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https://www.readbyqxmd.com/read/28811228/curcumin-in-alzheimer-s-disease-can-we-think-to-new-strategies-and-perspectives-for-this-molecule
#1
REVIEW
Serafini Melania Maria, Catanzaro Michele, Rosini Michela, Racchi Marco, Lanni Cristina
Population aging is an irreversible global trend with economic and socio-political consequences. One of the most invalidating outcomes of aging in the elderly is cognitive decline, leading to dementia and often related to neurodegenerative disorders. Among these latter, Alzheimer's disease (AD) is the major cause of dementia, affecting more than 30 million of individuals worldwide. To date, the treatment of AD remains a challenge because of an incomplete understanding of the events that lead to the selective neurodegeneration typical of Alzheimer's brains...
August 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28811184/experimental-cocrystal-screening-and-solution-based-scale-up-cocrystallization-methods
#2
REVIEW
Maria Malamatari, Steven A Ross, Dennis Douroumis, Sitaram P Velaga
Cocrystals are crystalline single phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates nor simple salts. If one of the components is an active pharmaceutical ingredient (API), the term pharmaceutical cocrystal is often used. There is a growing interest among drug development scientists in exploring cocrystals, as means to address physicochemical, biopharmaceutical and mechanical properties and expand solid form diversity of the API...
August 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28811111/cell-cultures-in-drug-discovery-and-development-the-need-of-reliable-in-vitro-in-vivo-extrapolation-for-pharmacodynamics-and-pharmacokinetics-assessment
#3
REVIEW
Karol Jaroch, Alina Jaroch, Barbara Bojko
For ethical and cost-related reasons, use of animals for the assessment of mode of action, metabolism and/or toxicity of new drug candidates has been increasingly scrutinized in research and industrial applications. Implementation of the 3 "Rs"(1); rule (Reduction, Replacement, Refinement) through development of in silico or in vitro assays has become an essential element of risk assessment. Physiologically based pharmacokinetic (PBPK(2)) modeling is the most potent in silico tool used for extrapolation of pharmacokinetic parameters to animal or human models from results obtained in vitro...
July 27, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28810125/cheminformatic-analysis-of-anti-malarial-chemical-space-illuminates-therapeutic-mechanisms-and-offers-strategies-for-therapy-development
#4
Julia Nogueira Varela, María Fernanda Fernanda Lammoglia Cobo, Sandip V Pawar, Vikramaditya G Yadav
The clear and present danger of malaria, which has been amplified in recent years by climate change, and the progressive thinning of our drug arsenal over the past two decades raise uncomfortable questions about the current state and future of anti-malarial drug development. Besides suffering from many of the same technical challenges that affect drug development in other disease areas, the quest for new anti-malarial therapies is also hindered by the complex, dynamic life cycle of the malaria parasite, P. falciparum, in its mosquito and human hosts, and its role thereof in the elicitation of drug resistance...
August 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28810082/therapeutic-monoclonal-antibodies-and-clinical-laboratory-tests-when-why-and-what-is-expected
#5
Zhanhu Zhang, Wenjie Hu, Linlin Li, Hongxia Ding, Haibo Li
BACKGROUND: We herein provide an overview of the clinical laboratory tests that should be performed before, during and after using therapeutic monoclonal antibodies (mAbs) and the clinical laboratory tests that may be affected by mAbs. METHODS: The labels of FDA-approved therapeutic mAbs were downloaded from DailyMed (the official website for drug labels) and were used as the sources of data for this review. RESULTS: It was found that most of the labels provided information relevant to the clinical laboratory tests, including the tests needed before mAbs treatment to check the patients' background status and to identify potentially sensitive patients, the tests needed during or after the treatment to evaluate the patients' response, and the mAbs that may lead to false positive or negative results for clinical laboratory tests...
August 15, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28807365/-the-breakthrough-of-personalized-medicine-new-hopes-and-new-challenges
#6
REVIEW
Ronan Flippot, Christophe Massard, Edouard Auclin, David Azria, Héloïse Bourien, Philippe Rochigneux, Antoine Schernberg, Loïc Verlingue, Lara Zafrani, Stéphane Vignot
The development of personalized medicine in oncology is based on biomarkers that help select populations for more efficient and less toxic therapies. The onset of molecular biology led to new paradigms in drug development, with efficacy data reported in early clinical trials and accelerated approvals. Multiple clinical trials, including SHIVA, SAFIR-01 and MOSCATO-01, have been developed to evaluate the interest of treatment decision-making based on tumor molecular profiling, with the ambition to replace historical clinical and pathological classifications...
August 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28807165/effect-and-mechanism-of-chinese-herbal-medicine-on-parkinson-s-disease
#7
Bai-Yun Zeng
Parkinson's disease is a progressive neurodegenerative disorder. Although both genetic and environmental factors are implicated in the development of Parkinson's disease, the cause of the disease is still unclear. So far conventional treatments to Parkinson's are symptomatic relief and focused mainly on motor symptoms. Chinese herbal medicine has been used to treat many conditions in China, Korea, Japan, and many Southeast Asian countries for 1000 years. During past a few decades, Chinese herbal medicine has gained wider and increasing acceptance within both public and medical profession due to its effectiveness on many conditions in western countries...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28806989/maximising-value-from-a-united-kingdom-biomedical-research-centre-study-protocol
#8
Trisha Greenhalgh, Pavel V Ovseiko, Nick Fahy, Sara Shaw, Polly Kerr, Alexander D Rushforth, Keith M Channon, Vasiliki Kiparoglou
BACKGROUND: Biomedical Research Centres (BRCs) are partnerships between healthcare organisations and universities in England. Their mission is to generate novel treatments, technologies, diagnostics and other interventions that increase the country's international competitiveness, to rapidly translate these innovations into benefits for patients, and to improve efficiency and reduce waste in healthcare. As NIHR Oxford BRC (Oxford BRC) enters its third 5-year funding period, we seek to (1) apply the evidence base on how best to support the various partnerships in this large, multi-stakeholder research system and (2) research how these partnerships play out in a new, ambitious programme of translational research...
August 14, 2017: Health Research Policy and Systems
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
#9
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/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#10
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28805581/nonmotor-parkinson-s-and-future-directions
#11
Nataliya Titova, K Ray Chaudhuri
Nonmotor symptoms (NMS) of Parkinson's disease (PD) are integral to the condition largely regarded as a motor syndrome. A range of NMS underpin the prodromal stage of Parkinson's and are present with variable frequency, range, and nature across the whole journey of a patient with Parkinson's from the onset of the motor disease to palliative stage. These symptoms also are key determinants of quality of life of the patient as well as the carer. Despite this, recognition management and focused treatment of NMS of PD remain poor...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805446/epigallocatechin-gallate-as-an-anti-obesity-therapeutic-compound-an-in-silico-approach-for-structure-based-drug-designing
#12
Muhammad Shahid Javaid, Noreen Latief, Bushra Ijaz, Usman Ali Ashfaq
Epigallocatechin gallate is a polyphenol of tea plants. Other than tea its trace amounts are found in apple skin, onions and plums. It has anti-adipogenic and anti-oxidant potential. It was investigated that epigallocatechin gallate stopped the adipogenic differentiation of mice mesenchymal stem cells but its underlying mechanism is not well understood. Different proteins and transcription factors responsible for differentiation of adipocytes could be its targets. This study was designed to determine the potential target of epigallocatechin gallate in human...
August 14, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28804913/on-bh3-mimetics-and-ca-2-signaling
#13
Pawel E Ferdek, Monika A Jakubowska
Preclinical Research BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl-2 family proteins. Just like the BH3-only proteins, these compounds bind to the hydrophobic cleft of the pro-survival Bcl-2 members such as Bcl-2 or Bcl-xL, and disrupt their heterodimerization with pro-apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, it has become clear that Bcl-2 family proteins are engaged in regulation of intracellular Ca(2+) homeostasis, including Ca(2+) release from the intracellular stores as well as Ca(2+) fluxes across the plasma membrane...
August 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28804696/neonatal-safety-information-reported-to-the-fda-during-drug-development-studies
#14
Debbie Avant, Gerri Baer, Jason Moore, Panli Zheng, Alfred Sorbello, Ron Ariagno, Lynne Yao, Gilbert J Burckart, Jian Wang
BACKGROUND: Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015...
2017: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/28803390/cancer-clonal-theory-immune-escape-and-their-evolving-roles-in-cancer-multi-agent-therapeutics
#15
REVIEW
Jonathan L Messerschmidt, Prianka Bhattacharya, Gerald L Messerschmidt
PURPOSE OF REVIEW: The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus...
August 12, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28801574/intestinal-transepithelial-permeability-of-oxytocin-into-the-blood-is-dependent-on-the-receptor-for-advanced-glycation-end-products-in-mice
#16
Haruhiro Higashida, Kazumi Furuhara, Agnes-Mikiko Yamauchi, Kisaburo Deguchi, Ai Harashima, Seiichi Munesue, Olga Lopatina, Maria Gerasimenko, Alla B Salmina, Jia-Sheng Zhang, Hikari Kodama, Hironori Kuroda, Chiharu Tsuji, Satoshi Suto, Hiroshi Yamamoto, Yasuhiko Yamamoto
Plasma oxytocin (OT) originates from secretion from the pituitary gland into the circulation and from absorption of OT in mother's milk into the blood via intestinal permeability. However, the molecular mechanism underlying the absorption of OT remains unclear. Here, we report that plasma OT concentrations increased within 10 min after oral delivery in postnatal day 1-7 mice. However, in Receptors for Advanced Glycation End Products (RAGE) knockout mice after postnatal day 3, an identical OT increase was not observed...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801207/crediblemeds-org-what-does-it-offer
#17
REVIEW
Raymond L Woosley, Kristin Black, C William Heise, Klaus Romero
Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds...
August 1, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28801024/understanding-the-role-of-socs-signaling-in-neurodegenerative-diseases-current-and-emerging-concepts
#18
REVIEW
Antonia Cianciulli, Rosa Calvello, Chiara Porro, Teresa Trotta, Maria Antonietta Panaro
Suppressor of cytokine signaling proteins (SOCS) are a family of intracellular cytokine inducible proteins, consisting of eight members. They are involved in the complex control of the inflammatory response through their actions on various signaling pathways, including the JAK/STAT and NF-κB pathways. A series of studies has shown that SOCS proteins are involved in the regulation and progression of immune responses in microglia cells. The accumulated data suggest that modulation of SOCS expression could be a target for drug development aimed at controlling inflammation in the brain...
August 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#19
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/28798317/sphingomyelin-as-a-myelin-biomarker-in-csf-of-acquired-demyelinating-neuropathies
#20
Giovanna Capodivento, Davide Visigalli, Martina Garnero, Roberto Fancellu, Michela Demetra Ferrara, Abdul Basit, Zeeshan Hamid, Vito Paolo Pastore, Silvano Garibaldi, Andrea Armirotti, Gianluigi Mancardi, Carlo Serrati, Elisabetta Capello, Angelo Schenone, Lucilla Nobbio
Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. We found that SM levels mirror both peripheral myelination during development and small myelin rearrangements in experimental models. As in acquired demyelinating peripheral neuropathies myelin breakdown occurs, SM amount in the CSF of these patients might detect the myelin loss...
August 10, 2017: Scientific Reports
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