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Clinical pharmacology

Constanze Hantel, Igor Shapiro, Giada Poli, Costanza Chiapponi, Martin Bidlingmaier, Martin Reincke, Michaela Luconi, Sara Jung, Felix Beuschlein
In recent years it has been recognized that clinical translation of novel therapeutic strategies for patients with adrenocortical carcinoma (ACC) often fails. These disappointing results indicate that the currently utilized tumor models only poorly reflect relevant pathophysiology and, thereby, do not predict clinical applicability of novel pharmacological approaches. However, also the development of new preclinical ACC models has remained a challenge with only one human cell line (NCI-H295R) and one recently established human pediatric xenograft model (SJ-ACC3) being available for this highly heterogeneous malignancy...
October 15, 2016: Oncotarget
Steffen T Simon, Irene J Higginson, Sara Booth, Richard Harding, Vera Weingärtner, Claudia Bausewein
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2010, on 'Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults'. Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non-malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. At the time of the previously published Cochrane review, there was no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in people with advanced cancer and chronic obstructive pulmonary disease (COPD)...
October 20, 2016: Cochrane Database of Systematic Reviews
Sofian Berrouiguet, Maria Luisa Barrigón, Sara A Brandt, Santiago Ovejero-García, Raquel Álvarez-García, Juan Jose Carballo, Philippe Lenca, Philippe Courtet, Enrique Baca-García
PURPOSE: The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. METHOD: A web application ( was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014...
2016: PloS One
Lukasz Krokowicz, Adam Bobkiewicz, Maciej Borejsza-Wysocki, Barbara Kuczynska, Aleksandra Lisowska, Urszula Skowronska-Piekarska, Jacek Paszkowski, Jaroslaw Walkowiak, Michal Drews, Tomasz Banasiewicz
The term constipation with regard to patients with a stoma is defined as impaired bowel movements associated with increased stool consistency or long periods without bowel movements that lead to discomfort, flatulence, and abdominal pain. Information about constipation in patients with a stoma is limited. A prospective, descriptive study was conducted among patients attending ostomy and proctology outpatient clinics in Poznan, Poland between January 2011 and December 2014 to assess the role of dietary and pharmacological strategies in the management of constipation in patients with a stoma...
December 2015: Ostomy/wound Management
Elisa Bruno, Alessandra Nicoletti, Graziella Quattrocchi, Graziella Filippini, Carlo Colosimo, Mario Zappia
BACKGROUND: Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are well-established treatments in clinical practice, they may be ineffective in 25% to 55% of patients and can produce serious adverse events in a large percentage of them. For these reasons, it is worth evaluating the treatment alternatives for essential tremor. Some specialists have suggested that pregabalin could be a potentially useful agent, but there is uncertainty about its efficacy and safety...
October 20, 2016: Cochrane Database of Systematic Reviews
Helen Louise Adams, Dharamveer Basude, Alison Kyle, Sarah Sandmann, Siba Prosad Paul
Irritable bowel syndrome (IBS) is the most common cause of non-organic recurrent abdominal pain in children. IBS is a clinical diagnosis, which is based on the Rome IV criteria for functional gastrointestinal disorders in children, as well as the patient's history. The diagnosis of IBS is established following the exclusion of organic causes of recurrent abdominal pain. Staggered investigations should be avoided because they might increase the child's and family's anxiety in the absence of an organic diagnosis...
October 12, 2016: Nursing Standard
Shobhit Srivastava, Anil K Saksena, Sanjay Khattri, Santosh Kumar, Raghubendra Singh Dagur
BACKGROUND AND PURPOSE: Curcuma longa L. (CL), an Indian herb, has been used to treat many disorders because of its wide spectrum of pharmacological activities. It has been shown to exhibit anti-oxidant and anti-inflammatory properties, and is being used as herbal remedy since ancient times. Osteoarthritis of knee (KOA) is a chronic painful disorder in which prolong use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids may result into many serious side effects; hence, there is a need to develop herbal drugs, having good analgesia without side effects...
October 19, 2016: Inflammopharmacology
V R Knight-Schrijver, V Chelliah, L Cucurull-Sanchez, N Le Novère
Recent growth in annual new therapeutic entity (NTE) approvals by the U.S. Food and Drug Administration (FDA) suggests a positive trend in current research and development (R&D) output. Prior to this, the cost of each NTE was considered to be rising exponentially, with compound failure occurring mainly in clinical phases. Quantitative systems pharmacology (QSP) modelling, as an additional tool in the drug discovery arsenal, aims to further reduce NTE costs and improve drug development success. Through in silico mathematical modelling, QSP can simulate drug activity as perturbations in biological systems and thus understand the fundamental interactions which drive disease pathology, compound pharmacology and patient response...
2016: Computational and Structural Biotechnology Journal
Hao Huang, Linfu Li, Weimei Shi, Hai Liu, Jianqiong Yang, Xiaoliang Yuan, Longhuo Wu
Nobiletin (NOB) chemically known as 5,6,7,8,3',4'-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca(2+)/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
J Hefner, H Csef
The last ten years have seen hardly any improvement in the prognosis of ovarian carcinoma. There is a great need for new treatment strategies, and a recent retrospective study showing a survival advantage with the use of beta blockers met with a very positive response. This systematic review summarizes the current state of knowledge and research on the topic: A database analysis identified six clinical studies showing inconsistent results with respect to the administration of beta blockers and disease course...
October 2016: Geburtshilfe und Frauenheilkunde
Robyn T Rebbeck, Maram M Essawy, Florentin R Nitu, Benjamin D Grant, Gregory D Gillispie, David D Thomas, Donald M Bers, Razvan L Cornea
Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca(2+) channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca(2+) regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca(2+)], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders...
October 19, 2016: Journal of Biomolecular Screening
Connie M Rhee, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction...
October 20, 2016: Nephron
Konstantinos Tzelepis, Hiroko Koike-Yusa, Etienne De Braekeleer, Yilong Li, Emmanouil Metzakopian, Oliver M Dovey, Annalisa Mupo, Vera Grinkevich, Meng Li, Milena Mazan, Malgorzata Gozdecka, Shuhei Ohnishi, Jonathan Cooper, Miten Patel, Thomas McKerrell, Bin Chen, Ana Filipa Domingues, Paolo Gallipoli, Sarah Teichmann, Hannes Ponstingl, Ultan McDermott, Julio Saez-Rodriguez, Brian J P Huntly, Francesco Iorio, Cristina Pina, George S Vassiliou, Kosuke Yusa
Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates...
October 18, 2016: Cell Reports
Mengmeng Wang, Amanda K Kussrow, Mireia Fernandez Ocana, Jeffrey R Chabot, Christopher S Lepsy, Darryl J Bornhop, Denise M O'Hara
BACKGROUND AND PURPOSE: A monoclonal antibody (PF-00547659) against Mucosal Adressin Cell Adhesion Molecule (MAdCAM), expressed as both soluble (sMAdCAM) and trans-membrane (mMAdCAM) target forms, showed over 30-fold difference in antibody-target KD between in vitro (Biacore) and clinically derived (KD,in-vivo ) values. Back-scattering interferometry (BSI) was applied to acquire physiologically relevant KD values which were used to establish in vitro and in vivo correlation (IVIVC). EXPERIMENTAL APPROACH: Back-scattering interferometry (BSI) was applied to obtain KD values between PF-00547659 and recombinant human MAdCAM in buffer or CHO cells and endogenous MAdCAM in human serum or colon tissue...
October 19, 2016: British Journal of Pharmacology
Rosemary Fama, Edith V Sullivan, Stephanie A Sassoon, Adolf Pfefferbaum, Natalie M Zahr
BACKGROUND: Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. METHODS: HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory...
October 19, 2016: Alcoholism, Clinical and Experimental Research
Fatma Yildirim, Filiz Sadi Aykan
We read the report by Çeltikçi et al in the Turkish Neurosurgery with great interest. In this single-center retrospective study, they analysed 449 intracranial meningioma patients underwent open surgery. They stated that venous thromboembolism (VTE) had been seen in 21 (4.6%) of their patients. This is an important issue because VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the most common overall complication in meningioma surgery and is fatal in up to one third of patients (2)...
September 26, 2016: Turkish Neurosurgery
Gino A Vena, Maria Concetta Fargnoli, Nicoletta Cassano, Giuseppe Argenziano
The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown. Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications. Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Meiou Dai, Chenjing Zhang, Ayad Ali, Xinyuan Hong, Jun Tian, Chieh Lo, Nadège Fils-Aimé, Sergio A Burgos, Suhad Ali, Jean-Jacques Lebrun
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients...
October 19, 2016: Scientific Reports
C Michael White, Elaine Nguyen
OBJECTIVE: To review the limitations of current antiarrhythmic drugs in atrial fibrillation (AF) and discuss the rationale and clinical trials supporting the use of ranolazine in AF. DATA SOURCES: MEDLINE was searched from 1980 to September 2016 using the terms ranolazine, atrial fibrillation, coronary artery bypass grafting, and valve surgery STUDY SELECTION AND DATA EXTRACTION: English-language studies and reviews assessing antiarrhythmic drugs, including ranolazine, were incorporated...
October 6, 2016: Annals of Pharmacotherapy
Huai-Peng Lin, Zhou-Li Cheng, Ruo-Yu He, Lei Song, Meng-Xin Tian, Lisha Zhou, Beezly S Groh, Weiren Liu, Min-Biao Ji, Chen Ding, Ying-Hong Shi, Kun-Liang Guan, Dan Ye, Yue Xiong
Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacological inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity and other diseases. Here we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin-ligase TRIM21...
October 10, 2016: Cancer Research
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