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drug AND interaction

Hwa-Ping Feng, Zifang Guo, Lisa L Ross, Iain Fraser, Deborah Panebianco, Patricia Jumes, Christine Fandozzi, Luzelena Caro, Jennifer Talaty, Joanne Ma, Eric Mangin, Xiaobi Huang, William L Marshall, Joan R Butterton, Marian Iwamoto, Wendy W Yeh
Background: Elbasvir/grazoprevir is a once-daily fixed-dose combination therapy for the treatment of chronic HCV infection, including HCV/HIV coinfection. Objectives: To evaluate the pharmacokinetic interaction of elbasvir and grazoprevir with raltegravir or dolutegravir. Methods: Three open-label trials in healthy adult participants were conducted. In the raltegravir trials, participants received a single dose of raltegravir 400 mg, a single dose of elbasvir 50 mg or grazoprevir 200 mg, and raltegravir with either elbasvir or grazoprevir...
December 12, 2018: Journal of Antimicrobial Chemotherapy
Polyanna Dos Santos Negreiros, Douglas Soares da Costa, Valdelânia Gomes da Silva, Izabela Borges de Carvalho Lima, Daniel Barbosa Nunes, Francisca Beatriz de Melo Sousa, Thiago de Souza Lopes Araújo, Jand Venes Rolim Medeiros, Rosimeire Ferreira Dos Santos, Rita de Cássia Meneses Oliveira
Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE2 in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6...
December 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Daniel Real, Stefan Hoffmann, Darío Leonardi, Claudio Salomon, Francisco M Goycoolea
Triclabendazole is a poorly-water soluble (0.24 μg/mL) compound classified into the Class II/IV of the Biopharmaceutical Classification System. It is the drug of choice to treat fascioliasis, a neglected parasitic disease worldwide disseminated. Triclabendazole is registered as veterinary medicine and it is only available for human treatment as 250 mg tablets. Thus, the aim of this work was to develop novel drug delivery systems based on nanotechnology approaches. The chitosan-based nanocapsules and nanoemulsions of triclabendazole were fully characterized regarding their particle size distribution, polydispersity index and zeta potential, in-vitro release and stability in biological media...
2018: PloS One
Mark E Cooper, Vlado Perkovic, Per-Henrik Groop, Berthold Hocher, Uwe Hehnke, Thomas Meinicke, Audrey Koitka-Weber, Sandra van der Walt, Maximilian von Eynatten
OBJECTIVE: Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial...
December 11, 2018: Journal of Hypertension
Youngdae Gwon, Seo-Hyun Kim, Hyun Tae Kim, Tae-In Kam, Jisu Park, Bitna Lim, Hyunju Cha, Ho-Jin Chang, Yong Rae Hong, Yong-Keun Jung
SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ1-42 ). Knockdown of LYN expression inhibited Aβ1-42 -induced neuronal cell death...
December 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Eric King-Fu Juang, Ine De Cock, Christina Keravnou, Madison K Gallagher, Sara B Keller, Ying Zheng, Michalakis Averkiou
Localized and targeted drug delivery can be achieved by the combined action of ultrasound, and microbubbles on the tumor microenvironment, likely through sonoporation and other therapeutic mechanisms not well understood. Here, we present a perfusable in vitro model with a realistic 3D geometry to study the interactions between microbubbles and the vascular endothelium in the presence of ultrasound. Specifically, a three-dimensional, endothelial-cell-seeded in vitro microvascular model was perfused with cell culture medium and microbubbles while sonicated by a single-element 1 MHz focused transducer...
December 12, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Yang Wang, Cecylia Severin Lupala, Haiguang Liu, Xubo Lin
Identifying drug binding sites and elucidating drug action mechanisms are important components in a drug discovery process. In this review, we briefly compared three different approaches (sequence-based methods, structure-based methods and probe-based molecular dynamics (MD) methods) to identifying drug binding sites, and concluded that probe-based MD methods are much more advantageous in dealing with flexible target macromolecules and digging out druggable macromolecule conformations for subsequent drug screening...
December 11, 2018: Current Topics in Medicinal Chemistry
Paola Chiodelli, Chiara Urbinati, Giulia Paiardi, Eugenio Monti, Marco Rusnati
Sialic acid is associated with glycoproteins and gangliosides of eukaryotic cells. It regulates various molecular interactions, being implicated in inflammation and cancer, where its expression is regulated by sialyltransferases and sialidases. Angiogenesis, the formation of new capillaries, takes place during inflammation and cancer, and represents the outcome of several interactions occurring at the endothelial surface among angiogenic growth factors, inhibitors, receptors, gangliosides and cell-adhesion molecules...
December 12, 2018: Future Medicinal Chemistry
Qiu-Yu Li, Hai-Yun Li
Biosensors based on the principle of surface plasmon resonance (SPR) are surface-sensitive optical devices used for monitoring biomolecular interactions at the sensor surface in real time without any labeling. It is used in a wide variety of areas including proteomics, clinical diagnosis, environmental monitoring, drug discovery, and food analysis. C-reactive protein (CRP) is a marker of inflammation, which undergoes conformation changes in local lesions, leading to the formation of mCRP. Autoantibodies against mCRP are frequently detected in systemic lupus erythematosus (SLE) and associated with disease activity and prognosis...
2019: Methods in Molecular Biology
Jeremy D King, John C Williams
Monoclonal antibodies (mAbs) are a major therapeutic modality. Grafting the meditope binding site onto mAbs, also known as meditope-enabling, can extend the usefulness of mAbs by providing an additional protein-protein interaction surface without altering the stability or antigen binding. We have previously used this site for attaching dyes, cytotoxic drugs, and entire proteins. Here, we provide a simple protocol for meditope-enabling mAbs, and verifying meditope and antigen binding using flow cytometry (FACS)...
2019: Methods in Molecular Biology
Woo-Jin Jeong, Jiyoon Bu, Luke J Kubiatowicz, Stephanie S Chen, YoungSoo Kim, Seungpyo Hong
Peptide-nanoparticle conjugates (PNCs) have recently emerged as a versatile tool for biomedical applications. Synergism between the two promising classes of materials allows enhanced control over their biological behaviors, overcoming intrinsic limitations of the individual materials. Over the past decades, a myriad of PNCs has been developed for various applications, such as drug delivery, inhibition of pathogenic biomolecular interactions, molecular imaging, and liquid biopsy. This paper provides a comprehensive overview of existing technologies that have been recently developed in the broad field of PNCs, offering a guideline especially for investigators who are new to this field...
December 12, 2018: Nano Convergence
Prakash P Praharaj, Prajna P Naik, Debasna P Panigrahi, Chandra S Bhol, Kewal K Mahapatra, Srimanta Patra, Gautam Sethi, Sujit Kumar Bhutia
The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Mitochondrial lipids, such as cardiolipin, ceramide, and sphingosine-1-phosphate, act as a mitophageal signal for the clearance of damaged mitochondria by interacting with mitophagic machinery as well as activate mitochondrial apoptosis via the release of cytochrome c into the cytoplasm...
December 11, 2018: Cellular and Molecular Life Sciences: CMLS
Lars Wiehemeier, Marian Cors, Oliver Wrede, Julian Oberdisse, Thomas Hellweg, Tilman Kottke
Stimuli-responsive microgels are colloidal particles and promising candidates for applications such as targeted drug delivery, matrices for catalysts, nanoactuators and smart surface coatings. To tailor the response, the architecture of microgels is of paramount importance with respect to these applications. Statistical copolymer microgels based on N-isopropylmethacrylamide (NiPMAM) and N-n-propylacrylamide (NnPAM) show a cooperative phase transition leading to a collapse at a specific temperature. Interestingly, some core-shell microgel particles reveal a linear response of the hydrodynamic radius with temperature...
December 12, 2018: Physical Chemistry Chemical Physics: PCCP
H Al-Samkari
Avatrombopag maleate (Doptelet; Dova Pharmaceuticals) is an oral, small-molecule second-generation thrombopoietin (TPO) receptor agonist under development for the treatment of thrombocytopenia. Recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease on the basis of the results of two phase III trials, it is currently under investigation for treatment of immune thrombocytopenia (two randomized trials demonstrating efficacy have already been completed), chemotherapy-induced thrombocytopenia and perioperative thrombocytopenia in patients undergoing major surgical procedures...
November 2018: Drugs of Today
Sudha Singh, Anvita Gupta Malhotra, Mohit Jha, Khushhali Menaria Pandey
Recently three FDA approved existing drugs, namely-Oseltamivir, Peramivir and Zanamivir, used against Neuraminidase (NA) for the inhibitory effect on the process of viral progeny release to inhibit infection. All NA subtypes has been divided into two groups (Group 1 and Group 2) based on phylogenetic study. Oseltamivir and Zanamivir drugs are designed for Group 2 NA but are also used against 2009 H1N1 NA that lies in Group 1. There is no specific drug available for H1N1 and, consequently, there is an urgent requirement for the same...
December 2018: Virusdisease
Saikou Y Bah, Collins Misita Morang'a, Jonas A Kengne-Ouafo, Lucas Amenga-Etego, Gordon A Awandare
Genomics and bioinformatics are increasingly contributing to our understanding of infectious diseases caused by bacterial pathogens such as Mycobacterium tuberculosis and parasites such as Plasmodium falciparum . This ranges from investigations of disease outbreaks and pathogenesis, host and pathogen genomic variation, and host immune evasion mechanisms to identification of potential diagnostic markers and vaccine targets. High throughput genomics data generated from pathogens and animal models can be combined with host genomics and patients' health records to give advice on treatment options as well as potential drug and vaccine interactions...
2018: Frontiers in Genetics
Jae-Ung Lee, Li-Kyung Kim, Je-Min Choi
The nuclear factor of activated T cells (NFAT) family of transcription factors, which includes NFAT1, NFAT2, and NFAT4, are well-known to play important roles in T cell activation. Most of NFAT proteins are controlled by calcium influx upon T cell receptor and costimulatory signaling results increase of IL-2 and IL-2 receptor. NFAT3 however is not shown to be expressed in T cells and NFAT5 has not much highlighted in T cell functions yet. Recent studies demonstrate that the NFAT family proteins involve in function of lineage-specific transcription factors during differentiation of T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh)...
2018: Frontiers in Immunology
Min Li, Ying Yang
Background: As one of the most invasive cutaneous carcinomas among all types of skin cancer, malignant melanoma remains a severe challenge in oncology and plastic surgery. Selective small-molecule inhibitors of V600E-mutant B-Raf (vemurafenib, for instance) have demonstrated satisfactory therapeutic efficacy in melanoma patients. However, acquired resistance during the period of drug administration has limited their clinical application. Materials and methods: In the present study, human melanoma cells with the B-RafV600E mutation were treated with the indicated concentrations of vemurafenib, quaternized chitosan, or a combination of vemurafenib and quaternized chitosan...
2018: OncoTargets and Therapy
Jie Yin, Karen Chapman, Lindsay D Clark, Zhenhua Shao, Dominika Borek, Qingping Xu, Junmei Wang, Daniel M Rosenbaum
The NK1 tachykinin G-protein-coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK1 R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK1 R (hNK1 R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK1 R are inhibitors for chemotherapy-induced nausea and vomiting (CINV)...
December 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Leandro José de Assis, Adriana Manfiolli, Eliciane Mattos, João H T Marilhano Fabri, Iran Malavazi, Ilse D Jacobsen, Matthias Brock, Robert A Cramer, Arsa Thammahong, Daisuke Hagiwara, Laure Nicolas Annick Ries, Gustavo Henrique Goldman
Aspergillus fumigatus mitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage compounds. Here we show that this process is dependent on cAMP-dependent protein kinase A (PKA) activity and regulated by the high-osmolarity glycerol response (HOG) MAPKs SakA and MpkC. These protein kinases are necessary for normal accumulation/degradation of trehalose and glycogen, and the lack of these genes reduces glucose uptake and glycogen synthesis...
December 11, 2018: MBio
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