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https://www.readbyqxmd.com/read/28945011/prediction-of-drug-drug-interaction-between-tacrolimus-and-principal-ingredients-of-wuzhi-capsule-in-chinese-healthy-volunteers-using-physiologically-based-pharmacokinetic-modelling
#1
Hongyan Zhang, Fengjiao Bu, Lei Li, Zheng Jiao, Guo Ma, Weimin Cai, Xiaomei Zhuang, Hai-Shu Lin, Jae-Gook Shin, Xiaoqiang Xiang
Schisantherin A and schisandrin A, the most abundant active ingredients of Wuzhi capsule, are known to inhibit tacrolimus metabolism by inhibiting CYP3A4/5. We aimed to predict the contribution of schisantherin A and schisandrin A to drug-drug interaction (DDI) between Wuzhi capsule and tacrolimus using physiologically-based pharmacokinetic (PBPK) modelling. Firstly, the inhibition mechanism of schisantherin A and schisandrin A on CYP3A4/5 were investigated. Thereafter, PBPK models of schisantherin A, schisandrin A and tacrolimus were established...
September 25, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28944496/the-unidirectional-hypoxia-activated-prodrug-oct1002-inhibits-growth-and-vascular-development-in-castrate-resistant-prostate-tumors
#2
Heather Nesbitt, Jenny Worthington, Rachel J Errington, Laurence H Patterson, Paul J Smith, Stephanie R McKeown, Declan J McKenna
BACKGROUND: OCT1002 is a unidirectional hypoxia-activated prodrug (uHAP) OCT1002 that can target hypoxic tumor cells. Hypoxia is a common feature in prostate tumors and is known to drive disease progression and metastasis. It is, therefore, a rational therapeutic strategy to directly target hypoxic tumor cells in an attempt to improve treatment for this disease. Here we tested OCT1002 alone and in combination with standard-of-care agents in hypoxic models of castrate-resistant prostate cancer (CRPC)...
September 24, 2017: Prostate
https://www.readbyqxmd.com/read/28943239/how-to-effectively-treat-acute-leukemia-patients-bearing-mll-rearrangements
#3
REVIEW
Dieter Steinhilber, Rolf Marschalek
Chromosomal translocations - leading to the expression of fusion genes - are well-studied genetic abberrations associated with the development of leukemias. Most of them represent altered transcription factors that affect transcription or epigenetics, while others - like BCR-ABL - are enhancing signaling. BCR-ABL has become the prototype for rational drug design, and drugs like Imatinib and subsequently improved drugs have a great impact on cancer treatments. By contrast, MLL-translocations in acute leukemia patients are hard to treat, display a high relapse rate and the overall survival rate is still very poor...
September 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28939378/polymorphic-phase-transitions-macroscopic-theory-and-molecular-simulation
#4
Jamshed Anwar, Dirk Zahn
Transformations in the solid state are of considerable interest, both for fundamental reasons and because they underpin important technological applications. The interest spans a wide spectrum of disciplines and application domains. For pharmaceuticals, a common issue is unexpected polymorphic transformation of the drug or excipient during processing or on storage, which can result in product failure. A more ambitious goal is that of exploiting the advantages of metastable polymorphs (e.g. higher solubility and dissolution rate) while ensuring their stability with respect to solid state transformation...
September 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28936830/-registration-of-30-026-cases-of-shenqi-fuzheng-injection-combined-with-other-drugs-in-real-world
#5
Lian-Xin Wang, Yan-Ming Xie, Qing-Hua Ai, Qian Feng
Prospective, multi-center, large-sample and registered design was used to analyze the drug combination features of Shenqi Fuzheng injection in the real world clinical application, and comprehend the drug combination in the real world. A total of 30 026 patients with the use of Shenqi Fuzheng injection were registered, where the chemical drugs were used for 57 436 times (accounting for 82.76%), and the Chinese patent medicines were used for 11 962 times (accounting for 17.24%), mainly including anti-acid drugs and anti-ulcer drugs, nutritional agent, immune enhancement agent, etc...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28934348/antimicrobial-resistance-in-clinical-escherichia-coli-isolates-from-poultry-and-livestock-china
#6
Afrah Kamal Yassin, Jiansen Gong, Patrick Kelly, Guangwu Lu, Luca Guardabassi, Lanjing Wei, Xiangan Han, Haixiang Qiu, Stuart Price, Darong Cheng, Chengming Wang
Poultry and livestock are the most important reservoirs for pathogenic Escherichia coli and use of antimicrobials in animal farming is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms. The aim of our study was to investigate antimicrobial resistance in E. coli isolated from food animals in Jiangsu, China. The disc diffusion method was used to determine susceptibility to 18 antimicrobial agents in 862 clinical isolates collected from chickens, ducks, pigs, and cows between 2004 and 2012...
2017: PloS One
https://www.readbyqxmd.com/read/28933302/smart-organic-inorganic-nanogels-for-activatable-theranostics
#7
Fangyuan Li, Zeyu Liang, Daishun Ling
Intelligent polymeric nanogels, with the rationally designed stimuli-responsive drug delivery and controlled drug release, have attracted considerable attention as an ideal nanoplatform for activatable therapy. On the other hand, functional inorganic nanomaterials are widely used as medical imaging agents due to their unique magnetic or optical properties. The construction of stimuli-responsive polymeric nanogels incorporating with functional inorganic nanomaterials inherits the excellent properties of both polymers and inorganic nanomaterials, consequently, the resulted organic-inorganic hybrid nanogels naturally exhibit stimuli-responsive multi-functionalities for both imaging and therapy...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28931578/lipid-topology-and-electrostatic-interactions-underpin-lytic-activity-of-linear-cationic-antimicrobial-peptides-in-membranes
#8
David J Paterson, Manlio Tassieri, Julien Reboud, Rab Wilson, Jonathan M Cooper
Linear cationic antimicrobial peptides are a diverse class of molecules that interact with a wide range of cell membranes. Many of these peptides disrupt cell integrity by forming membrane-spanning pores that ultimately lead to their death. Despite these peptides high potency and ability to evade acquired bacterial drug resistance, there is a lack of knowledge on their selectivity and activity mechanisms. Such an understanding would provide an informative framework for rational design and could lead to potential antimicrobial therapeutic targets...
September 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28930600/line-1-as-a-therapeutic-target-for-castration-resistant-prostate-cancer
#9
Nadine Houede, Pier Vincenzo Piazza, Philippe Pourquier
Prostate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28923870/associations-between-voriconazole-therapeutic-drug-monitoring-toxicity-and-outcome-in-liver-transplant-patients-an-observational-study
#10
Zahra Hashemizadeh, Parisa Badiee, Seyed Ali Malekhoseini, Hadi Raeisi Shahraki, Bita Geramizadeh, Hashem Montaseri
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28919737/bacterial-membrane-vesicles-as-novel-nanosystems-for-drug-delivery
#11
REVIEW
Sapna Jain, Jonathan Pillai
Bacterial membrane vesicles (BMVs) are closed spherical nanostructures that are shed naturally and ubiquitously by most bacterial species both in vivo and in vitro. Researchers have elucidated their roles in long-distance transport of a wide array of cargoes, such as proteins, toxins, antigens, virulence factors, microbicidal agents and antibiotics. Given that these natural carriers are important players in intercellular communication, it has been hypothesized that they are equally well attuned for transport and delivery of exogenous therapeutic cargoes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28918483/effects-of-multidisciplinary-teams-and-an-integrated-follow-up-electronic-system-on-clinical-pharmacist-interventions-in-a-cancer-hospital
#12
Muhammad Tahir Aziz, Tofeeq Ur Rehman, Sadia Qureshi, Sidrah Andleeb
Background The aim of drug therapy is to attain distinct therapeutic effects that not only improve patient's quality of life but also reduce the inherent risks associated with the therapeutic use of drugs. Pharmacists play a key role in reducing these risks by developing appropriate interventions. Whether to accept or reject the intervention made by the pharmacist is a relevant consultant's decision. Objective To evaluate the impact of electronic prompts and follow-up of rejected pharmacy interventions by clinical pharmacists in an in-patient setting...
September 16, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28916961/practical-computational-toolkits-for-dendrimers-and-dendrons-structure-design
#13
Nuno Martinho, Liana C Silva, Helena F Florindo, Steve Brocchini, Teresa Barata, Mire Zloh
Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures...
September 15, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28912448/a-general-reaction-mechanism-for-carbapenem-hydrolysis-by-mononuclear-and-binuclear-metallo-%C3%AE-lactamases
#14
María-Natalia Lisa, Antonela R Palacios, Mahesh Aitha, Mariano M González, Diego M Moreno, Michael W Crowder, Robert A Bonomo, James Spencer, David L Tierney, Leticia I Llarrull, Alejandro J Vila
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28911309/formulation-quality-control-and-safety-issues-of-nanocarriers-used-for-cancer-treatment
#15
Ismael D Bianco, Marcelo R Ceballos, Cristian Casado, Viviana G Dabbene, Carolina Rizzi, R Kiyomi Mizutamari
Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few...
June 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28911299/in-silico-models-for-nanomedicine-recent-developments
#16
Pietro Mascheroni, Bernhard Aribo Schrefler
Nanomedicine is a recent promising setting for the advancement of current medical therapies, in particular for cancer. Nanoparticle-mediated therapies are aimed to tackle extremely complex phenomena, involving different biochemical, mechanical and biophysical factors. Computational models can contribute to medical research by helping the understanding of biological mechanisms and by providing quantitative analyses. In this work, we report on computational models that address four main issues related to the use of nanoparticles in anti-cancer therapies, namely the delivery of nanoparticles, their uptake by cells, the release of drugs from nano-platforms and nanoparticle-based therapeutics...
April 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#17
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28905963/coarse-grained-molecular-dynamics-studies-of-the-structure-and-stability-of-peptide-based-drug-amphiphile-filaments
#18
Myungshim Kang, Honggang Cui, Sharon M Loverde
Peptide-based supramolecular filaments, in particular filaments self-assembled by drug amphiphiles (DAs), possess great potential in the field of drug delivery. These filaments possess one hundred percent drug loading, with a release mechanism that can be tuned based on the dissociation of the supramolecular filaments and the degradation of the DAs [Cheetham et al., J. Am. Chem. Soc., 2013, 135(8), 2907]. Recently, much attention has been drawn to the competing intermolecular interactions that drive the self-assembly of peptide-based amphiphiles into supramolecular filaments...
September 14, 2017: Soft Matter
https://www.readbyqxmd.com/read/28904942/a-simple-but-accurate-method-for-evaluating-drug-resistance-in-infectious-hcvcc-system
#19
Jian-Rui Li, Wen-Jing Li, Jun-Jun Cheng, Meng-Hao Huang, Zhou-Yi Wu, Chen-Chen Jiang, Hu Li, Jin-Hua Chen, Xiao-Qin Lv, Biao Dong, Jian-Dong Jiang, Zong-Gen Peng
Use of direct-acting antivirals sometimes causes viral drug resistance, resulting in inefficiency in treated patients in real-world practice. Therefore, how to rapidly and accurately evaluate drug resistance is an urgent problem to be solved for rational use and development of antivirals in the future. Here, we aim to develop a new method by which we can evaluate easily but effectively whether a drug will still be efficient in the future treatment in infectious hepatitis C virus cell culture system. HCV-infected Huh7...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904920/antimicrobial-susceptibility-pattern-of-extended-spectrum-beta-lactamases-producing-organisms-isolated-in-a-tertiary-care-hospital-bangladesh
#20
Mohammad Jobayer, Zeenat Afroz, Sultana Shazeda Nahar, Ayesha Begum, Shahin Ara Begum, S M Shamsuzzaman
CONTEXT: Infection caused by extended-spectrum beta-lactamases (ESBL) producing organism is a major problem regarding antibiotic resistance. AIMS: The aim of this study was to find out the antibiogram of ESBL producing organisms isolated from various samples. SETTINGS AND DESIGN: This cross-sectional study was carried out in the Department of Microbiology of a Tertiary Care Hospital, Dhaka, Bangladesh from January to June 2014. SUBJECTS AND METHODS: One Hundred and seventy-nine ESBL producing Gram-negative organisms detected phenotypically by double-disc synergy test were enrolled in this study...
July 2017: International Journal of Applied and Basic Medical Research
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