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Clinical pharmacology

Oriane Blanquie, Frank Bradke
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone...
March 12, 2018: Current Opinion in Neurobiology
Alejandro Amor-Coarasa, James Kelly, Shashikanth Ponnala, Yogindra Vedvyas, Anastasia Nikolopoulou, Clarence Williams, Moonsoo M Jin, J David Warren, John W Babich
INTRODUCTION: CXCR4 specific [18 F]-labeled positron emission tomography (PET) imaging agents are needed which would enable general distribution of the radiotracer for clinical investigation. We sought to synthesize, radiolabel and evaluate [18 F]RPS-544, a novel non-peptide CXCR4 antagonist as a CXCR4 specific probe. We compared [18 F]RPS-544 with the previously published [18 F]-3 ([18 F]RPS-510 in this paper) in a bi-lateral tumor model of differential CXCR4 expression for its ability to selectively target CXCR4 expression...
January 31, 2018: Nuclear Medicine and Biology
Kateřina Štulíková, Marcel Karabín, Jakub Nešpor, Pavel Dostálek
Hop ( Humulus lupulus L.), as a key ingredient for beer brewing, is also a source of many biologically active molecules. A notable compound, 8-prenylnaringenin (8-PN), structurally belonging to the group of prenylated flavonoids, was shown to be a potent phytoestrogen, and thus, became the topic of active research. Here, we overview the pharmacological properties of 8-PN and its therapeutic opportunities. Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and post-menopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women...
March 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mariana Matias, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
Purpose - During the discovery and development of new drugs, compounds with low aqueous solubility pose special challenges in their pharmacological evaluation and, therefore, the selection of appropriate vehicles to administer the compounds of interest is determinant for the quality of the results generated during the in vivo non-clinical studies. This work aimed to evaluate the motor deficit (as a surrogate of neurotoxicity) of several administration/delivery vehicles through the rotarod performance test. Methods - Trained male CD-1 mice were intraperitoneally administered with the following vehicles: dimethyl sulfoxide (DMSO), aqueous sodium chloride (NaCl) 0...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Behjat Javadi
Cancer is the second leading cause of death with profound socio-economic consequences worldwide. Growing evidence suggests the crucial role of diet on cancer prevention and treatment. In Traditional Persian Medicine (TPM) there is a major focus on contribution of special diet and foods to cancer management. In the present article, the cytotoxic and antitumor activities of several food items including plants and animal products recommended by TPM as anticancer agents are discussed. Strong evidence supports the anticancer effects of beetroot (Beta vulgris) and its major compound betanin, cinnamon and cinnamaldehyde, barley (H...
March 15, 2018: Nutrition and Cancer
Lone Baandrup, Bjørn H Ebdrup, Jesper Ø Rasmussen, Jane Lindschou, Christian Gluud, Birte Y Glenthøj
BACKGROUND: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. OBJECTIVES: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use...
March 15, 2018: Cochrane Database of Systematic Reviews
Akhil Kumar, Ashish Tiwari, Ashok Sharma
Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target...
March 15, 2018: Current Neuropharmacology
Jasveen J Kandhai-Ragunath, Carine J M Doggen, Liefke C van der Heijden, Marlies M Kok, Paolo Zocca, Bjorn de Wagenaar, Cees Doelman, Harald T Jørstad, Ron J G Peters, Clemens von Birgelen
Knowledge about the changes in endothelial function after ST-elevation myocardial infarction (STEMI) is of substantial interest, but serial data are scarce. The aim of the present study was to noninvasively evaluate whether endothelial function, as assessed shortly after primary percutaneous coronary intervention (PPCI) for STEMI, may improve until 12-month follow-up. This prospective observational cohort study was performed in patients in the RESPONSE randomized trial who participated in a substudy and underwent noninvasive assessment of endothelial function at 1 (baseline), 6, and 12-month follow-up after treatment of a STEMI by PPCI...
March 14, 2018: Heart and Vessels
Dominik Linz, R Doug McEvoy, Martin R Cowie, Virend K Somers, Stanley Nattel, Patrick Lévy, Jonathan M Kalman, Prashanthan Sanders
Importance: Obstructive sleep apnea (OSA) is the most common clinically significant breathing abnormality during sleep. It is highly prevalent among patients with atrial fibrillation (AF), and it promotes arrhythmogenesis and impairs treatment efficacy. Observations: The prevalence of OSA ranges from 3% to 49% in population-based studies and from 21% to 74% in patients with AF. Diagnosis and treatment of OSA in patients with AF requires a close interdisciplinary collaboration between electrophysiologists, cardiologists, and sleep specialists...
March 14, 2018: JAMA Cardiology
Beatriz Silva Lima, Mafalda Ascensão Videira
Since the human genome decoding, understanding and identification of genetic disturbances behind many diseases, including cancer, are intensively increasing. Scientific and technological advances in this area trigger the search for therapeutic (curative) approaches targeting the correction of gene disturbances. Gene therapy medicinal products (GTMPs) emerge in this context, bringing new challenges for their characterization. Compared to small molecules, biodistribution is fundamental to identifying target organs and anticipating safety and efficacy, may be integrated into safety and pharmacology studies, and may eventually be anticipated based on specificities of vectors and constructs...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Li-Chan Yang, Jiunn-Wang Liao, Chi-Luan Wen, Wen-Chuan Lin
Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu) that was developed by crossbreeding D. tosaense and D. nobile . Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE) in male and female Sprague-Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Pratima Murthy
While guidelines for psychosocial interventions in addictive disorders in India were earlier rooted in clinical experience and global empirical evidence, recently there have been efforts to develop guidelines for intervention based on the local needs assessments of specific populations and more appreciably, a testing of the effectiveness of the interventions. This supplement on psychosocial interventions for addictive disorders covers some of the important aspects of psychosocial interventions in five sections...
February 2018: Indian Journal of Psychiatry
Arnaud Boyer, Eddy Pasquier, Pascale Tomasini, Joseph Ciccolini, Laurent Greillier, Nicolas Andre, Fabrice Barlesi, Celine Mascaux
Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Qianjin Li, Omar Awad Alsaidan, Yongjie Ma, Sungjin Kim, Junchen Liu, Thomas Albers, Kebin Liu, Zanna Beharry, Shaying Zhao, Fen Wang, Iryna Lebedyeva, Houjian Cai
Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling facilitates tumor initiation and progression. Although currently approved inhibitors of FGFR kinase have shown therapeutic benefit in clinical trials, over-expression or mutations of FGFRs eventually confer drug resistance and thereby abrogate the desired activity of kinase inhibitors in many cancer types. In this study, we report that loss of myristoylation of fibroblast growth factor receptor substrate 2 (FRS2α), a scaffold protein essential for FGFR signaling, inhibits FGF/FGFR-mediated oncogenic signaling and FGF10-induced tumorigenesis...
March 14, 2018: Journal of Biological Chemistry
Gin S Malhi, Tim Outhred, Grace Morris, Philip M Boyce, Richard Bryant, Paul B Fitzgerald, Malcolm J Hopwood, Bill Lyndon, Roger Mulder, Greg Murray, Richard J Porter, Ajeet B Singh, Kristina Fritz
In December 2015, the Royal Australian and New Zealand College of Psychiatrists published a comprehensive set of mood disorder clinical practice guidelines for psychiatrists, psychologists and mental health professionals. This guideline summary, directed broadly at primary care physicians, is an abridged version that focuses on bipolar disorder. It is intended as an aid to the management of this complex disorder for primary care physicians working in collaboration with psychiatrists to implement successful long term management...
March 19, 2018: Medical Journal of Australia
Alejo Rodriguez-Vida, Joaquim Bellmunt
Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years. Similarly, before the advent of the immune checkpoint inhibitors, there were no FDA-approved drugs for second-line therapy. In the last few years, impressive signs of anti-tumor activity have been reported with several immunotherapy agents targeting the programmed cell death-1 (PD-1) pathway...
March 14, 2018: Expert Review of Anticancer Therapy
Leandro Nóbrega, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U...
March 14, 2018: Drug Metabolism Reviews
Nitin Agarwal, Georgios A Zenonos, Prateek Agarwal, Frank J Walch, Eileen Roach, Sandra J Stokes, Robert M Friedlander, Peter C Gerszten
BACKGROUND: Pharmacological prophylaxis for venous thromboembolism (VTE) in the neurosurgical population is still a matter of debate, as the risk-to-benefit ratio is not well defined. OBJECTIVE: To further evaluate the risk-to-benefit ratio of VTE prophylaxis (VTEP) for all neurosurgical procedures. METHODS: A prospective evaluation was performed after the initiation of a VTEP protocol for 11 436 patients undergoing neurosurgical procedures over 24 mo...
March 9, 2018: Neurosurgery
Cordula Netzer, Pascal Distel, Uwe Wolfram, Hans Deyhle, Gregory F Jost, Stefan Schären, Jeroen Geurts
Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments...
March 14, 2018: International Journal of Molecular Sciences
Edmund Burke, Sanjeev A Datar
PURPOSE OF REVIEW: The essential role of the lymphatic system in fluid homeostasis, nutrient transport, and immune trafficking is well recognized; however, there is limited understanding of the mechanisms that regulate lymphatic function, particularly in the setting of critical illness. The lymphatics likely affect disease severity and progression in every condition, from severe systemic inflammatory states to respiratory failure. Here, we review structural and functional disorders of the lymphatic system, both congenital and acquired, as they relate to care of the pediatric patient in the intensive care setting, including novel areas of research into medical and procedural therapeutic interventions...
March 13, 2018: Current Opinion in Pediatrics
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