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https://www.readbyqxmd.com/read/29356216/treatment-gap-for-anxiety-disorders-is-global-results-of-the-world-mental-health-surveys-in-21-countries
#1
Jordi Alonso, Zhaorui Liu, Sara Evans-Lacko, Ekaterina Sadikova, Nancy Sampson, Somnath Chatterji, Jibril Abdulmalik, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Laura H Andrade, Ronny Bruffaerts, Graça Cardoso, Alfredo Cia, Silvia Florescu, Giovanni de Girolamo, Oye Gureje, Josep M Haro, Yanling He, Peter de Jonge, Elie G Karam, Norito Kawakami, Viviane Kovess-Masfety, Sing Lee, Daphna Levinson, Maria Elena Medina-Mora, Fernando Navarro-Mateu, Beth-Ellen Pennell, Marina Piazza, José Posada-Villa, Margreet Ten Have, Zahari Zarkov, Ronald C Kessler, Graham Thornicroft
BACKGROUND: Anxiety disorders are a major cause of burden of disease. Treatment gaps have been described, but a worldwide evaluation is lacking. We estimated, among individuals with a 12-month DSM-IV (where DSM is Diagnostic Statistical Manual) anxiety disorder in 21 countries, the proportion who (i) perceived a need for treatment; (ii) received any treatment; and (iii) received possibly adequate treatment. METHODS: Data from 23 community surveys in 21 countries of the World Mental Health (WMH) surveys...
January 22, 2018: Depression and Anxiety
https://www.readbyqxmd.com/read/29355662/biotherapeutics-in-non-clinical-development-strengthening-the-interface-between-safety-pharmacokinetics-pharmacodynamics-and-manufacturing
#2
Peter Ulrich, Guenter Blaich, Andreas Baumann, Rajni Fagg, Adam Hey, Andrea Kiessling, Sven Kronenberg, Rikke Hvid Lindecrona, Silke Mohl, Wolfgang F Richter, Jay Tibbitts, Flavio Crameri, Lucinda Weir
Biological drugs comprise a wide field of different modalities with respect to structure, pharmacokinetics and pharmacological function. Considerable non-clinical experience in the development of proteins (e.g. insulin) and antibodies has been accumulated over the past thirty years. In order to improve the efficacy and the safety of these biotherapeutics, Fc modifications (e.g. Fc silent antibody versions), combinations (antibody-drug conjugates, protein-nanoparticle combinations), and new constructs (darpins, fynomers) have been introduced...
January 16, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29355527/isovitexin-iv-induces-apoptosis-and-autophagy-in-liver-cancer-cells-through-endoplasmic-reticulum-stress
#3
Sheng-Xiang Lv, Xiao Qiao
Liver cancer is a leading cause of cancer death worldwide, and novel chemotherapeutic drugs to suppress liver cancer are urgently required. Isovitexin (IV), a glycosylflavonoid, is extracted from rice hulls of Oryza sativa, and has various biological activities. However, the anti-tumor effect of IV against liver cancer has not yet been demonstrated in vitro or in vivo. In the present study, we showed that IV significantly suppressed the growth of liver cancer cells. Mechanistic studies indicated that IV induced apoptosis by the mitochondrial apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria...
January 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29353047/clinical-profile-of-nonresponders-to-surgical-myectomy-with-obstructive-hypertrophic-cardiomyopathy
#4
Sophie Wells, Ethan J Rowin, Griffin Boll, Hassan Rastegar, Wendy Wang, Martin S Maron, Barry J Maron
BACKGROUND: In the vast majority of patients with obstructive hypertrophic cardiomyopathy and drug-refractory heart failure, surgical myectomy results in reversal of heart failure symptoms. However, a small patient subgroup fails to experience sustained postoperative improvement despite relief of left ventricular outflow obstruction. Clinical profile of such patients has not been well defined. METHODS: Consecutive obstructive hypertrophic cardiomyopathy patients undergoing myectomy at Tufts Medical Center for drug refractory NYHA III/IV heart failure symptoms, 2004 to 2017, were followed postoperatively for 2...
January 15, 2018: American Journal of Medicine
https://www.readbyqxmd.com/read/29352745/negative-supercoiling-of-dna-by-gyrase-is-inhibited-in-salmonella-enterica-serovar-typhimurium-during-adaptation-to-acid-stress
#5
Aoife M Colgan, Heather J Quinn, Stefani C Kary, Lesley A Mitchenall, Anthony Maxwell, Andrew Ds Cameron, Charles J Dorman
DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4 to 5) macrophage vacuole and DNA relaxation correlates with upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane-located inhibitor of proton-driven F1 F0 ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation...
January 20, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29352476/pharmacokinetic-profiles-of-the-active-metamizole-metabolites-after-four-different-routes-of-administration-in-healthy-dogs
#6
M Giorgi, B Łebkowska-Wieruszewska, A Lisowski, H Owen, A Poapolathep, T W Kim, V De Vito
Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment, four-phase, unpaired, crossover study design...
January 19, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29352472/the-bioequivalence-of-a-single-intravenous-administration-of-the-anesthetic-alfaxalone-in-cyclodextrin-versus-alfaxalone-in-cyclodextrin-plus-preservatives-in-cats
#7
K Pasloske, M G Ranasinghe, S Sauer, J Hare
To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single-dose, randomized, two-period, two-sequence, cross-over bioequivalence study with a 7-day washout period between treatments. Twenty-four (12 neutered males and 12 intact females), healthy, adult cats weighing 4...
January 19, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29350254/sacubitril-valsartan-for-heart-failure-with-reduced-left-ventricular-ejection-fraction-a%C3%A2-retrospective-cohort-study
#8
R De Vecchis, C Ariano, G Di Biase, M Noutsias
BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs...
January 19, 2018: Herz
https://www.readbyqxmd.com/read/29349448/a-study-on-platinum-iv-species-containing-an-estrogen-receptor-modulator-to-reverse-tamoxifen-resistance-of-breast-cancer
#9
Weiwei Hu, Jian Zhao, Wuyang Hua, Shaohua Gou
Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and platinum(ii) drugs were designed and synthesized for targeting estrogen receptors (ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity against breast cancer cells, but also reversed the tamoxifen resistance of TamR-MCF-7 cancer cells. Computational docking assays together with cellular uptake data demonstrated that the ER ligand portion of these conjugates plays a targeting role in ER-positive tumor cells and promotes the uptake of platinum via an estrogen receptor-mediated pathway...
January 19, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29346804/trabodenoson-an-adenosine-mimetic-with-a1-receptor-selectivity-lowers-intraocular-pressure-by-increasing-conventional-outflow-facility-in-mice
#10
Guorong Li, Karen Y Torrejon, Andrea M Unser, Feryan Ahmed, Iris D Navarro, Rudolf A Baumgartner, David S Albers, W Daniel Stamer
Purpose: To evaluate the relationship between the IOP-lowering effect of trabodenoson and the associated structural and functional changes in the trabecular meshwork (TM). Methods: Six independent cohorts of young and aged mice were exposed to three different topical once-a-day formulations of trabodenoson and eyes were compared to those treated with placebo drops. IOP was measured daily just before drug administration using rebound tonometry. Outflow facility was measured in enucleated eyes...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29345599/crystalline-ethylene-oxide-and-propylene-oxide-triblock-copolymer-solid-dispersion-enhance-solubility-stability-and-promoting-time-controllable-release-of-curcumin
#11
Thais Francine Ribeiro Alves, Franciely Lopes, Marcia Rebelo, Juliana Souza, Katiusca Pontes, Carolina Santos, Patricia Severino, Jose Junior, Daniel Komatsu, Marco Vinicius Chaud
AIMS AND BACKGROUND: The design and development of an effective medicine are however often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR...
January 17, 2018: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29344328/management-of-functional-dyspepsia-state-of-the-art-and-emerging-therapies
#12
REVIEW
Hiroshi Yamawaki, Seiji Futagami, Mako Wakabayashi, Noriko Sakasegawa, Shuhei Agawa, Kazutoshi Higuchi, Yasuhiro Kodaka, Katsuhiko Iwakiri
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29342497/non-antipsychotic-catecholaminergic-drugs-for-antipsychotic-induced-tardive-dyskinesia
#13
REVIEW
Hany G El-Sayeh, John Rathbone, Karla Soares-Weiser, Hanna Bergman
BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: 1...
January 18, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29339383/new-shuttle-vectors-for-gene-cloning-and-expression-in-multidrug-resistant-acinetobacter-species
#14
Massimiliano Lucidi, Federica Runci, Giordano Rampioni, Emanuela Frangipani, Livia Leoni, Paolo Visca
Understanding bacterial pathogenesis requires adequate genetic tools to assess the role of individual virulence determinants by mutagenesis and complementation assays, as well as for homologous and heterologous expression of cloned genes. Our knowledge of Acinetobacter baumannii pathogenesis has so far been limited by the scarcity of genetic tools to manipulate multi drug resistant (MDR) epidemic strains which are responsible for most of infections. Here, we report the construction of new multi-purpose shuttle plasmids, namely pVRL1 and pVRL2, which can efficiently replicate in Acinetobacter sp...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29338895/feasibility-of-total-intravenous-anesthesia-by-cardiologists-with-the-support-of-anesthesiologists-during-catheter-ablation-of-atrial-fibrillation
#15
Takanori Yamaguchi, Yusuke Shimakawa, Shinji Mitsumizo, Akira Fukui, Yuki Kawano, Toyokazu Otsubo, Yuya Takahashi, Kei Hirota, Takeshi Tsuchiya, Kenichi Eshima
BACKGROUND: The optimal methodology for sedation and anesthesia during atrial fibrillation (AF) ablation has not been well established. We assessed the feasibility of total intravenous anesthesia (TIVA) by cardiologists with support from anesthesiologists during AF ablation and quality of pulmonary vein isolation (PVI) and single procedure success rate at 12 months. METHODS: TIVA was performed by cardiologists using IV propofol and fentanyl under controlled ventilation via i-gel™ without neuromuscular blocking drugs in 160 consecutive patients (80 nonparoxysmal) with no anticipated difficult airway or other severe diseases...
January 12, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#16
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29337438/3d-e-chem-structural-cheminformatics-workflows-for-computer-aided-drug-discovery
#17
Albert J Kooistra, Marton Vass, Ross McGuire, Rob Leurs, Iwan Jp de Esch, Gerrit Vriend, Stefan Verhoeven, Chris de Graaf
eScience technologies are needed to process the information available in many heterogeneous types of protein-ligand interaction data and to capture these data into models that enable the design of efficacious and safe medicines. Here we present scientific KNIME tools and workflows that enable the integration of chemical, pharmacological, and structural information for: i) structure-based bioactivity data mapping, ii) structure-based identification of scaffold replacement strategies for ligand design, iii) ligand-based target prediction, iv) protein sequence-based binding site identification and ligand repurposing, and v) structure-based pharmacophore comparison for ligand repurposing across protein families...
January 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29336140/synthesis-of-cisplatin-iv-prodrug-tethered-cufes2-nanoparticles-in-tumor-targeted-chemotherapy-and-photothermal-therapy
#18
Wubshet Mekonnen Girma, Shin-Hwa Tzing, Po-Jen Tseng, Chih-Ching Huang, Yong-Chien Ling, Jia-Yaw Chang
In this study, for the first time, CuFeS2 nanocrystals were successfully prepared through a facile noninjection-based synthetic strategy, by reacting Cu and Fe precursors with dodecanethiol in a 1-octadecene solvent. This one-pot noninjection strategy features easy handling, large-scale production, and high synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2 nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and showed improved biocompatibility, but also possessed a tumor-specific targeting ability of cancer cells bearing the cluster determinant 44 (CD44) receptors...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29329993/pulmonary-arterial-hypertension-in-four-patients-treated-by-leflunomide
#19
Valentin Coirier, Alain Lescoat, Céline Chabanne, Maxime Fournet, Guillaume Coiffier, Stéphane Jouneau, Elisabeth Polard, Patrick Jégo
Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug-induced, mostly following treatment by appetite-suppressant drugs. We report four cases of patients who developed PAH following a treatment by leflunomide for rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue disease. All patients described a progressive dyspnea from grade II to IV of NYHA classification; clinical examination found signs of heart failure. PAH was finally diagnosed and confirmed by right heart catheterisation...
January 9, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29329232/novel-6-and-7-substituted-coumarins-with-inhibitory-action-against-lipoxygenase-and-tumor-associated-carbonic-anhydrase-ix
#20
Aikaterini Peperidou, Silvia Bua, Murat Bozdag, Dimitra Hadjipavlou-Litina, Claudiu T Supuran
A series of carboxamide derivatives of 6- and 7-substituted coumarins have been prepared by an original procedure starting from the corresponding 6- or 7-hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained ester was converted to the corresponding carboxylic acids which were thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX)...
January 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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