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Drug combination

Maneea Eizadi Sharifabad, Tim Mercer, Tapas Sen
Liposome-capped core-shell mesoporous silica-coated superparamagnetic iron oxide nanoparticles called 'magnetic protocells' were prepared as novel nanocomposites and used for loading anticancer drug doxorubicin (DOX) for cellular toxicity study. Cytotoxicity of the magnetic protocells with or without DOX was tested in vitro on commercial MCF7 and U87 cell lines under alternating magnetic field. MCF7 cell line treated with the DOX-loaded nanoparticles under alternating magnetic field exhibited nearly 20% lower survival rate after 24 h compared with cells treated with free DOX and similarly, it was around 24% when applied to U87...
October 19, 2016: Nanomedicine
Nahid Shahabadi, Monireh Falsafi, Maryam Maghsudi
The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 10(4) L mol(-1) and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
Scott J Hughes, Leanne Barnard, Katayoun Mottaghi, Wolfram Tempel, Tetyana Antoshchenko, Bum Soo Hong, Abdellah Allali-Hassani, David Smil, Masoud Vedadi, Erick Strauss, Hee-Won Park
The potent antistaphylococcal activity of N-substituted pantothenamides (PanAms) has been shown to at least partially be due to the inhibition of Staphylococcus aureus's atypical type II pantothenate kinase (SaPanKII), the first enzyme of coenzyme A biosynthesis. This mechanism of action follows from SaPanKII having a binding mode for PanAms that is distinct from those of other PanKs. To dissect the molecular interactions responsible for PanAm inhibitory activity, we conducted a mini SAR study in tandem with the cocrystallization of SaPanKII with two classic PanAms (N5-Pan and N7-Pan), culminating in the synthesis and characterization of two new PanAms, N-Pip-PanAm and MeO-N5-PanAm...
September 9, 2016: ACS Infectious Diseases
Jyothi Padiadpu, Priyanka Baloni, Kushi Anand, MohamedHusen Munshi, Chandrani Thakur, Abhilash Mohan, Amit Singh, Nagasuma Chandra
The global mechanisms and associated molecular alterations that occur in drug-resistant mycobacteria are poorly understood. To address this, we obtain genomics data and then construct a genome-scale response network in isoniazid-resistant Mycobacterium smegmatis and apply a network-mining algorithm. Through this, we decipher global alterations in an unbiased manner and identify emergent vulnerabilities in resistant bacilli, of which redox response was prominent. Using phenotypic profiling, we find that resistant bacilli exhibit collateral sensitivity to several compounds that block antioxidant responses...
September 9, 2016: ACS Infectious Diseases
Rajkumar Bharatia, Manoj Chitale, Ganesh Narain Saxena, Raman Ganesh Kumar, Chikkalingaiah, Abhijit Trailokya, Kalpesh Dalvi, Suhas Talele
INTRODUCTION: Hypertension (HTN), being a major risk factor for cardiovascular diseases (CVDs), is an important issue of medical and public health. High blood pressure (BP) is ranked as the third most important risk factor for attributable burden of disease in south Asia (2010). Hypertension (HTN) exerts a substantial public health burden on cardiovascular health status and healthcare systems in India. Uncontrolled hypertension among adults with hypertension is associated with increased mortality...
July 2016: Journal of the Association of Physicians of India
Sanjay Prakash, Chaturbhuj Rathore
BACKGROUND: Trigeminal neuralgia (TN) has been described in association with various primary headache disorders. So far, no case of TN has been reported in association with hemicrania continua (HC). CASE REPORT: Here, we report two patients of hemicrania continua associated with TN (HC-tic syndrome). These patients had both headaches concurrently. Both patients responded to a combination of carbamazepine and indomethacin. The skipping or tapering of carbamazepine led to the recurrence of the neuralgic pain of TN...
October 18, 2016: Headache
Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Hanne Kuitunen, Susanna Tokola, Topi Siniluoto, Matti Isokangas, Eila Sonkajärvi, Seppo Alahuhta, Taina Turpeenniemi-Hujanen, Esa Jantunen, Tapio Nousiainen, Kaija Vasala, Outi Kuittinen
Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation...
October 17, 2016: Journal of Neuro-oncology
M E Cazzaniga, L Cortesi, A Ferzi, L Scaltriti, F Cicchiello, M Ciccarese, S Della Torre, F Villa, M Giordano, C Verusio, M Nicolini, A R Gambaro, L Zanlorenzi, E Biraghi, L Legramandi, E Rulli
PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS)...
October 17, 2016: Breast Cancer Research and Treatment
Shaiane Silva Tomazoni, Ernesto Cesar Pinto Leal-Junior, Lúcio Frigo, Rodney Capp Pallotta, Simone Teixeira, Patricia de Almeida, Jan Magnus Bjordal, Rodrigo Álvaro Brandão Lopes-Martins
No abstract text is available yet for this article.
October 1, 2016: Journal of Biomedical Optics
Kyung Sik Kang, Hyung Il Kim, Oh Hyun Kim, Kyoung Chul Cha, Hyun Kim, Kang Hyun Lee, Sung Oh Hwang, Yong Sung Cha
OBJECTIVE: Adverse cardiovascular events (ACVEs) account for a large proportion of the morbidities and mortalities associated with drug overdose emergencies. However, there are no published reports regarding outcomes of ACVEs associated with acute dapsone poisoning. Here, the authors retrospectively analyzed ACVEs reported within 48 hours of treatment in patients with acute dapsone poisoning and assessed the significance of ACVEs as early predictors of mortality. METHODS: Sixty-one consecutive cases of acute dapsone poisoning that were diagnosed and treated at a regional emergency center between 2006 and 2014 were included in the study...
March 2016: Clin Exp Emerg Med
Chan Joo Lee, Sungha Park
Despite improvements in hypertension awareness and treatment, the blood pressure (BP) control rate still remains at around 50%. One of the major determinants of low BP control results from therapeutic inertia of the physician and suboptimal compliance of the patients. Home BP self-measurement and monitoring improves patients' awareness and helps the management of hypertension. Recent technological advances are allowing for accurate measurement and telemonitoring of home BP, with a number of randomized clinical trials demonstrating the efficacy of telemonitoring for BP control...
September 2016: Pulse (Basel, Switzerland)
Angel R de Lera, A Ganesan
The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders...
2016: Clinical Epigenetics
Hetal Patel, Hiral Patel, Mukesh Gohel, Sanjay Tiwari
Context: Microcrystalline cellulose (MCC) is the most widely used excipient for the production of pellets but it retards the release of poorly water soluble drugs. Objective: The present investigation reports incorporation of camphor, cross carmellose sodium (CCS) and spray dried lactose (SDL) into MCC pellets to enhance the dissolution rate of telmisartan. Materials and methods: A full factorial design (3(2)) was used in the study. Concentration of camphor and CCS was selected as independent variables whereas percentage porosity and percentage drug release at 60 min were selected as dependent variables...
September 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Mélanie V Trudel, Antony T Vincent, Sabrina A Attéré, Myriam Labbé, Nicolas Derome, Alexander I Culley, Steve J Charette
The bacterium Aeromonas salmonicida subsp. salmonicida is a common pathogen in fish farms worldwide. Since the antibiotic resistance of this bacterial species is on the increase, it is important to have a broader view on this issue. In the present study, we tested the presence of known plasmids conferring multi-drug resistance as well as antibiotic resistance genes by a PCR approach in 100 Canadian A. salmonicida subsp. salmonicida isolates. Our study highlighted the dominance of the conjugative pSN254b plasmid, which confers multi-drug resistance...
October 18, 2016: Scientific Reports
Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Janis C Weeks, William M Roberts, Kristin J Robinson, Melissa Keaney, Jon J Vermeire, Joseph F Urban, Shawn R Lockery, John M Hawdon
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels...
September 15, 2016: International Journal for Parasitology, Drugs and Drug Resistance
E De Vlieghere, G Wagemans, S De Backer, Z Drebert, J Tommelein, Q Rousseau, B Weyn, M Van Troys, M Bracke, O De Wever
Cells change their morphology as a response to environmental cues. The quantitative evaluation of single cell spread on extracellular matrices, such as type I collagen, is a key tool in cancer research. Inherent to the manual scoring of cellular spread is inter-observer but also intra-observer variation. To overcome these problems, we have developed the Morphology Analysis Software (MAS). MAS scores phase-contrast images of cells on native type I collagen gels and identifies whether a cell has a spread or round morphology using a combination of four unique parameters such as the presence of a cellular extension, the cell area, the cell eccentricity and cell circularity...
October 14, 2016: Experimental Cell Research
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
Camille P Vaughan, Constance H Fung, Alison J Huang, Theodore M Johnson, Alayne D Markland
PURPOSE: Nocturia is associated with poor sleep quality; however, little is known about the relationship between nocturia and sleep quality across different workforce-relevant age groups of adults. This has implications for developing new treatment strategies that are well tolerated across populations. METHODS: We conducted a cross-sectional study involving merged data from the 2005-2006 and 2007-2008 waves of the National Health and Nutrition Examination Survey...
October 14, 2016: Clinical Therapeutics
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