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https://www.readbyqxmd.com/read/28334734/multinucleated-polyploidy-drives-resistance-to-docetaxel-chemotherapy-in-prostate-cancer
#1
Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28332171/sport-and-male-sexuality
#2
REVIEW
P Sgrò, L Di Luigi
The relationships between sport and sexuality in males are of great social and clinical interest, because of sports and motor activities that highly promote social and sexual relationships. Even if few literature exist, two main questions should be taken into account: whether and how physical exercise and sport positively or negatively influence sexual health and behavior and/or whether and how sexual behavior may affect a sub-sequent sport performance. Physical exercise and sport per se can influence, positively or negatively, the hypothalamic-pituitary-testicular axis function and, consequently, the individual's reproductive and/or sexual health...
March 22, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28330413/molecular-dynamic-simulation-and-dft-study-on-the-drug-dna-interaction-crocetin-as-an-anticancer-and-dna-nanostructure-model
#3
Ebrahim Azarhazin, Mohammad Izadyar, Mohammad Reza Housaindokht
In this research, the interaction of Crocetin as an anticancer drug and a Dickerson DNA has been investigated. 25 ns molecular dynamic simulations of Crocetin and DNA composed of twelve base pairs and a sequence of d(CGCGAATTCGCG)2 were done in water. Three definite parts of the B-DNA were considered in analyzing the best interactive site from the thermodynamic point of view. Binding energy analysis showed that van der Waals interaction is the most important part related to the reciprocal O and H atoms of the Crocetin and DNA...
March 22, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28325553/metabolomics-through-the-lens-of-precision-cardiovascular-medicine
#4
REVIEW
Sin Man Lam, Yuan Wang, Bowen Li, Jie Du, Guanghou Shui
Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development...
March 8, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28325042/enhanced-endosomal-escape-by-light-fueled-liquid-metal-transformer
#5
Yue Lu, Yiliang Lin, Zhaowei Chen, Quanyin Hu, Yang Liu, Shuangjiang Yu, Wei Gao, Michael D Dickey, Zhen Gu
Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal...
March 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/28324483/the-contribution-of-drug-overdose-to-educational-gradients-in-life-expectancy-in-the-united-states-1992-2011
#6
Jessica Y Ho
Since the mid-1990s, the United States has witnessed a dramatic rise in drug overdose mortality. Educational gradients in life expectancy widened over the same period, and drug overdose likely plays a role in this widening, particularly for non-Hispanic whites. The contemporary drug epidemic is distinctive in terms of its scope, the nature of the substances involved, and its geographic patterning, which influence how it impacts different education groups. I use vital statistics and National Health Interview Survey data to examine the contribution of drug overdose to educational gradients in life expectancy from 1992-2011...
March 21, 2017: Demography
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#7
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28322750/supradural-inflammatory-soup-in-awake-and-freely-moving-rats-induces-facial-allodynia-that-is-blocked-by-putative-immune-modulators
#8
Julie Wieseler, Amanda Ellis, Andrew McFadden, Kendra Stone, Kimberley Brown, Sara Cady, Leandro F Bastos, David Sprunger, Niloofar Rezvani, Kirk Johnson, Kenner C Rice, Steven F Maier, Linda R Watkins
Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown...
March 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28321145/drug-pricing-transparency-the-new-retail-revolution
#9
Kaitlyn N Dana, John B Hertig, Robert J Weber
As spending on medications in the United States increases with each passing year, the need for drug pricing transparency by manufacturers also increases. Drug spending, excluding rebates and discounts, was $309.5 billion in 2015, up 8.5% from 2014. Drug pricing transparency has been a topic of debate across the health care system. This column reviews the issue of drug pricing and emphasizes the need for transparency in this area. We will discuss factors that influence drug pricing, policies and ways to reduce the rising costs of drugs, and the role of pharmacy leaders in managing this problem...
February 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28321135/ismp-adverse-drug-reactions
#10
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
February 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28318251/molecular-simulation-studies-on-the-binding-selectivity-of-type-i-inhibitors-in-the-complexes-with-ros1-versus-alk
#11
Yuanxin Tian, Yonghuan Yu, Yudong Shen, Hua Wan, Shan Chang, Tingting Zhang, Shanhe Wan, Jiajie Zhang
ROS1 and ALK are promising targets of anti-cancer drugs for non small cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, selective ROS1 inhibitor is relative rarely. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear...
March 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28317210/epidemiology-of-hiv-and-hepatitis-c-infection-among-women-who-inject-drugs-in-northeast-india-a-respondent-driven-sampling-study
#12
Allison M Mcfall, Sunil S Solomon, Greg M Lucas, David D Celentano, Aylur K Srikrishnan, Muniratnam S Kumar, Shruti H Mehta
BACKGROUND AND AIMS: Despite extensive research on HIV and hepatitis C (HCV) among people who inject drugs (PWID), there remains a gap in knowledge on the burden among women who inject drugs and their unique contexts and risk factors. This analysis compares HIV and HCV prevalence in female and male PWID and estimates injection and sexual risk correlates of prevalent HIV and HCV infection among women in Northeast India. DESIGN: Cross-sectional sample accrued using respondent-driven sampling...
March 20, 2017: Addiction
https://www.readbyqxmd.com/read/28316031/transactivation-domain-of-human-c-myc-is-essential-to-alleviate-poly-q-mediated-neurotoxicity-in-drosophila-disease-models
#13
Kritika Raj, Surajit Sarkar
Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis...
March 18, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28316026/zebrafish-as-a-model-to-evaluate-peptide-related-cancer-therapies
#14
REVIEW
Austin Y Shull, Chien-An A Hu, Yong Teng
Peptide-derived drug discovery has experienced a remarkable resurgence in the past decade since the failure of small-molecule modulators to effectively access the large binding surfaces of intracellular protein-protein interactions as well as "undruggable" residues of certain disease-driving proteins. However, the effectiveness of peptide-based cancer therapies is being questioned in light of declines in pharmaceutical R&D efficiency. As a model of whole organism, zebrafish provide a means to develop promising peptide and protein anticancer agents in an informative, cost-effective and time-efficient manner, which also allows for surveying mechanisms of drug action and optimization of drug delivery system...
March 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28315500/relation-between-sexual-dysfunctions-and-epilepsy-type-of-epilepsy-type-of-antiepileptic-drugs-a-prospective-study
#15
Carlo Pavone, Ninfa Giacalone, Lidia Urso, Leila Zummo, Brigida Fierro
INTRODUCTION: The aim of this study was to evaluate the incidence of sexual dysfunctions in males with epilepsy, the type of epilepsy, the frequency of seizures, the type of antiepileptic drugs (AEDs), the serum hormonal profile and the presence of psychiatric comorbidity. METHODS: Sixty-one patients focused on type of epilepsy, frequency of seizures, AEDs, hormonal profile and presence of mood disorders. We excluded all patients with severe neurologic and psychiatric impairment and patient who were not able to fill questionnaires...
March 18, 2017: Urologia
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#16
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28304309/mouse-models-of-alzheimer-s-disease
#17
Gisela Esquerda-Canals, Laia Montoliu-Gaya, Jofre Güell-Bosch, Sandra Villegas
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28304215/use-of-statistical-and-pharmacokinetic-pharmacodynamic-modeling-and-simulation-to-improve-decision-making-a-section-summary-report-of-the-trends-and-innovations-in-clinical-trial-statistics-conference
#18
Holly Kimko, Seth Berry, Michael O'Kelly, Nitin Mehrotra, Matthew Hutmacher, Venkat Sethuraman
The application of modeling and simulation (M&S) methods to improve decision-making was discussed during the Trends & Innovations in Clinical Trial Statistics Conference held in Durham, North Carolina, USA on May 1-4, 2016. Uses of both pharmacometric and statistical M&S were presented during the conference, highlighting the diversity of the methods employed by pharmacometricians and statisticians to address a broad range of quantitative issues in drug development. Five presentations are summarized herein, which cover the development strategy of employing M&S to drive decision-making; European initiatives on best practice in M&S; case studies of pharmacokinetic/pharmacodynamics modeling in regulatory decisions; estimation of exposure-response relationships in the presence of confounding; and the utility of estimating the probability of a correct decision for dose selection when prior information is limited...
February 7, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28302862/arresting-the-development-of-addiction-the-role-of-%C3%AE-arrestin2-in-drug-abuse
#19
Kirsten A Porter-Stransky, David Weinshenker
The protein β-arrestin2 (βarr2) directly interacts with receptors and signaling pathways that mediate the behavioral effects of drugs of abuse, making it a prime candidate for therapeutic interventions. βarr2 drives desensitization and internalization of G protein-coupled receptors, including dopamine, opioid, and cannabinoid receptors, and can also trigger G protein-independent intracellular signaling. βarr2 mediates several drug-induced behaviors, but the relationship is complex and dependent on the type of behavior (e...
March 16, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28302825/waste-disposal-an-attractive-strategy-for-cancer-therapy
#20
REVIEW
Jemilat Salami, Craig M Crews
Targeted therapies for cancer are typically small molecules or monoclonal antibodies that act by inhibiting the activity of specific proteins that drive tumor growth. Although many of these drugs are effective in cancer patients, the response is often not durable because tumor cells develop resistance to the drugs. Another limitation of this strategy is that not all oncogenic driver proteins are "druggable" enzymes or receptors with activities that can be inhibited. Here we describe an alternative approach to targeted therapy that is based on co-opting the cellular quality-control machinery-the ubiquitin-proteasome system-to remove specific cancer-causing proteins from the cell...
March 17, 2017: Science
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