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Drug treatment

Abdulkadir Kocak, Ismail Erol, Muslum Yildiz, Hatice Can
Developing small compound based drugs targeting the β-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme...
October 17, 2016: Journal of Molecular Graphics & Modelling
Patrizia Carrieri, Antoine Vilotitch, Sandra Nordmann, Caroline Lions, Laurent Michel, Marion Mora, Alain Morel, Gwenaelle Maradan, Bruno Spire, Perrine Roux
BACKGROUND: Patients receiving buprenorphine who are poor responders can continue to commit drug-related offences. Switching them from buprenorphine to methadone may result in reduced criminal behaviour. We compared self-reported offences and incarceration before and after starting methadone treatment of patients switching from buprenorphine (PSB) and maintenance treatment incident users (MIU). METHODS: Data on offences, incarceration and other information, were obtained via a telephone interview...
October 19, 2016: International Journal on Drug Policy
Kelly Adamson, Lois Jackson, Jacqueline Gahagan
A complex array of intersecting social contextual factors are known to influence safer and/or unsafe practices among people who inject drugs. However, less is known about the social contextual factors that may specifically influence injection practices for young people who inject drugs. In this qualitative study, we explored with young people, ages 18-29, living in an urban centre in Nova Scotia, Canada, their perceptions and experiences of the social contextual factors that influence their safer and/or unsafe injection practices...
October 19, 2016: International Journal on Drug Policy
Elizabeth Hammond, Emma Shu, Karagin Sawchuk, Yvonne Myal, Afshin Raouf, Thomas Klonisch, Sabine Hombach-Klonisch, Etienne Leygue, Sam Kung, Janice Safneck, Michael Mowat, Wayne Xu, Leigh Murphy, Marshall Pitz
BACKGROUND: Few descriptive epidemiological studies on the incidence, treatment and survival can accurately reflect a whole population. Manitoba, Canada has an accurate cancer registry, a drug information program network and a breast screening program since 1995. This combined with a stable population provides true population data that can accurately describe the region. METHODS: Using a retrospective cohort design all Breast Cancer cases were obtained from 2004-2010 (N=5399) and grouped by Intrinsic sub-type...
October 19, 2016: Cancer Epidemiology
Kara J Walters, Anna Meador, John A Galdo, Katharine Ciarrocca
Coagulation disorders account for a high incidence of death in the U.S. due to stroke, myocardial infarction, and venous thromboembolism. In the past few years, numerous agents have been brought to market for the treatment of thromboembolism or prevention of thromboembolism. Similar to warfarin, these agents can cause bleeding disorders, which may exacerbate dental care treatment plans. This literature review examines the newer agents for the treatment of thromboembolism disorders, common side effects and drug interactions, the specific medical conditions each agent treats, and the dental perspective on how to medically management patients prescribed these medications...
October 22, 2016: Special Care in Dentistry
Jeannine Coburn, Jamie Harris, Alexander D Zakharov, Jennifer Poirier, Naohiko Ikegaki, Andre Kajdacsy-Balla, Monika Pilichowska, Alexander V Lyubimov, Hiroyuki Shimada, David L Kaplan, Bill Chiu
Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multi-cycle chemotherapies, resulting in short- and long-term toxicities. Here we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin, or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Louisa Gilbert, Tina Jiwatram-Negron, Danil Nikitin, Olga Rychkova, Tara McCrimmon, Irena Ermolaeva, Nadejda Sharonova, Aibek Mukambetov, Timothy Hunt
INTRODUCTION AND AIMS: Intimate partner violence (IPV) and other forms of gender-based violence (GBV) are serious public health threats among women who use drugs or engage in binge drinking in Kyrgyzstan. This study aimed to evaluate the feasibility and preliminary effects of a two-session IPV and GBV screening, brief intervention and referral to treatment model (WINGS) with HIV counselling and testing for women who use drugs or engage in binge drinking in Kyrgyzstan, using a pre/post-design...
October 22, 2016: Drug and Alcohol Review
Junsik Park, Minsuk Kwon, Eui-Cheol Shin
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development...
October 21, 2016: Archives of Pharmacal Research
Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
Paolo Girardi, Roberto Brugnoli, Giovanni Manfredi, Gabriele Sani
Lithium has been a gold standard in the treatment of bipolar disorder (BD) for several decades. Despite a general reduction in the use of lithium over the past several years, it is effective in the management of both manic and depressive episodes in BD and continues to be recommended as a first-line mood stabilizer. This review provides an overview of the pharmacology of lithium and highlights its clinical profile in the management of BD, focusing on the potential advantages of prolonged-release (PR) versus immediate-release (IR) formulations of lithium...
October 21, 2016: Drugs in R&D
Wilfried Dinh, Barbara Albrecht-Küpper, Mihai Gheorghiade, Adriaan A Voors, Michael van der Laan, Hani N Sabbah
Adenosine exerts a variety of physiological effects by binding to cell surface G-protein-coupled receptor subtypes, namely, A1, A2a, A2b, and A3. The central physiological role of adenosine is to preclude tissue injury and promote repair in response to stress. In the heart, adenosine acts as a cytoprotective modulator, linking cardiac function to metabolic demand predominantly via activation of adenosine A1 receptors (A1Rs), which leads to inhibition of adenylate cyclase activity, modulation of protein kinase C, and opening of ATP-sensitive potassium channels...
October 22, 2016: Handbook of Experimental Pharmacology
Daniel Nichol, Mark Robertson-Tessi, Peter Jeavons, Alexander R A Anderson
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself...
October 21, 2016: Genetics
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Eun-Young Nam, Sun Ah Kim, Heejung Kim, Su-Hyun Kim, Jae-Hyun Han, Ju-Hee Lee, Dong-Il Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. AIM OF THE STUDY: In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure...
October 18, 2016: Journal of Ethnopharmacology
Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP)...
October 18, 2016: Acta Biomaterialia
Danielle L Brunjes, Adam Castano, Autumn Clemons, Jonah Rubin, Mathew S Maurer
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques...
October 18, 2016: Journal of Cardiac Failure
Yuzuki Kanda, Miho Okada, Rina Ikarashi, Eri Morioka, Takashi Kondo, Masayuki Ikeda
Clozapine (Clz) and olanzapine (Olz) are second generation (atypical) antipsychotics, used widely for treating schizophrenia and bipolar disorder. These drugs share multiple sites of actions, however their mechanisms remain incompletely understood. Here, we analyzed the effects of these drugs on primary cultures of rat cortical astrocytes and C6 glioma cells using fura-2-based Ca(2+) imaging. C6 cells, but not cortical astrocytes, express the serotonin 2A receptor subtype, which couples to phospholipase C. Clz (1μM) significantly blocked serotonin-induced Ca(2+) transients in C6 cells, consistent with known antagonistic actions of Clz...
October 18, 2016: Neuroscience Letters
Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein Extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Yufeng Li, Zheng Li, Dan Wang, Xiang Zhang, Jia Li, Sher Ali, Jingze Lu, Hao Zong, Xiaolan Xu
Insulin-stimulated GLUT4 translocation from GLUT4 storage vesicles (GSVs) to the plasma membrane (PM) constitutes a key process for blood glucose control. Therefore, compounds that could promote GLUT4 translocation into the PM represent potential drugs for the treatment of diabetes. In this research, we screened for agonists that induce GLUT4 translocation by using a novel pH-sensitive fluorescent probe, insulin-regulated aminopeptidase (IRAP)-mOrange2. We identified as well as validated one agonist, staurosporine, from a 64,000 compound library...
October 18, 2016: Biochemical and Biophysical Research Communications
Luisa Iacovelli, Luisa Di Menna, Daniel Peterlik, Christina Stangl, Rosamaria Orlando, Gemma Molinaro, Antonio De Blasi, Valeria Bruno, Giuseppe Battaglia, Peter J Flor, Nicole Uschold-Schmidt, Ferdinando Nicoletti
We studied the interaction between mGlu7 and α1-adrenergic receptors in heterologous expression systems, brain slices, and living animals. L-2-Amino-4-phosphonobutanoate (L-AP4), and l-serine-O-phosphate (L-SOP), which activate group III mGlu receptors, restrained the stimulation of polyphosphoinositide (PI) hydrolysis induced by the α1-adrenergic receptor agonist, phenylephrine, in HEK 293 cells co-expressing α1-adrenergic and mGlu7 receptors. The inibitory action of L-AP4 was abrogated by (i) the mGlu7 receptor antagonist, XAP044; (ii) the C-terminal portion of type-2 G protein coupled receptor kinase; and (iii) the MAP kinase inhibitors, UO126 and PD98059...
October 18, 2016: Neuropharmacology
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