irene Tramacere, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Christian Lunetta, Jessica Mandrioli, Letizia Mazzini, Sonia Messina, Maria Rosaria Monsurrò, Gabriele Mora, Nilo Riva, Romana Rizzi, Gabriele Siciliano, Vincenzo Silani, Isabella Simone, Gianni Sorarù, Paolo Volanti, Giuseppe Lauria
INTRODUCTION: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28800937/vortioxetine-a-new-alternative-for-the-treatment-of-major-depressive-disorder
#15
Estela Salagre, Iria Grande, Brisa Solé, Jose Sanchez-Moreno, Eduard Vieta
Major Depressive Disorder (MDD) is a serious psychiatric condition. Its treatment remains a challenge nowadays. Vortioxetine is a novel antidepressant with a unique profile, as it acts as a multimodal serotoninergic agent. Its efficacy in MDD has been established in many short- and long-term studies, with 7 positive, 4 negative and 1 failed randomized controlled trials. Moreover, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers vortioxetine pro-cognitive effects...
August 8, 2017: Revista de Psiquiatrí́a y Salud Mental
https://www.readbyqxmd.com/read/28800738/advances-in-closed-loop-deep-brain-stimulation-devices
#16
REVIEW
Mahboubeh Parastarfeizabadi, Abbas Z Kouzani
BACKGROUND: Millions of patients around the world are affected by neurological and psychiatric disorders. Deep brain stimulation (DBS) is a device-based therapy that could have fewer side-effects and higher efficiencies in drug-resistant patients compared to other therapeutic options such as pharmacological approaches. Thus far, several efforts have been made to incorporate a feedback loop into DBS devices to make them operate in a closed-loop manner. METHODS: This paper presents a comprehensive investigation into the existing research-based and commercial closed-loop DBS devices...
August 11, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28800184/use-of-non-pharmacological-strategies-for-pain-relief-in-addiction-treatment-patients-with-chronic-pain
#17
Lewei Allison Lin, Amy S B Bohnert, Mary Jannausch, Jenna Goesling, Mark A Ilgen
BACKGROUND AND OBJECTIVES: We examined use of non-pharmacological treatments for pain in addiction treatment patients. METHODS: Patients in addiction treatment with chronic pain (N = 501) were classified based on use of non-pharmacological pain treatments. Demographic and clinical correlates were compared. RESULTS: A total of 49% (N = 243) of patients used a non-pharmacological treatment in the past year versus 72% (N = 361) who used opioids...
August 11, 2017: American Journal on Addictions
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#18
Gaetano Zaccara, D Schmidt
BACKGROUND: Animal models when carefully selected, designed and conducted, are important parts of any translational drug development strategy. However, research of new compounds for patients with drug-resistant epilepsies is still based on animal experiments, mostly in rodents, which are far from being a model of chronic human epilepsy and have failed to differentiate the efficacy of new compounds versus standard drug treatment. Objective The objective was identification and description of compounds in clinical development in 2016...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799510/safety-profile-of-the-newest-antiepileptic-drugs-a-curated-literature-review
#19
Caterina Palleria, Giuseppe Cozza, Rajeshree Khengar, Vincenzo Libri, Giovambattista De Sarro
BACKGROUND: Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799414/the-clinical-use-of-a-fixed-dose-combination-of-insulin-degludec-and-liraglutide-xultophy-100-3-6-for-the-treatment-of-type-2-diabetes
#20
Kira Harris, Kimberly Lovin Nealy
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations...
August 1, 2017: Annals of Pharmacotherapy
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