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https://www.readbyqxmd.com/read/28641293/measuring-concurrent-polydrug-use-in-general-populations-a-critical-assessment
#1
Karoliina Karjalainen, Kristiina Kuussaari, Kati Kataja, Christoffer Tigerstedt, Pekka Hakkarainen
BACKGROUND/AIMS: Polydrug use is a complicated phenomenon that is measured in a wide variety of different ways. Using Finland as an example, we aimed to demonstrate how the prevalence and prevalence trends of concurrent polydrug use (CPU) varied in the general population based on the different measurements used. METHODS: Population-based Drug Surveys conducted every 4 years during 1998-2014 were used. CPU was measured with different measurements: strict, medial and loose definition of CPU, which were based on different combinations of alcohol, illicit drugs, pharmaceutical drugs and cigarettes used during the last 12 months/30 days...
June 23, 2017: European Addiction Research
https://www.readbyqxmd.com/read/28641128/expectancy-of-impairment-attenuates-marijuana-induced-risk-taking
#2
Rachel L Gunn, Linda Skalski, Jane Metrik
BACKGROUND: Marijuana use has been associated with increased risk-taking and impulsive behavior. While pharmacologic effects of marijuana can lead to inhibitory impairment, expectancy of potential impairment may result in compensatory behavioral response by decreasing impulsive decisions and risky behaviors. With the increases in marijuana use and related problems, a better understanding of the individual characteristics associated with marijuana intoxication and risky behavior is needed...
June 13, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28641055/long-term-safety-evaluation-of-natalizumab-for-the-treatment-of-multiple-sclerosis
#3
Marinella Clerico, Carlo Alberto Artusi, Alessandra Di Liberto, Simona Rolla, Valentina Bardina, Pierangelo Barbero, Stefania Federica De Mercanti, Luca Durelli
Introduction Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out because of the risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV). Areas covered This review analyzes all the safety aspects related to the use of natalizumab in MS patients. Fatigue and allergic reactions are not-severe adverse events (AEs) occurring more frequently than placebo and no differences in serious AEs (SAE) have been observed comparing to interferon-β1a during clinical trials...
June 22, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28640990/opiate-antagonists-do-not-interfere-with-the-clinical-benefits-of-stimulants-in-adhd-a-double-blind-placebo-controlled-trial-of-the-mixed-opioid-receptor-antagonist-naltrexone
#4
Thomas J Spencer, Pradeep Bhide, Jinmin Zhu, Stephen V Faraone, Maura Fitzgerald, Amy M Yule, Mai Uchida, Andrea E Spencer, Anna M Hall, Ariana J Koster, Joseph Biederman
OBJECTIVE: Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015...
June 20, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28640849/motility-in-blastogregarines-apicomplexa-native-and-drug-induced-organisation-of-siedleckia-nematoides-cytoskeletal-elements
#5
Andrea Valigurová, Naděžda Vaškovicová, Andrei Diakin, Gita G Paskerova, Timur G Simdyanov, Magdaléna Kováčiková
Recent studies on motility of Apicomplexa concur with the so-called glideosome concept applied for apicomplexan zoites, describing a unique mechanism of substrate-dependent gliding motility facilitated by a conserved form of actomyosin motor and subpellicular microtubules. In contrast, the gregarines and blastogregarines exhibit different modes and mechanisms of motility, correlating with diverse modifications of their cortex. This study focuses on the motility and cytoskeleton of the blastogregarine Siedleckia nematoides Caullery et Mesnil, 1898 parasitising the polychaete Scoloplos cf...
2017: PloS One
https://www.readbyqxmd.com/read/28640722/stroke-ineffective-tube-securement-reduces-nutrition-and-drug-treatment
#6
Sophie Brazier, Stephen J Taylor, Kaylee Allan, Rowan Clemente, Deirdre Toher
Stroke patients with dysphagia often depend on nutrition, hydration and medication via nasogastric (NG) feeding tubes. Securing tubes using tape is associated with repeated tube loss. In this study, the authors determined cause and effect by auditing tube placement methods, delays incurred, duration and costs. Of 202 NG tube placements in 75 patients, 67 placements occurred in 17 patients over a full course of enteral nutrition (EN) and 40 of these placements were tracked. Tubes were secured by tape in 100%, mittens 31% and special observation 5...
June 22, 2017: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/28640596/drug-target-kinetics-in-drug-discovery
#7
Peter J Tonge
The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28637198/multi-target-activity-of-hemidesmus-indicus-decoction-against-innovative-hiv-1-drug-targets-and-characterization-of-lupeol-mode-of-action
#8
Francesca Esposito, Manuela Mandrone, Claudia Del Vecchio, Ilaria Carli, Simona Distinto, Angela Corona, Mariacaterina Lianza, Dario Piano, Massimo Tacchini, Elias Maccioni, Filippo Cottiglia, Elisa Saccon, Ferruccio Poli, Cristina Parolin, Enzo Tramontano
Despite the availability of several anti-retrovirals there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors...
June 20, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#9
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#10
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#11
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28636875/effects-of-prenatal-binge-like-ethanol-exposure-and-maternal-stress-on-postnatal-morphological-development-of-hippocampal-neurons-in-rats
#12
Ewa Jakubowska-Dogru, Birsen Elibol, Ilknur Dursun, Sinan Yürüker
BACKGROUND: Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months...
June 18, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28636707/incidence-and-predictors-of-opioid-prescription-at-discharge-after-traumatic-injury
#13
Muhammad Ali Chaudhary, Andrew J Schoenfeld, Alyssa F Harlow, Anju Ranjit, Rebecca Scully, Ritam Chowdhury, Meesha Sharma, Stephanie Nitzschke, Tracey Koehlmoos, Adil H Haider
Importance: In the current health care environment with increased scrutiny and growing concern regarding opioid use and abuse, there has been a push toward greater regulation over prescriptions of opioids. Trauma patients represent a population that may be affected by this regulation, as the incidence of pain at hospital discharge is greater than 95%, and opioids are considered the first line of treatment for pain management. However, the use of opioid prescriptions in trauma patients at hospital discharge has not been explored...
June 21, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28636670/identification-of-novel-small-molecules-that-inhibit-stat3-dependent-transcription-and-function
#14
Iryna Kolosenko, Yasmin Yu, Sander Busker, Matheus Dyczynski, Jianping Liu, Martin Haraldsson, Caroline Palm Apergi, Thomas Helleday, Katja Pokrovskaja Tamm, Brent D G Page, Dan Grander
Activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been linked to several processes that are critical for oncogenic transformation, cancer progression, cancer cell proliferation, survival, drug resistance and metastasis. Inhibition of STAT3 signaling has shown a striking ability to inhibit cancer cell growth and therefore, STAT3 has become a promising target for anti-cancer drug development. The aim of this study was to identify novel inhibitors of STAT-dependent gene transcription...
2017: PloS One
https://www.readbyqxmd.com/read/28636622/inhibition-of-hepatitis-b-viral-entry-by-nucleic-acid-polymers-in-heparg-cells-and-primary-human-hepatocytes
#15
Clément Guillot, Nora Martel, Françoise Berby, Isabelle Bordes, Olivier Hantz, Matthieu Blanchet, Camille Sureau, Andrew Vaillant, Isabelle Chemin
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure...
2017: PloS One
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#16
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636290/sulforaphane-protection-against-the-development-of-doxorubicin-induced-chronic-heart-failure-is-associated-with-nrf2-upregulation
#17
Yang Bai, Qiang Chen, Yun-Peng Sun, Xuan Wang, Li Lv, Li-Ping Zhang, Jin-Sha Liu, Song Zhao, Xiao-Lu Wang
Doxorubicin (DOX) is an anthracycline anti-tumor drug. However, its clinical use is limited by dose-dependent cardiotoxicity, and even progresses to chronic heart failure (CHF). OBJECTIVE: This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX-induced CHF. METHODS: Male Sprague Dawley rats who received treatment for six weeks were divided into four groups (n=30 per group): control, SFN, DOX, and DOX plus SFN group. RESULTS: Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#18
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28636017/effect-of-cisplatin-on-the-transport-activity-of-pii-type-atpases
#19
Francesco Tadini-Buoninsegni, Giacomo Sordi, Serena Smeazzetto, Giovanni Natile, Fabio Arnesano
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu(+)-ATPases (ATP7A and ATP7B) and Na(+),K(+)-ATPase. Cisplatin-induced inhibition of Na(+),K(+)-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+),K(+)-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28635961/hypoxia-induced-mobilization-of-nhe6-to-the-plasma-membrane-triggers-endosome-hyperacidification-and-chemoresistance
#20
Fabrice Lucien, Pierre-Paul Pelletier, Roxane R Lavoie, Jean-Michel Lacroix, Sébastien Roy, Jean-Luc Parent, Dominique Arsenault, Kelly Harper, Claire M Dubois
The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification...
June 21, 2017: Nature Communications
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