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Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment...
July 20, 2018: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Eman M Khedr, Bastawy Al Fawal, Ahmed Abdelwarith, Mostafa Saber, John C Rothwell
Tardive syndromes (TDS) typically manifest 3 months or later after exposure to antipsychotic drugs, and unfortunately have no satisfactory medical treatment. We explored the possibility of using therapeutic repetitive transcranial magnetic stimulation (rTMS). Twenty-six patients were allocated to receive real or sham rTMS over the hand/arm area of motor cortex (M1). Each received a daily total of 2000 rTMS pulses (20 Hz at 100% rMT: 1000 stimuli per hemisphere) for 10 consecutive days. Outcome was assessed using the Abnormal Involuntary Movement Scale (AIMS) and TMS measures of M1 excitability...
October 13, 2018: Journal of Neural Transmission
Wanli Yang, Jiaojiao Ma, Wei Zhou, Bo Cao, Xin Zhou, Hongwei Zhang, Qingchuan Zhao, Liu Hong, Daiming Fan
Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients' outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs...
October 13, 2018: Cellular and Molecular Life Sciences: CMLS
H F Miranda, P Poblete, F Sierralta, V Noriega, J C Prieto, R J Zepeda
Neuropathic pain is a complication of cancer and diabetes mellitus and the most commonly used drugs in the treatment of the diabetic neuropathic pain have only limited efficacy. The aim of this study was to evaluate the role of the biomarker interleukin-1beta (IL-1ß) in the pharmacological interaction of gabapentin with tramadol in a model of diabetic neuropathic pain. CF-1 male mice, pretreated with 200 mg/kg i.p. of streptozocin (STZ), were used and at day 3 and 7 were evaluated by the hot plate test and the spinal cord level of IL-1ß was determined...
October 13, 2018: Inflammopharmacology
Mark C Allenby, Nicki Panoskaltsis, Asma Tahlawi, Susana Brito Dos Santos, Athanasios Mantalaris
Traditional culture systems for human erythropoiesis lack microenvironmental niches, spatial marrow gradients and dense cellularity rendering them incapable of effectively translating marrow physiology ex vivo. Herein, a bio-inspired three-dimensional (3D) perfusion bioreactor was engineered and inoculated with unselected single donor umbilical cord blood mononuclear cells (CBMNCs). Functional stromal and hematopoietic environments supporting long-term erythropoiesis were generated using defined medium supplemented only with stem cell factor (SCF) and erythropoietin (EPO) at near physiological concentrations...
August 8, 2018: Biomaterials
Zhe Wang, Wei Sun, Zheng-Feng Lin, Rui Sun, Cheng-Ke Huang, Wei-Jian Ye, Yao-Yao Dong, Xiao-Dan Zhang, Rui-Jie Chen
Drug-drug interactions (DDIs) are thought to be associated with the inhibition of cytochrome P450 activities. The cocktail method with analysis of the metabolism of two or more probe drugs is used to determine CYP450 activities. In this study, we established a UHPLC-MS/MS method for simultaneous quantitation of four CYP450 probe drugs (phenacetin, omeprazole, metoprolol and midazolam) and their metabolites (acetaminophen, 5'-hydroxy omeprazole, α-hydroxy metoprolol and 1'-hydroxy midazolam) in rat plasma. Sample preparation by plasma protein precipitation was combined with a liquid-liquid extraction method...
October 4, 2018: Journal of Pharmaceutical and Biomedical Analysis
Luping Sha, Qinfu Zhao, Da Wang, Xian Li, Xiudan Wang, Xinyao Guan, Siling Wang
"Gate" engineered mesoporous silica nanoparticles (MSN) have been extensively applied in cancer theranostics. Due to the complexity of tumor development and progression, with chemotherapy alone, it has often been difficult to achieve a good therapeutic effect. Currently, it has been shown that the combination with photothermal therapy overcomes the shortcoming of chemotherapy. In most studies, the photothermal effect has proven to accelerate drug release from nanocarriers and ablate malignant cells directly, but the influence on the intracellular fate of nanocarriers remains unknown...
September 27, 2018: Journal of Colloid and Interface Science
Augustine Lalloz, Marie-Alexandrine Bolzinger, Jimmy Faivre, Pierre-Luc Latreille, Araceli Garcia Ac, Cyrielle Rakotovao, Jean-Michel Rabanel, Patrice Hildgen, Xavier Banquy, Stéphanie Briançon
We investigated the influence of nanoparticle (NP) surface composition on different aspects of skin delivery of a lipophilic drug: chemical stability, release and skin penetration. Cholecalciferol was chosen as a labile model drug. Poly(lactic acid) (PLA)-based NPs without surface coating, with a non-ionic poly(ethylene glycol) (PEG) coating, or with a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating were prepared using flash nanoprecipitation. Process was optimized to obtain similar hydrodynamic diameters...
October 10, 2018: International Journal of Pharmaceutics
Wint Wint Phoo, Zhenzhen Zhang, Melissa Wirawan, Edwin Chew Jun Chen, Chew Bing Liang Alvin, Jenny Kouretova, Torsten Steinmetzer, Dahai Luo
Zika virus NS2B-NS3 protease plays an essential role in viral replication by processing the viral polyprotein into individual proteins. The viral protease is therefore considered as an ideal antiviral drug target. To facilitate the development of protease inhibitors, we report three high-resolution co-crystal structures of bZiPro with peptidomimetic inhibitors composed of a P1-P4 segment and different P1' residues. Compounds 1 and 2 possess small P1' groups that are cleaved by bZiPro, which could be detected by mass spectrometry...
October 10, 2018: Antiviral Research
C N Miller, M J Caruso, H M Kamens
BACKGROUND: The initial response to nicotine is an important predictor of subsequent use. Multiple factors may alter this response including genetics and age of first use. Here we investigated the influence of age, genetics, and their interaction on nicotine sensitivity. We then examined whether these factors influence the relationship between initial behavioral responses and voluntary nicotine consumption in adulthood. METHODS: We measured initial nicotine responses, including nicotine-induced locomotor depression and hypothermia following an acute intraperitoneal injection (0, 0...
October 10, 2018: Neuroscience Letters
Ning Ji, Yuqi Yang, Chao-Yun Cai, Zi-Ning Lei, Jing-Quan Wang, Pranav Gupta, Suneet Shukla, Suresh V Ambudkar, Dexin Kong, Zhe-Sheng Chen
Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10...
October 10, 2018: Cancer Letters
Angelo Sala, Ewgenij Proschak, Dieter Steinhilber, G Enrico Rovati
Chronic inflammation and pain is a major global health problem, and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most frequently prescribed drugs and common option for the treatment of inflammatory pain. However, they have the potential to cause serious complications, such as gastrointestinal (GI) lesions, bleeding and cardiovascular (CV) problems. NSAIDs exert their anti-inflammatory, analgesic and anti-pyretic actions by inhibiting the cyclooxygenases (COX)-1 and COX-2, key enzymes of the arachidonic acid (AA) cascade...
October 10, 2018: Biochemical Pharmacology
Naiara Coelho Ximenes, Manuel Alves Dos Santos Júnior, Germana Silva Vasconcelos, Kátia Cilene Ferreira Dias, Mércia Marques Jucá, Aline Holanda Silva, Luzia Kalyne Almeida Moreira Leal, Glauce Socorro Barros Viana, Francisca Cléa Florenço de Sousa, Silvânia Maria Mendes Vasconcelos
Background Schizophrenia is a chronic mental disorder, characterized by positive, negative and cognitive symptoms. In general, several plants have shown activity in diseases related to the central nervous system (e.g., Erythrina velutina (EEEV), also known as "mulungu"). For this reason, we aimed to investigate the effects of standardized ethanol extract obtained from the stem bark of EEEV on the schizophrenia-like behaviors induced by ketamine (KET) administration. Methods Swiss mice were treated with KET (20 mg/kg, i...
October 12, 2018: Journal of Complementary & Integrative Medicine
Xue Feng, Usha Sambamoorthi, Kim Innes, Gregory Castelli, Traci LeMasters, Lianjie Xiong, Michael U Williams, Xi Tan
PURPOSE: This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF). METHODS: We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin...
October 12, 2018: Cardiovascular Drugs and Therapy
Niko M Perttila, Hanna Öhman, Timo E Strandberg, Hannu Kautiainen, Minna Raivio, Marja-Liisa Laakkonen, Niina Savikko, Reijo S Tilvis, Kaisu H Pitkälä
INTRODUCTION: No study has investigated how exercise modifies the effect of fall-related drugs (FRDs) on falls among people with Alzheimer's disease (AD). OBJECTIVE: The aim of this study was to investigate how exercise intervention and FRDs interact with fall risk among patients with AD. METHODS: In the FINALEX trial, community-dwelling persons with AD received either home-based or group-based exercise twice weekly for 1 year (n =129); the control group received normal care (n =65)...
October 13, 2018: Drugs & Aging
Jinxu Liu, Pauravi J Gandhi, Ratnamala Pavuluri, Gajanan P Shelkar, Shashank M Dravid
Cocaine exposure induces plasticity of glutamatergic synapses of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), which has been proposed to contribute to its addictive behavior. The mechanisms underlying cocaine-induced plasticity are not fully understood. The orphan glutamate delta-1 (GluD1) receptor is a member of the ionotropic glutamate receptor family but does not function as a typical ligand-gated ion channel. Instead it serves a synaptogenic function by interacting with presynaptic Neurexin protein...
October 12, 2018: Translational Psychiatry
Thanuja Gangi Setty, Jonathan C Mowers, Aaron G Hobbs, Shubha P Maiya, Sanaa Syed, Robert S Munson, Michael A Apicella, Ramaswamy Subramanian
The primary role of bacterial periplasmic binding proteins is sequestration of essential metabolites present at a low concentration in the periplasm and making them available for active transporters that transfer these ligands into the bacterial cell. The periplasmic binding proteins(SiaP) from the tripartite ATP-independent periplasmic (TRAP) transport system that transports mammalian host-derived sialic acids, have been well studied from different pathogenic bacteria, including Haemophilus influenzae , Fusobacterium nucleatum , Pasteurella multocida , and Vibrio cholerae SiaPs bind the sialic acid N-acetylneuraminic acid (Neu5Ac) with nanomolar affinity by forming electrostatic and hydrogen bonding interactions...
October 12, 2018: Journal of Biological Chemistry
Szymon W Manka, Carolyn A Moores
The development of cryo-electron microscopy (cryo-EM) allowed microtubules to be captured in their solution-like state, enabling decades of insight into their dynamic mechanisms and interactions with binding partners. Cryo-EM micrographs provide 2D visualization of microtubules, and these 2D images can also be used to reconstruct the 3D structure of the polymer and any associated binding partners. In this way, the binding sites for numerous components of the microtubule cytoskeleton-including motor domains from many kinesin motors, and the microtubule-binding domains of dynein motors and an expanding collection of microtubule associated proteins-have been determined...
October 12, 2018: Essays in Biochemistry
Shelby Barnett, Kayode Ogungbenro, Karelle Menochet, Hong Shen, Griffith W Humphreys, Aleksandra Galetin
Endogenous biomarkers can be clinically relevant tools for the assessment of transporter function in vivo and corresponding drug-drug interactions (DDIs). The aim of this study was to perform systematic evaluation of plasma data obtained for 20 endogenous molecules in the same healthy subjects (n=8-12) in the absence and presence of OATP inhibitor rifampicin (600mg s.d.). The extent of rifampicin DDI magnitude (AUCR), estimated fraction transported (fT) and baseline variability were compared across the biomarkers and relative to rosuvastatin and coproporphyrin I (CPI)...
October 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Sana Nafees, Syed Hassan Mehdi, Mohammad Zafaryab, Bushra Zeya, Tarique Sarwar, Moshahid Alam Rizvi
AIM OF THE STUDY: Rutin and Silibinin are active flavonoid compounds, well-known for possessing multiple biological activities. We have studied how Rutin and Silibinin in combination modulate wide range intracellular signaling cascades as evidenced by in-vitro research. Data obtained from preclinical studies provide evidence to be supportive to bridge basic and translational studies. METHODS: In this study, cytotoxic effect of Rutin and Silibinin individually and in combination on the viability of colon cancer cell line (HT-29) was revealed using the MTT assay...
October 9, 2018: Archives of Medical Research
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