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https://www.readbyqxmd.com/read/29333777/-retrospective-analysis-of-adverse-drug-reactions-in-stomatology-hospital-from-2014-to-2016
#1
Li Jia, Wang Jianli, Zhao Ke, Zhao Shaofeng
OBJECTIVE: This study aims to investigate the characteristics and general rules of adverse drug reactions (ADR) in a 3A-grade stomatology hospital for safe and rational drug use in clinical stomatology. METHODS: We retrospectively analyzed 52 ADR cases (1∶1.36, males∶females) reported in the West China Hospital of Stomatology of Sichuan University from 2014 to 2016 in terms of gender and age distributions, drug categories, and clinical manifestations. RESULTS: Eight kinds of drugs and antibiotics were predominately used [24 cases, 46...
December 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/29332842/ligand-cascading-nano-delivery-devices-to-enable-multiscale-targeting-of-anti-neurodegenerative-therapeutics
#2
Adam Mullis, Benjamin William Schlichtmann, Balaji Narasimhan, Rebecca Cademartiri, Surya K Mallapragada
Neurodegenerative diseases are a debilitating set of conditions that affect a significant fraction of the world's population, and this fraction is expected to increase as the population ages. Many therapeutic strategies have been explored to treat the pathological mechanisms of neurodegenerative disease, but multiple sequential hurdles to central nervous system delivery, including the blood-brain barrier, diseased neuronal membranes, and the organelle barrier, make drug delivery challenging and necessitate the use of innovative strategies to target and cross each barrier...
January 15, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29332563/multi-target-directed-drugs-as-a-modern-approach-for-drug-design-towards-alzheimer-s-disease-an-update
#3
Matheus de Freitas Silva, Kris Simone Tranches Dias, Vanessa Silva Gontijo, Cindy Juliet Cristancho Ortiz, Claudio Viega
Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative disorder. Currently, no effective treatment is available and this is due to multiple factors involved in pathophysiology and severity of AD. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDL) strategy, has been used to develop a variety of hybrid compounds capable to act simultaneously in diverse biological targets. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29330855/getting-innovative-therapies-faster-to-patients-at-the-right-dose-impact-of-quantitative-pharmacology-towards-first-registration-and-expanding-therapeutic-use
#4
Satyaprakash Nayak, Oliver Sander, Nidal Al-Huniti, Dinesh de Alwis, Anne Chain, Marylore Chenel, Soujanya Sunkaraneni, Shruti Agrawal, Neeraj Gupta, Sandra A G Visser
Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy...
January 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29330437/a-computational-assay-of-estrogen-receptor-%C3%AE-antagonists-reveals-the-key-common-structural-traits-of-drugs-effectively-fighting-refractory-breast-cancers
#5
Matic Pavlin, Angelo Spinello, Marzia Pennati, Nadia Zaffaroni, Silvia Gobbi, Alessandra Bisi, Giorgio Colombo, Alessandra Magistrato
Somatic mutations of the Estrogen Receptor α (ERα) occur with an up to 40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged endocrine treatments. These polymorphisms are implicated in acquired resistance, disease relapse, and increased mortality rates, hence representing a current major clinical challenge. Here, multi-microseconds (12.5 µs) molecular dynamics simulations revealed that recurrent ERα polymorphisms (i. e. L536Q, Y537S, Y537N, D538G) (mERα) are constitutively active in their apo form and that they prompt the selection of an agonist (active)-like conformation even upon antagonists binding...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328649/phenylthiomethyl-ketone-based-fragments-show-selective-and-irreversible-inhibition-of-enteroviral-3c-proteases
#6
Robert Schulz, Amira Atef, Daniel Becker, Franziska Gottschalk, Carolin Tauber, Stefan Wagner, Christoph Arkona, Atef A Abdel-Hafez, Hassan H Farag, Jörg Rademann, Gerhard Wolber
Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29326367/organic-anion-transporter-2-mediates-hepatic-uptake-of-tolbutamide-a-cytochrome-p450-2c9-probe-drug
#7
Yi-An Bi, Sumathy Mathialagan, Laurie Tylaska, Myra Fu, Julie Keefer, Anna Vildhede, Chester Costales, A David Rodrigues, Manthena Varma
Tolbutamide is primarily metabolized by cytochrome P450 (CYP)2C9, and thus, frequently applied as a clinical probe substrate for CYP2C9 activity. However, there is a marked discrepancy in the in vitro-in vivo extrapolation of its metabolic clearance implying potential for additional clearance mechanisms. The goal of this study was to evaluate the role of hepatic uptake transport in the pharmacokinetics of tolbutamide and identify the molecular mechanism thereof. Transport studies using singly-transfected cells expressing six major hepatic uptake transporters showed that tolbutamide is a substrate to organic anion transporter (OAT)2 alone -- with transporter affinity (Km) of 19...
January 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29322778/using-genome-sequence-to-enable-the-design-of-medicines-and-chemical-probes
#8
Alicia J Angelbello, Jonathan L Chen, Jessica L Childs-Disney, Peiyuan Zhang, Zi-Fu Wang, Matthew D Disney
Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics...
January 11, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29322474/pharmacovigilance-in-developing-countries-part-ii-a-path-forward
#9
Shaimaa Elshafie, Anne Marie Roberti, Iman Zaghloul
In recent years, attention to pharmacovigilance has gained momentum in developing countries, however awareness of, and policies or systems for pharmacovigilance in most developing countries still lags sharply behind developed countries. This article proposes different strategies to encourage the introduction and sustain the advancement of robust pharmacovigilance systems in developing countries. To this end, this article seeks to accomplish the ultimate goal of pharmacovigilance in a developing country context; ensuring patient safety and promoting safe and rational use of drugs...
January 10, 2018: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/29318114/the-impact-of-the-national-essential-medicines-policy-on-rational-drug-use-in-primary-care-institutions-in-jiangsu-province-of-china
#10
Jianqian Chao, Jiangyi Gu, Hua Zhang, Huanghui Chen, Zhenchun Wu
Background: Essential medicine policy is a successful global health policy to promote rational drug use. The aim of this study was to evaluate the impact of the National Essential Medicines Policy (NEMP) on the rational drug use in primary care institutions in Jiangsu Province of China. Methods: In this exploratory study, a multistage, stratified, random sampling was used to select 3400 prescriptions from 17 primary care institutions who implemented the NEMP before (Jan 2010) and after the implementation of the NEMP (Jan 2014)...
January 2018: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29314262/adverse-drug-reactions-of-analgesic-medicines-analysis-of-the-romanian-pharmacovigilance-database
#11
Irina Cazacu, Roxana Stroe, Roxana Dondera, Cristina Mogosan, Françoise Haramburu, Annie Fourrier-Réglat, Felicia Loghin
The results of national safety studies are essential for decision-making at the regulatory level and have also educational implications for prescribing patterns. The aim of the present study was to analyze the ADRs of analgesic medicines spontaneously reported to Pharmacovigilance and Risk Management Service of the Romanian National Agency for Medicines and Medical Devices between 2011 and 2015. For the 71 reports, patients had a mean age of 39.8 years; 60.6% of patients were female, 38% male and 1.4% were unknown...
January 4, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29314183/fixed-dosing-of-intravenous-tocilizumab-in-rheumatoid-arthritis-results-from-a-population-pharmacokinetic-analysis
#12
Carla Bastida, Virginia Ruiz-Esquide, Mariona Pascal, Aurelia H M de Vries Schultink, Jordi Yagüe, Raimon Sanmartí, Alwin D R Huitema, Dolors Soy
AIM: Intravenous tocilizumab is currently dosed on body weight although a weak correlation between body weight and clearance has been described. The aim of the study was to assess the current dosing strategy and provide a scientific rational for dosing using a modeling and simulation approach. METHODS: Serum concentrations and covariates were obtained from intravenous tocilizumab treated subjects at a dose of 4, 6 or 8 mg every 28 days. A population pharmacokinetic analysis was performed using nonlinear mixed effects modeling...
January 4, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29313444/poly-adp-ribose-polymerase-inhibitors-in-the-management-of-ovarian-cancer
#13
Maurie Markman
There is considerable interest and enthusiasm within the clinical gynecologic oncology community regarding the potential for poly (ADP-ribose) polymerase inhibitors to play a critically relevant role in the management of epithelial ovarian cancer and particularly (although not exclusively) in the setting of known mutations in the BRCA gene. This review will briefly highlight the biological rational for the use of poly (ADP-ribose) polymerase inhibitors in this malignancy, followed by summary of currently available clinical data supporting the delivery of agents approved by the US Food and Drug Administration for non-investigative use...
January 2018: Women's Health
https://www.readbyqxmd.com/read/29311258/molecular-mechanisms-of-cutis-laxa-and-distal-renal-tubular-acidosis-causing-mutations-in-v-atpase-a-subunits-atp6v0a2-and-atp6v0a4
#14
Sally Esmail, Norbert Kartner, Yeqi Yao, Joo Wan Kim, Reinhart A F Reithmeier, Morris F Manolson
The a subunit is the largest of 15 different subunits that make up the vacuolar H+-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1-a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation...
January 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29306991/asthma-and-medicines-long-term-side-effects-monitoring-and-dose-titration
#15
REVIEW
Satnam Kaur, Varinder Singh
Asthma is a major pediatric respiratory morbidity requiring long-term management. A thorough knowledge of long-term medication side-effects in children is, thus, essential for every physician dealing with childhood asthma. Establishing diagnosis and initiating treatment is just a beginning of the journey. Ongoing monitoring is an essential component of comprehensive asthma management programme. Monitoring includes not only assessment of asthma control but also checking for adherence to treatment, technique of inhaler device use, associated co-morbities, if any, and potential environmental exposure...
January 6, 2018: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29305983/learning-how-to-use-iam-chromatography-for-predicting-permeability
#16
Giuseppe Ermondi, Maura Vallaro, Giulia Caron
The interest for IAM (Immobilized Artificial Membranes) chromatography in the prediction of drug permeability is increasing. Here we firstly set-up a dataset of 253 molecules including neutral and ionized drugs and few organic compounds for which we either measured or retrieved from the literature IAM.PC.DD2 log KwIAM data. Then we applied block relevance (BR) analysis to extract from PLS models the relative contribution of intermolecular forces governing log KwIAM and Δlog KwIAM (a combined descriptor calculated from log KwIAM)...
January 3, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29303950/cns-drug-development-lessons-learned-part-4-the-role-of-brain-circuitry-and-genes-tasimelteon-as-an-example
#17
Sheldon H Preskorn
This is the fourth in a series of columns discussing the rational and targeted development of drugs to affect specific central nervous system (CNS) circuits in specific ways based on knowledge gained by molecular biology and the human genome project. The first column in this series described 6 CNS drugs with novel mechanisms of action developed over the last 25 years. The second column discussed differences between syndromic diagnoses as exemplified by the third through the fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM III through DSM-5) and the new approach to psychiatric diagnoses championed by the National Institute of Mental Health in their Research Domain Criteria Initiative...
November 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/29301937/cyclipostins-and-cyclophostin-analogs-inhibit-the-antigen-85c-from-mycobacterium-tuberculosis-both-in-vitro-and-in-vivo
#18
Albertus Viljoen, Matthias Richard, Phuong Chi Nguyen, Patrick Fourquet, Luc Camoin, Rishi R Paudal, Giri R Gnawali, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan, Mickael Blaise, Laurent Kremer
An increasing prevalence of cases of drug-resistant tuberculosis requires the development of more efficacious chemotherapies. We previously reported the discovery of a new class of Cyclipostins and Cyclophostin (CyC) analogs exhibiting potent activity against Mycobacterium tuberculosis both in vitro and in infected macrophages. Competitive labeling/enrichment assays combined with MS have identified several serine or cysteine enzymes in lipid and cell wall metabolism as putative targets of these CyC compounds...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29299350/non-clinical-models-for-neurodegenerative-diseases-therapeutic-approach-and-drug-validation-in-animal-models
#19
Caridad Ivette Fernandez, Jessica López, Lázara Martinez
In 2016, 19.8% of the Cuban population was aged 60 or over. As a result, age-associated degenerative diseases and other diseases have become priority targets from a prophylactic, diagnostic and therapeutic perspective. As a result, the Cuban biomedical scientific community has addressed its basic, preclinical and epidemiological research in order to rise up to the challenge. A firm step in this direction has been the international congress "State of the art in non-clinical models for neurodegenerative diseases" which has brought together preclinical and clinical researchers, technicians and regulatory staff members from different countries to review the state of the art in neurodegenerations, find unifying ideas, objectives and collaborations or partnership...
December 2017: Behavioral Sciences
https://www.readbyqxmd.com/read/29297286/exploration-of-charge-states-of-balanol-analogues-acting-as-atp-competitive-inhibitors-in-kinases
#20
Ari Hardianto, Muhammad Yusuf, Fei Liu, Shoba Ranganathan
BACKGROUND: (-)-Balanol is an ATP mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is a tumour promoter, PKC isozymes act as tumour promoters or suppressors, depending on the cancer type. In particular, PKCε is frequently implicated in cancer promotion, making it a potential target for anticancer drugs. To improve isozyme selectivity of balanol, exhaustive structural and activity relationship (SAR) studies have been performed in the last two decades, but with limited success...
December 28, 2017: BMC Bioinformatics
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