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New drug therapy

Wan-Ju Lee, Leslie Briars, Todd A Lee, Gregory S Calip, Katie J Suda, Glen T Schumock
OBJECTIVE: To characterize the use of tumor necrosis factor-alpha inhibitors (TNFI) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). METHODS: Patients with incident JIA or RA were identified using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months...
October 25, 2016: Pharmacotherapy
L Hepburn, D J Hijnen, B R Sellman, T Mustelin, M A Sleeman, R D May, I Strickland
Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of UK children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonised with Staphylococcus aureus (S. aureus) and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitisation, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection...
October 25, 2016: British Journal of Dermatology
Jan Liliemark, Lars Lööf, Gustaf Befrits, Stefan Back, Lars Sandman
The County Council's board for new therapies (the NT Council) provides recommendations on the use of new drugs based on the ethical platform of priorities, founded by the Swedish parliament. The Council has formulated a policy that interprets the parliamentary ethical platform and operationalize its need and solidarity principle and cost effectiveness principle in four dimensions. The NT Council weighs the health economic evaluation of the drug and the four dimensions: the severity of the condition, the rarity of the condition, the effect size and the data reliability to determine the willingness to pay level and whether the platform allows a recommendation for using of the drug...
October 18, 2016: Läkartidningen
Hiroko Kitahara, Mariko Hirai, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition...
October 21, 2016: Oncology Reports
Edgar Teddy Quispe-Soto, Gloria M Calaf
Global cancer burden increased to 14.1 million new cases in 2012; and breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Curcumin is the major bioactive ingredient extracted from the rhizome of the plant Curcuma longa (turmeric). Paclitaxel is a microtubule-stabilizing agent originally isolated from the bark of Taxus brevifolia. Curcumin and paclitaxel were evaluated with two human breast cancer cell lines as the luminal MCF-7 and the basal-like MDA-MB-231 that are either positive or negative for hormonal receptors estrogen receptor, progesterone receptor and HER2, respectively...
October 19, 2016: International Journal of Oncology
Bryan H Norman, Jeff S McDermott
The neurotrophin nerve growth factor (NGF) has been implicated as a key mediator of chronic pain. NGF binds the tropomysin receptor kinase A (TrkA) and p75, resulting in the activation of downstream signaling pathways that have been linked to pro-nociception. While anti-NGF antibodies have demonstrated analgesia both preclinically and in patients, the mechanism of action of these agents remains unclear. We describe ligands targeting NGF, its receptors, and downstream/related targets. This Perspective highlights large and small molecule approaches to targeting the NGF-TrkA pathway both extra- and intracellularly...
October 25, 2016: Journal of Medicinal Chemistry
P Roldan-Ramos, L A Reyes-Figueroa, J Rumia, E Martinez-Lizana, A Donaire, M Carreno-Martinez
AIM: To describe clinical results and complications derived from vagal nerve stimulation therapy in drug resistant epileptic patients unsuitable for other surgical treatments, since the first implant in an epilepsy national referral centre. PATIENTS AND METHODS: A retrospective analysis of the patients implanted in our centre was held. Data related to baseline characteristics of their epilepsy and therapy complications was collected. RESULTS: 32 new implants in 31 patients are included, mean age of 34 years, 29...
November 1, 2016: Revista de Neurologia
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
Kai Ma, Ruirui Xing, Ti-Feng Jiao, Guizhi Shen, Chengjun Chen, Junbai Li, Xuehai Yan
Self-assembling peptide-based materials are playing an important role in fabricating drug delivery carriers, however, they are often limited by several challenges, such as precise structure modulation, desirable nanoscale size and sufficient circulation lifetime in the body. To address this issue, herein one type of injectable dipeptide-based nanocarriers with well-modulated size and structure has been developed by adjusting glutaraldehyde (GA) assisted cationic dipeptide (CDP) assembly. After loading a model photosensitive drug (Ce6) and further decorating CDP nanoparticles (NPs) with heparin polymers (Hep), the desired dipeptide-based NPs are achieved with average diameter of 100 nm and surface charge of -25 mV, which are favorable for the enhanced permeability and retention effects...
October 25, 2016: ACS Applied Materials & Interfaces
Y Ilan
BACKGROUND: The systemic immune system plays a role in inflammation and fibrogenesis associated with non-alcoholic steatohepatitis (NASH) and has become a potential target for drug development. In particular, the gut immune system has been suggested as a means for generating signals that can target the systemic immune system. AIM: To describe seven novel methods being developed for the treatment of NASH that target the gut immune system for alleviation of the systemic inflammatory response, including oral administration of fatty-liver-derived proteins, anti-CD3 antibodies, tumour necrosis factor fusion protein, anti-lipopolysaccharide antibodies, glucosylceramide, delayed-release mercaptopurine, and soy-derived extracts...
October 24, 2016: Alimentary Pharmacology & Therapeutics
Long Pan, Dun-Chen Yao, Yu-Zhong Yu, Bing-Jun Chen, Sheng-Jie Li, Gui-He Hu, Chang Xi, Zi-Hui Wang, Jian-Hua Li, Jie Long, Yong-Sheng Tu
The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Vellingiri Balachandar, Venkatesan Dhivya, Mohan Gomathi, Subramaniam Mohanadevi, Balasubramanian Venkatesh, Bharathi Geetha
Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs...
2016: Stem Cell Investigation
Paola De Cicco, Elisabetta Panza, Giuseppe Ercolano, Chiara Armogida, Giuseppe Sessa, Giuseppe Pirozzi, Giuseppe Cirino, John L Wallace, Angela Ianaro
Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs). They consist of a traditional NSAID to which an H2S-releasing moiety is covalently attached. We have recently demonstrated that H2S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H2S-releasing derivative of naproxen, ATB-346 [2-(6- methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H2S...
October 21, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Daull Philippe, Feraille Laurence, Barabino Stefano, Cimbolini Nicolas, Antonelli Sophie, Mauro Virgine, Garrigue Jean-Sébastien
Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0...
October 21, 2016: Experimental Eye Research
Cristina Prat, Alicia Lacoma
BACKGROUND: Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of resistance and the emergence of opportunistic pathogens that substitute the indigenous microbiota. METHODS: This review explores the major challenges and lines of research to adequately establish the clinical role of bacteria and the indications for antimicrobial treatment, and reviews novel therapeutic approaches...
October 2016: International Journal of Infectious Diseases: IJID
Dale Fisher, Paul Wicks, Zaheer-Ud-Din Babar
The development of new therapies has a rich history, evolves quickly with societal trends, and will have an exciting future. The last century has seen an exponential increase in complex interactions between medical practitioners, pharmaceutical companies, governments and patients. We believe technology and societal expectations will open up the opportunity for more individuals to participate as information becomes more freely available and inequality less acceptable. Corporations must recognize that usual market forces do not function ideally in a setting where health is regarded as a human right, and as modern consumers, patients will increasingly take control of their own data, wellbeing, and even the means of production for developing their own treatments...
October 25, 2016: BMC Medicine
Guang-Hui Ma, Yan Ye, Dan Zhang, Xin Xu, Pei Si, Jian-Long Peng, Yong-Long Xiao, Rui-Yuan Cao, Yu-Ling Yin, Jing Chen, Lin-Xiang Zhao, Yu Zhou, Wu Zhong, Hong Liu, Xiao-Min Luo, Li-Li Chen, Xu Shen
Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3C(pro) in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3C(pro) inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3C(pro). The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21...
October 11, 2016: European Journal of Medicinal Chemistry
Sara Westrøm, Tina B Bønsdorff, Nasir Abbas, Øyvind S Bruland, Thora J Jonasdottir, Gunhild M Mælandsmo, Roy H Larsen
BACKGROUND: Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. METHODS AND RESULTS: A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences...
2016: PloS One
Amalia Vartanian, Maria Baryshnikova, Olga Burova, Dariya Afanasyeva, Vsevolod Misyurin, Alexander Belyаvsky, Zoya Shprakh
The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug...
October 21, 2016: Melanoma Research
Emmanuel Fortier, Maryam Alavi, Julie Bruneau, Michelle Micallef, Jacinta Perram, Sanjeev Sockalingam, Adrian J Dunlop, Annie C Balcomb, Carolyn A Day, Carla Treloar, Nicky Bath, Paul S Haber, Gregory J Dore, Jason Grebely
OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia)...
October 21, 2016: Journal of Addiction Medicine
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