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https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#1
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088032/oral-cannabidiol-does-not-produce-a-signal-for-abuse-liability-in-frequent-marijuana-smokers
#2
Shanna Babalonis, Margaret Haney, Robert J Malcolm, Michelle R Lofwall, Victoria R Votaw, Steven Sparenborg, Sharon L Walsh
BACKGROUND: Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability...
December 14, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28088005/nicotine-hydrogen-tartrate-loaded-chitosan-nanoparticles-formulation-characterization-and-in-vitro-delivery-from-dry-powder-inhaler-formulation
#3
Hui Wang, Graeme George, Selena Bartlett, Changyou Gao, Nazrul Islam
This study reports the development of nanoparticles in the form of inhalable micro-aggregates of biodegradable chitosan (CS) loaded with nicotine hydrogen tartrate (NHT) for potential pulmonary delivery of nicotine from dry powder inhaler (DPI) formulations with prolonged release profile. The NHT-loaded CS particles were prepared using a water-in-oil emulsion crosslinking method. The prepared particles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for morphological studies; Zetasizer and Mastersizer were applied for particle size analysis...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087986/barriers-to-access-to-opioid-medicines-for-patients-with-opioid-dependence-a-review-of-legislation-and-regulations-in-eleven-central-and-eastern-european-countries
#4
Marjolein J M Vranken, Aukje K Mantel-Teeuwisse, Saskia Jünger, Lukas Radbruch, Willem Scholten, John A Lisman, Marija Subataite, Marie-Hélène D B Schutjens
BACKGROUND AND AIMS: Barriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 Central and Eastern European countries. METHODS: This study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project...
January 14, 2017: Addiction
https://www.readbyqxmd.com/read/28087970/liquid-chromatography-mass-spectrometry-high-resolution-for-the-determination-of-baclofen-and-its-metabolites-in-plasma-application-to-therapeutic-drug-monitoring
#5
Laurence Labat, Antonio Goncalves, Ana Rita Marques, Bénédicte Duretz, Bernard Granger, Xavier Declèves
Baclofen is actually used to manage alcohol dependence. This study describes a simple method using liquid chromatography coupled to high resolution mass spectrometry (LC-HR-MS) developed in plasma samples. This method was optimized to allow quantification of baclofen and determination of metabolic ratio of its metabolites, an oxidative deaminated metabolite of baclofen (M1) and its glucuronide form (M2). The LC-HR-MS method on Exactive® apparatus is a new developed method with all the advantages of the high resolution in full scan mode for the quantification of baclofen and detection of its metabolites in plasma...
January 14, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28087766/control-of-amygdala-circuits-by-5-ht-neurons-via-5-ht-and-glutamate-co-transmission
#6
Ayesha Sengupta, Marco Bocchio, David M Bannerman, Trevor Sharp, Marco Capogna
: The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Thus, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin (ChR2) genetically targeted to 5-HT neurons...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087697/development-of-high-affinity-and-high-specificity-inhibitors-of-metalloproteinase-14-through-computational-design-and-directed-evolution
#7
Valeria Arkadash, Gal Yosef, Jason Shirian, Itay Cohen, Yuval Horev, Moran Grossman, Irit Sagi, Evette S Radisky, Julia M Shifman, Niv Papo
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as three decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#8
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087384/epidermal-growth-factor-egf-fragment-guided-anticancer-theranostic-particles-for-ph-responsive-release-of-doxorubicin
#9
Myun Koo Kang, Wei Mao, Jun Bae Lee, Hyuk Sang Yoo
An EGF fragment and doxorubicin were chemically co-decorated on single magnetic nanoparticles for concomitant cancer targeting and treatment. Magnetic nanoparticles (MNPs) were prepared by the precipitation of ferric chloride hydrates in an ammonia solution and subsequent surface-functionalization with amines. The terminal thiol group of the EGF fragment (EGFfr) was first conjugated to surface amines of the MNPs using a heterofunctional crosslinker, and doxorubicin was sequentially conjugated to the MNPs via a hydrazone linker, where the degree of substation of the surface amines to EGF was varied from 1% to 40%...
January 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28087315/assessing-light-independent-effects-of-hypericin-on-cell-viability-ultrastructure-and-metabolism-in-human-glioma-and-endothelial-cells
#10
Veronika Huntosova, Marta Novotova, Zuzana Nichtova, Lucia Balogova, Maria Maslanakova, Dana Petrovajova, Katarina Stroffekova
Cell exposure to light-independent effects of photosensitizers (PS) used in PDT is clinically relevant when PS affect the pro-apoptotic cascade.In many malignant cells, Hypericin (Hyp) has PS displayed light-dependent anti-proliferative and cytotoxic effects with no cytotoxicity in the dark. Recent studies have shown that Hyp also exhibited light-independent cytotoxic effects in a wide range of concentrations. The molecular mechanisms underlying Hyp light-independent (dark) toxicity may be due to its interaction with different molecules at the Hyp accumulation sites including mitochondria, and these mechanisms are not understood in detail...
January 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28087264/independent-impedimetric-analysis-of-two-cell-populations-co-cultured-on-opposite-sides-of-a-porous-support
#11
Kathrin Hajek, Joachim Wegener
The transepithelial or -endothelial electrical resistance (TEER) is a very common and routinely recorded parameter describing the expression of barrier-forming cell-cell contacts (tight junctions) in quantitative terms. To determine TEER, barrier-forming cell monolayers are cultured on porous filter supports that separate two fluid compartments. The frequency-dependent impedance of the cell layer is then recorded and analyzed by means of equivalent circuit modeling providing TEER and the cell layer capacitance...
January 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28087254/anti-diabetic-drug-metformin-dilates-retinal-blood-vessels-through-activation-of-amp-activated-protein-kinase-in-rats
#12
Asami Mori, Eriko Ishikawa, Tomoyo Amano, Kenji Sakamoto, Tsutomu Nakahara
The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087221/varenicline-provokes-impulsive-action-by-stimulating-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-in-the-infralimbic-cortex-in-a-nicotine-exposure-status-dependent-manner
#13
Yu Ohmura, Hitomi Sasamori, Iku Tsutsui-Kimura, Takeshi Izumi, Takayuki Yoshida, Mitsuhiro Yoshioka
Higher impulsivity is a risk factor for criminal involvement and drug addiction. Because nicotine administration enhances impulsivity, the effects of stop-smoking aids stimulating nicotinic acetylcholine receptors (nAChRs) on impulsivity must be determined in different conditions. Our goals were 1) to confirm the relationship between varenicline, a stop-smoking aid and α4β2 nAChR partial agonist, and impulsivity, 2) to elucidate the mechanisms underlying the effects of varenicline, 3) to examine whether a low dose of varenicline that does not evoke impulsive action could block the stimulating effects of nicotine on impulsive action, 4) to determine whether the route of administration could modulate the effects of varenicline on impulsive action, and 5) to determine whether the effects of varenicline on impulsivity could be altered by smoking status...
January 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28086980/inflammation-in-epileptogenesis-after-traumatic-brain-injury
#14
REVIEW
Kyria M Webster, Mujun Sun, Peter Crack, Terence J O'Brien, Sandy R Shultz, Bridgette D Semple
BACKGROUND: Epilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and psychosocial outcomes for TBI survivors, and epilepsy after TBI is often resistant to existing anti-epileptic drugs. The development of post-traumatic epilepsy (PTE) occurs in a complex neurobiological environment characterized by ongoing TBI-induced secondary injury processes. Neuroinflammation is an important secondary injury process, though how it contributes to epileptogenesis, and the development of chronic, spontaneous seizure activity, remains poorly understood...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28086956/differential-expression-of-e-type-prostanoid-receptors-2-and-4-in-microglia-stimulated-with-lipopolysaccharide
#15
Ester Bonfill-Teixidor, Amaia Otxoa-de-Amezaga, Miriam Font-Nieves, M Glòria Sans-Fons, Anna M Planas
BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28086831/evaluation-of-the-cytotoxicity-of-the-bithionol-cisplatin-combination-in-a-panel-of-human-ovarian-cancer-cell-lines
#16
Vijayalakshmi N Ayyagari, Tsung-Han Jeff Hsieh, Paula L Diaz-Sylvester, Laurent Brard
BACKGROUND: Combination drug therapy appears a promising approach to overcome drug resistance and reduce drug-related toxicities in ovarian cancer treatments. In this in vitro study, we evaluated the antitumor efficacy of cisplatin in combination with Bithionol (BT) against a panel of ovarian cancer cell lines with special focus on cisplatin-sensitive and cisplatin-resistant cell lines. The primary objectives of this study are to determine the nature of the interactions between BT and cisplatin and to understand the mechanism(s) of action of BT-cisplatin combination...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28086782/in-vivo-antiplasmodial-activity-and-toxicological-assessment-of-hydroethanolic-crude-extract-of-ajuga-remota
#17
Aschalew Nardos, Eyasu Makonnen
BACKGROUND: Malaria is one of the most life-threatening health problems worldwide and treatment has been compromised by drug resistance. Identifying lead molecules from natural products might help to find better anti-malarial drugs, since those obtained from natural sources are still effective against malarial parasites. This study aimed at investigating the in vivo antiplasmodial activity of crude extract of the leaves of Ajuga remota together with its safety in mice models. METHODS: In vivo parasite growth inhibitory effect of crude extract was assessed in mice inoculated with Plasmodium berghei (ANKA strain)...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28081594/management-of-direct-antiviral-agent-failures
#18
REVIEW
María Buti, Rafael Esteban
The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied...
December 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28081499/screening-active-compounds-from-corydalis-yanhusuo-by-combining-high-expression-vegf-receptor-hek293-cell-membrane-chromatography-with-hplc-esi-it-tof-msn-method
#19
Fen Wei, Qi Hu, Jing Huang, Shengli Han, Sicen Wang
Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay...
January 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28081462/in%C3%A2-vitro-evaluation-of-biodegradable-lignin-based-nanoparticles-for-drug-delivery-and-enhanced-antiproliferation-effect-in-cancer-cells
#20
Patrícia Figueiredo, Kalle Lintinen, Alexandros Kiriazis, Ville Hynninen, Zehua Liu, Tomás Bauleth-Ramos, Antti Rahikkala, Alexandra Correia, Tomáš Kohout, Bruno Sarmento, Jari Yli-Kauhaluoma, Jouni Hirvonen, Olli Ikkala, Mauri A Kostiainen, Hélder A Santos
Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation...
January 2, 2017: Biomaterials
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