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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
Ross D Blundell, Simon J Williams, Samantha D M Arras, Jessica L Chitty, Kirsten L Blake, Daniel J Ericsson, Nidhi Tibrewal, Jurgen Rohr, Y Q Andre E Koh, Ulrike Kappler, Avril A B Robertson, Mark S Butler, Matthew A Cooper, Bostjan Kobe, James A Fraser
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C...
September 9, 2016: ACS Infectious Diseases
Marloes A M Janssen, Peter P Koopmans, Roy P C Kessels
The objectives of the current study were to examine cognitive decline in relation to psychological wellbeing, HIV disease and treatment characteristics and baseline variables over a one-year period of time in a group of HIV-infected patients on long term cART with undetectable viral load in comparison to a HIV-negative control group. Eighty-two of 95 patients and 43 of 55 controls who completed a baseline assessment for the Art-NeCo study underwent a follow-up neuropsychological assessment. A repeated-measure general linear model analysis was performed to compare the performance at follow-up in comparison to baseline between the patients and controls...
October 17, 2016: AIDS and Behavior
Kaname Uno, Katsunori Iijima, Yasuhiko Abe, Tomoyuki Koike, Yasushi Takahashi, Nobuyuki Ara, Tooru Shimosegawa
PURPOSE: Endoscopic diagnosis of gastric cancer (GC) that emerges after eradication of Helicobacter pylori may be affected by unique morphological changes. Using comprehensive endoscopic imaging, which can reveal biological alterations in gastric mucosa after eradication, previous studies demonstrated that Congo red chromoendoscopy (CRE) might clearly show an acid non-secretory area (ANA) with malignant potential, while autofluorescence imaging (AFI) without drug injection or dyeing may achieve early detection or prediction of GC...
September 2016: Journal of Gastric Cancer
Daniel V Mogford, Rebecca J Lawrence
Aims and method To investigate the burden of medical comorbidity in a population receiving in-patient treatment for drug and alcohol problems. All patients admitted over a 6-month period were included in the data-set. We recorded diagnostic information on admission that allowed the calculation of predicted 10-year survival using a previously validated comorbidity index. Results Despite the majority of the sample having a predicted 10-year survival chance of greater than 75%, a sizeable minority (16.7%) are carrying a high burden of medical comorbidity, with a predicted 10-year survival chance of less than 50%...
October 2016: BJPsych Bulletin
Xueying Tan, Jingbo Hu
Sustained and controlled pellets are considered as one of the ideal dosage forms. Due to the large coverage area of pellets, loaded drugs can be absorbed completely in the body and bioavailability is improved correspondingly. Coated pellets-containing tablet is a special oral formulation consisting of various pellets with different release rate. Desired rate of drug release rate can be achieved by adjusting the proportion of pellets. However, this formulation faces strict requirements in the process of preparation...
September 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Racha Fadlallah, Fadi El-Jardali, Farah Annan, Hayat Azzam, Elie A Akl
BACKGROUND: A recent systematic review suggested that drug registrations and onsite quality inspections may be effective in reducing the prevalence of counterfeit and substandard drugs. However, simply replicating the most effective interventions is problematic, as it denotes implementing the intervention without further adaptation. OBJECTIVE: The aim was to systematically review the evidence beyond effectiveness for systems-level interventions to combat or prevent drug counterfeiting...
2016: Pharmaceutical Medicine
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
Claudia Balducci, Angelisa Frasca, Margherita Zotti, Pietro La Vitola, Emanuela Mhillaj, Emanuele Grigoli, Martina Iacobellis, Federica Grandi, Massimo Messa, Laura Colombo, Monica Molteni, Luigia Trabace, Carlo Rossetti, Mario Salmona, Gianluigi Forloni
[Background] Amyloid-β oligomers (AβO) are species mainly involved in the synaptic and cognitive dysfunction in Alzheimer's disease. Although their action has been described mainly at neuronal level, it is now clear that glial cells govern synaptic activity in their resting state, contributing to new learning and memory establishment. In contrast, when activated, they may lead to synaptic and cognitive dysfunction. Using a reliable acute AβO-mediated mouse model of AD, we explored whether the memory alteration AβOs induce relies on the activation of glial cells, and if Toll-like receptor 4 (TLR4), pivotal in the initiation of an immune response, is involved...
October 14, 2016: Brain, Behavior, and Immunity
Nicola D Thompson, Lisa LaPlace, Lauren Epstein, Deborah Thompson, Ghinwa Dumyati, Cathleen Concannon, Gail Quinlan, Tory Witten, Linn Warnke, Ruth Lynfield, Meghan Maloney, Richard Melchreit, Nimalie D Stone
OBJECTIVES: To describe the prevalence and epidemiology of antimicrobial use (AU) in nursing home residents. DESIGN: One-day point prevalence survey. SETTING AND PARTICIPANTS: Nine nursing homes in four states; 1,272 eligible residents. MEASUREMENT: Frequency of antimicrobials prescribed, drug name, start date, duration, route, rationale, and treatment site. AU prevalence per 100 residents overall and by resident characteristic...
October 14, 2016: Journal of the American Medical Directors Association
N A Giraldo, P Amariles, M Monsalve, M J Faus
BACKGROUND: Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. OBJECTIVE: The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS...
September 23, 2016: Research in Social & Administrative Pharmacy: RSAP
Sophie E Walker, Aurélie Papilloud, Damien Huzard, Carmen Sandi
Aggressive behavior is not uniform, including proactive and reactive forms of aggression. Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is frequently associated with abnormal aggression. Here, we review the rodent literature in order to assess whether developmental abnormalities in the HPA axis can be causally linked with the emergence of abnormal aggression. We examine studies that involve genetic models and life challenges (e.g., early life stress, drug exposure) that course with developmental alterations in the HPA axis...
October 14, 2016: Neuroscience and Biobehavioral Reviews
Angela W Dymond, Colin Howes, Christine Pattison, Karen So, Gabriella Mariani, Mark Savage, Stuart Mair, Gill Ford, Paul Martin
PURPOSE: Selumetinib (AZD6244, ARRY-142886), an oral mitogen activated kinase 1/2 inhibitor, is in clinical development for the treatment of a variety of different tumor types. Herein, we report a study that determined the distribution, metabolism, and excretion of selumetinib in healthy male volunteers. METHODS: In this open-label, single-center, Phase I clinical trial, 6 subjects received a single 75-mg dose of [(14)C]-selumetinib. Blood and excreta samples were collected for pharmacokinetic and radiometric analyses...
October 14, 2016: Clinical Therapeutics
Axel C Mühlbacher, Susanne Bethge, Anika Kaczynski
BACKGROUND: Cardiovascular disease is one of the most common causes of death worldwide, with many individuals having experienced acute coronary syndrome (ACS). How patients with a history of ACS value aspects of their medical treatment have been evaluated rarely. The aim of this study was to determine patient priorities for long-term drug therapy after experiencing ACS. METHODS: To identify patient-relevant treatment characteristics, a systematic literature review and qualitative patient interviews were conducted...
October 18, 2016: International Journal of Technology Assessment in Health Care
Yang Yang, Ben-Quan Wu, Yan-Hong Wang, Yun-Feng Shi, Jin-Mei Luo, Jun-Hui Ba, Hui Liu, Tian-Tuo Zhang
Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments...
October 18, 2016: Immunopharmacology and Immunotoxicology
Félix Hernández, Sara Castiglioni, Adrian Covaci, Pim de Voogt, Erik Emke, Barbara Kasprzyk-Hordern, Christoph Ort, Malcolm Reid, Juan V Sancho, Kevin V Thomas, Alexander L N van Nuijs, Ettore Zuccato, Lubertus Bijlsma
The analysis of illicit drugs in urban wastewater is the basis of wastewater-based epidemiology (WBE), and has received much scientific attention because the concentrations measured can be used as a new non-intrusive tool to provide evidence-based and real-time estimates of community-wide drug consumption. Moreover, WBE allows monitoring patterns and spatial and temporal trends of drug use. Although information and expertise from other disciplines is required to refine and effectively apply WBE, analytical chemistry is the fundamental driver in this field...
October 17, 2016: Mass Spectrometry Reviews
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
Malihe Hassanzadeh, Kowsar Bagherzadeh, Massoud Amanlou
Nowadays the ability to prediction of complex behavior rationally based on the computational approaches has been a successful technique in drug discovery. In the present study interactions of a new series of hybrids, which were made by linking colchicine as a tubulin inhibitor and suberoylanilide hydroxamic acid (SAHA) as a HDAC inhibitor, with HDAC8 and HDAC1 were investigated and compared. This research has been facilitated by the availability of experimental information besides employing docking methodology as well as classical molecular dynamics simulations and binding free energy calculation were performed...
October 7, 2016: Journal of Molecular Graphics & Modelling
Julie Latimer, Stephen Ling, Ian Flaherty, Marianne Jauncey, Allison M Salmon
BACKGROUND: Fentanyl is a powerful analgesic, the prescription of which has increased markedly in recent years. The emergence of the drug at the Sydney Medically Supervised Injecting Centre (MSIC) warranted a retrospective clinical audit to assess the risk of fentanyl overdose in comparison with other opioids, in the context of a drug consumption room. METHOD: Heroin, fentanyl or other prescription opioids (PO) injections resulting in overdose were audited (September 1, 2012 and August 31, 2015)...
October 14, 2016: International Journal on Drug Policy
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