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Ademar Francisco de Oliveira, Gêssyca Adryene de Menezes Silva, Débora Milenna Xavier Almeida
Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results...
July 2016: Einstein
Carlos Walter Sobrado, Lucas Faraco Sobrado
Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches...
July 2016: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Dirk Fahrenkamp, Jinyu Li, Sabrina Ernst, Hildegard Schmitz-Van de Leur, Nicolas Chatain, Andrea Küster, Steffen Koschmieder, Bernhard Lüscher, Giulia Rossetti, Gerhard Müller-Newen
STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins...
October 18, 2016: Scientific Reports
Susanne Hafner, Sabine Haubensak, Tanusree Paul, Oliver Zolk
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines...
October 2016: Deutsche Medizinische Wochenschrift
Fatiha Benmansour, Iuni Trist, Bruno Coutard, Etienne Decroly, Gilles Querat, Andrea Brancale, Karine Barral
With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase...
October 5, 2016: European Journal of Medicinal Chemistry
Bart V J Cuppen, Johannes W G Jacobs, Evert-Jan Ter Borg, Anne C A Marijnissen, Johannes W J Bijlsma, Floris P J G Lafeber, Jacob M van Laar
OBJECTIVES: Despite the success of TNF-alpha inhibitor (TNFi) treatment in rheumatoid arthritis (RA), a substantial number of patients necessitate discontinuation. Prediction thereof would be clinically relevant and guide the decision whether to start TNFi treatment. METHODS: Data were used from the observational BiOCURA cohort, in which patients initiating biological treatment were enrolled and followed up for one year. In the model development cohort (n=192), a model predicting TNFi discontinuation was built using Cox-regression with backward selection (p<0...
October 7, 2016: Clinical and Experimental Rheumatology
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
Huawei Zhang, Phillip Crews, Karen Tenney, Frederick A Valeriote
BACKGROUND: A growing evidence indicates that marine sponge Phyllospongia sp. is one of rich sources of 20, 24-bishomoscalane sesterterpenes with potent biological activities. In order to search more bioactive 20, 24-bishomoscalane sesterterpenes for new drug discovery, chemical investigation was carried out on an Indonesian marine sponge P. papyrecea. METHODS: Bioassay-guided fractionation was carried out on its dichloromethane extract. And nine compounds were purified and isolated using HPLC...
October 7, 2016: Medicinal Chemistry
Liqin Wang, Miao Xu, Noel Southall, Wei Zheng, Shuishu Wang
Tuberculosis (TB) still kills over 1.5 million people per year despite available anti-TB drugs. The emergence of drug-resistant TB poses a major threat to public health and prompts for an urgent need for new and more effective drugs. The long duration needed to treat TB by the current TB drugs, which target the essential cellular activities, inevitably leads to the emergence of drug-resistance. PhoP of Mycobacterium tuberculosis (MTB), an essential virulence factor, is a novel target for drug development. Guided by the crystal structure of the PhoP-DNA complex, we designed and developed a robust high-throughput screening assay for identification of PhoP inhibitors that disrupt the PhoP-DNA binding...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Zhongmin Wang, Yuhao Liu, Yu Xu, Chuanyu Gao, Yan Chen, Hongxing Luo
BACKGROUND: WE AIMED TO PROSPECTIVELY EVALUATE THE: use of 3-dimensional printing (3DP) for the percutaneous transcatheter closure of a secundum atrial septal defect (ASD) with rim deficiency less than 5 mm. METHODS: Patients with ASD were scanned using multi-slice computed tomography to acquire raw data for virtual 3DP reconstruction models. Different ASD occluders were tried on the 3DP models to select the optimal size for intraoperative use. The patients were followed up 1 month postoperatively, and 3DP models were again manufactured to observe the operative effects...
October 17, 2016: Cardiology Journal
Xiu Chen, Peng Lu, Dan-Dan Wang, Su-Jin Yang, Ying Wu, Hong-Yu Shen, Shan-Liang Zhong, Jian-Hua Zhao, Jin-Hai Tang
PURPOSE: Chemoresistance mediated by miRNAs in breast cancer have been already validated by previous studies in vitro, while little is known concerning the expression of them in vivo. The aim of this study was to investigate the role of miR-222, miR-29a, miR-34a, miR-130a, miR-90b, miR-200b, miR-452, miR-197, miR-138, miR-210, miR-423, miR-4298, miR-4644, miR-139, miR-1246, miR-1268a, miR-140, miR-149, miR-3178, miR-3613, miR-4258, miR-574, miR-671, miR-6780b, miR-7107, miR-744 and miR-7847 linked to drug resistance in breast cancer formalin-fixed paraffin-embedded tissues and the association of prognosis with miRNAs, thus providing effective targets in chemotherapy, as well as potential biomarkers for guiding effective treatments of breast cancer...
October 13, 2016: Gene
Imke H Bartelink, Arief Lalmohamed, Elisabeth M L van Reij, Christopher C Dvorak, Rada M Savic, Juliette Zwaveling, Robbert G M Bredius, Antoine C G Egberts, Marc Bierings, Morris Kletzel, Peter J Shaw, Christa E Nath, George Hempel, Marc Ansari, Maja Krajinovic, Yves Théorêt, Michel Duval, Ron J Keizer, Henrique Bittencourt, Moustapha Hassan, Tayfun Güngör, Robert F Wynn, Paul Veys, Geoff D E Cuvelier, Sarah Marktel, Robert Chiesa, Morton J Cowan, Mary A Slatter, Melisa K Stricherz, Cathryn Jennissen, Janel R Long-Boyle, Jaap Jan Boelens
BACKGROUND: Intravenous busulfan combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic haemopoietic cell transplantation (HCT). The best method to estimate busulfan exposure and optimum exposure in children or young adults remains unclear. We therefore assessed three approaches to estimate intravenous busulfan exposure (expressed as cumulative area under the curve [AUC]) and associated busulfan AUC with clinical outcomes in children or young adults undergoing allogeneic HCT...
October 13, 2016: Lancet Haematology
Lional Rajappa-Titu, Takuma Suematsu, Paola Munoz-Tello, Marius Long, Özlem Demir, Kevin J Cheng, Jason R Stagno, Hartmut Luecke, Rommie E Amaro, Inna Aphasizheva, Ruslan Aphasizhev, Stéphane Thore
Terminal uridyltransferases (TUTases) execute 3' RNA uridylation across protists, fungi, metazoan and plant species. Uridylation plays a particularly prominent role in RNA processing pathways of kinetoplastid protists typified by the causative agent of African sleeping sickness, Trypanosoma brucei In mitochondria of this pathogen, most mRNAs are internally modified by U-insertion/deletion editing while guide RNAs and rRNAs are U-tailed. The founding member of TUTase family, RNA editing TUTase 1 (RET1), functions as a subunit of the 3' processome in uridylation of gRNA precursors and mature guide RNAs...
October 15, 2016: Nucleic Acids Research
Shota Hamada, Martin C Gulliford
OBJECTIVE: to evaluate primary care drug utilisation during the last year of life, focusing on antidiabetic and cardiovascular drugs, in patients of advanced age with diabetes. DESIGN: population-based cohort study. SETTING: primary care database in the UK. SUBJECTS: patients with type 2 diabetes who died at over 80 years of age between 2011 and 13. METHODS: main outcome measures included proportions of patients prescribed different classes of drugs, comparing the first (Q1) and the fourth quarters (Q4) of the last year of life...
October 15, 2016: Age and Ageing
O Szerkus, J Jacyna, A Gibas, M Sieczkowski, D Siluk, M Matuszewski, R Kaliszan, M J Markuszewski
Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI-MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10mg) was carried out using homogenization and filtration steps. Analyses were performed within 3...
October 8, 2016: Journal of Pharmaceutical and Biomedical Analysis
Dong-Ho Shin, Sung-Jin Hong, Gary S Mintz, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Myeong-Ki Hong
OBJECTIVES: The aim of this study was to evaluate the clinical usefulness of intravascular ultrasound (IVUS)-guided new-generation drug-eluting stent (DES) implantation using a meta-analysis of individual patient-level data from randomized trials. BACKGROUND: Published randomized trials that compare IVUS-guided versus angiography-guided new-generation DES implantation are scarce. METHODS: Searches of the MEDLINE, Embase, and Cochrane databases were performed to find randomized trials that compared IVUS-guided versus angiography-guided new-generation DES implantation...
October 6, 2016: JACC. Cardiovascular Interventions
Xiang Cheng, Shu-Guang Zhao, Xuan Xiao, Kuo-Chen Chou
MOTIVATION: Given a compound, can we predict which ATC (Anatomical Therapeutic Chemical) class/classes it belongs to? It is a challenging problem since the information thus obtained can be used to deduce its possible active ingredients, as well as its therapeutic, pharmacological and chemical properties. And hence the pace of drug development could be substantially expedited. But this problem is by no means an easy one. Particularly, some drugs or compounds may belong to two or more ATC classes...
October 14, 2016: Bioinformatics
Vitor Mendes, Tom L Blundell
Fragment-based drug discovery is now widely used in academia and industry to obtain small molecule inhibitors for a given target and is established for many fields of research including antimicrobials and oncology. Many molecules derived from fragment-based approaches are already in clinical trials and two-vemurafenib and venetoclax-are on the market, but the approach has been used sparsely in the tuberculosis field. Here, we describe the progress of our group and others, and examine the most recent successes and challenges in developing compounds with antimycobacterial activity...
October 11, 2016: Drug Discovery Today
David van Duin, Paula D Strassle, Lauren M DiBiase, Anne M Lachiewicz, William A Rutala, Timothy Eitas, Robert Maile, Hajime Kanamori, David J Weber, Bruce A Cairns, Sonia Napravnik, Samuel W Jones
BACKGROUND: Infections are an important cause of morbidity and mortality after burn injuries. Here, we describe the time line of infections and pathogens after burns. METHODS: A retrospective study was performed in a large tertiary care burn center from 2004-2013. Analyses were performed on health care-associated infections (HAIs) meeting Centers for Disease Control and Prevention criteria and on all positive cultures. Incidence rates per 1,000 days were calculated for specific HAI categories and pathogens and across hospitalization time (week 1, weeks 2-3, and week ≥4)...
October 11, 2016: American Journal of Infection Control
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