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Drug efficacy

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https://www.readbyqxmd.com/read/28239805/comparative-study-efficacy-of-closed-looptarget-controlled-infusion-of-cisatracurium-and-other-administration-methods-for-spinal-surgery-of-elderly-patients
#1
X-D Ma, J Yan, B-Z Dai, D-Q Kong, S-Y Du, B-P Li
OBJECTIVE: To observe the efficacy of traditional administration, continuous pump injection, and closed-loop target controlled infusion of cisatracurium to determine the optimal method of drug administration, and to establish the individualized and rational administration of muscle relaxants in elderly patients. PATIENTS AND METHODS: A total of 150 patients who underwent spinal surgery under tracheal intubation general anesthesia in our hospital from August 2013 to April 2015 were selected...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239674/dietary-supplementation-of-coenzyme-q10-plus-multivitamins-to-hamper-the-ros-mediated-cisplatin-ototoxicity-in-humans-a-pilot-study
#2
Felice Scasso, Andrea Elio Sprio, Luciano Canobbio, Chiara Scanarotti, Giorgio Manini, Giovanni Nicolao Berta, Anna Maria Bassi
Oxidative stress exerts major role in the pathogenesis of side effects of many antineoplastic drugs, including ototoxicity of cisplatin. In particular, increased levels of reactive oxygen species (ROS) represent one of the molecular mechanisms underlying the apoptosis of different types of hearing cells. Antioxidants and ROS scavengers may thus represent potential therapeutic options to prevent platinum-associated ototoxicity. The aim of this preliminary case-control study was to explore the efficacy of a dietary antioxidant supplement, in order to hamper the occurrences of ototoxicity in patients undergoing cisplatin chemotherapy...
February 2017: Heliyon
https://www.readbyqxmd.com/read/28239499/a-dual-case-of-peritonitis-and-central-nervous-system-infection-caused-by-nutritionally-variant-streptococcal-species
#3
Sussi Vivar, Jennifer E Girotto, Thomas S Murray
Nutritional variant streptococci (NVS) are difficult to identify bacteria that can cause invasive infections such as endocarditis and meningitis. NVS as a cause of peritonitis has not been routinely described. This case of NVS as the etiology of peritonitis associated with previous neurosurgery and ventriculoperitoneal (VP) shunt revision demonstrates its potential role as a significant pathogen in patients with peritonitis and VP shunts. Therapy consists of vancomycin plus a second agent but since there are no standards for susceptibility testing, clinical response remains the standard for determining the efficacy of treatment...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28239036/short-term-subcutaneous-fondaparinux-and-oral-edoxaban-for-acute-venous-thromboembolism
#4
Shinji Hisatake, Takayuki Kabuki, Shunsuke Kiuchi, Takashi Oka, Shintaro Dobashi, Takahiro Fujii, Yoshihiro Iwasaki, Takanori Ikeda
BACKGROUND: No studies have compared treatment efficacy between subcutaneous (SC) fondaparinux and oral edoxaban, which are categorized as factor Xa inhibitors, for venous thromboembolism (VTE) in the acute phase, and only a limited number of imaging-based quantitative studies have evaluated treatment.Methods and Results:In this open-label, randomized study, 50 patients with acute non-massive pulmonary embolism (PE) and/or deep-vein thrombosis (DVT) were assigned to fondaparinux or edoxaban groups...
February 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28238966/managing-lafora-body-disease-with-vagal-nerve-stimulation
#5
Mohamad A Mikati, Faysal Tabbara
A 17-year-old female, of consanguineous parents, presented with a history of seizures and cognitive decline since the age of 12 years. She had absence, focal dyscognitive, generalized myoclonic, and generalized tonic-clonic seizures, all of which were drug resistant. The diagnosis of Lafora body disease was made based on a compatible clinical, EEG, seizure semiology picture and a disease-causing homozygous mutation in the EPM2A gene. A vagus nerve stimulator (VNS) was inserted and well tolerated with a steady decrease and then stabilization in seizure frequency during the six months following insertion (months 1-6)...
February 22, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28238877/current-therapy-for-chronic-hepatitis-c-the-role-of-direct-acting-antivirals
#6
REVIEW
Guangdi Li, Erik De Clercq
One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status...
February 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28238876/ar-12-suppresses-dengue-virus-replication-by-down-regulation-of-pi3k-akt-and-grp78
#7
Hsin-Hsin Chen, Chien-Chin Chen, Yee-Shin Lin, Chiou-Feng Lin, Chia-Ling Chen, Chih-Peng Chang
Dengue virus (DENV) infection has become a public health issue of worldwide concern and is a serious health problem in Taiwan, yet there are no approved effective antiviral drugs to treat DENV. The replication of DENV requires both viral and cellular factors. Owing to the rapid mutation rate of viral factors, targeting host factors may serve as a more promising antiviral strategy. It has been known that up-regulation of PI3K/AKT signaling and GRP78 by DENV infection supports its replication. AR-12, a phase I trial completed anticancer drug, shows potent inhibitory activities on both PI3K/AKT signaling and GRP78 expression levels, and recently has been found to block the replication of several hemorrhagic fever viruses...
February 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28238870/clinical-considerations-for-optimal-use-of-the-polymyxins-a-focus-on-agent-selection-and-dosing
#8
REVIEW
Jason Pogue, Keith Kaye
Polymyxins have remained the drug of choice for treatment due to carbapenem-resistant Gram-negative bacilli. Unfortunately, the utility of these agents has been limited by a lack of pharmacokinetic understanding, a high toxicity rate, and an extremely narrow therapeutic index. Significant advancements have been achieved in the understanding of the polymyxins over the past decade, and have led to the recognition of several differences between available intravenous formulations. The purpose of this review is to discuss the implications of these differences, assess comparative efficacy and safety of the polymyxins, and provide recommendations for polymyxin dosing and selection...
February 23, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28238856/gemcitabine-kills-proliferating-endothelial-cells-exclusively-via-acid-sphingomyelinase-activation
#9
Albert J van Hell, Adriana Haimovitz-Friedman, Zvi Fuks, William D Tap, Richard Kolesnick
Gemcitabine is a widely-used anti-cancer drug with a well-defined mechanism of action in normal and transformed epithelial cells. However, its effect on endothelial cells is largely unknown. Acid sphingomyelinase (ASMase) is highly expressed in endothelial cells, converting plasma membrane sphingomyelin to pro-apoptotic ceramide upon activation by diverse stresses. In the current study, we investigated gemcitabine impact in primary cultures of endothelial cells. We find baseline ASMase increases markedly in bovine aortic endothelial cells (BAEC) as they transit from a proliferative to a confluent growth-arrested state...
February 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28238787/aptamer-based-liposomes-improve-specific-drug-loading-and-release
#10
Kevin Plourde, Rabeb Mouna Derbali, Arnaud Desrosiers, Céline Dubath, Alexis Vallée-Bélisle, Jeanne Leblond
Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes...
February 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28238742/molecular-signatures-order-the-potency-of-topically-applied-anti-inflammatory-drugs-in-atopic-dermatitis-patients
#11
Emma Guttman-Yassky, Benjamin Ungar, Kunal Malik, Daniel Dickstein, Maria Suprun, Yeriel D Estrada, Hui Xu, Xiangyu Peng, Margeaux Oliva, Dan Todd, Tord Labuda, Mayte Suarez-Farinas, Robert Bissonnette
BACKGROUND: Atopic Dermatitis (AD) presents a large unmet need for treatments with better safety and efficacy. To facilitate development of topical therapeutics, we need an efficient model for assessing different formulations and concentrations. The "plaque model" has been successfully implemented in psoriasis, another common inflammatory disease, to assess efficacy of topical treatments. This model has not been validated for AD, which has higher placebo responses and less stable lesions than psoriasis...
February 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28238727/testosterone-metabolism-of-equine-single-cyps-of-the-3a-subfamily-compared-to-the-human-cyp3a4
#12
S Vimercati, M Büchi, J Zielinski, N Peduto, M Mevissen
Cytochrome P450 enzymes (CYPs) are responsible for the phase I metabolism of drugs, xenobiotics and endogenous substances. Knowledge of single CYPs and their substrates is important for drug metabolism, helps to predict adverse effects and may prevent reduced drug efficacy in polypharmacy. In this study, three equine isoenzymes of the 3A subfamily, the equine flavoprotein NADPH-P450 oxidoreductase (POR), and the cytochrome b5 (CYB5) were cloned, sequenced and heterologously expressed in a baculovirus expression system...
February 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28238563/the-development-and-use-of-vascular-targeted-therapy-in-ovarian-cancer
#13
REVIEW
Dana M Chase, David J Chaplin, Bradley J Monk
Combination vascular-targeted therapies (VTTs) represent a promising approach for patients with platinum-resistant recurrent ovarian cancer (OC). VTTs include two mechanistically distinct classes of agents: anti-angiogenic agents (AAs) and vascular-disrupting agents (VDAs). AAs suppress growth of new tumor vasculature through inhibition of vascular endothelial growth factor (VEGF) and other pro-angiogenic molecules. Bevacizumab, a monoclonal antibody that binds to VEGF, has improved progression-free survival (PFS) when given with chemotherapy in patients with advanced OC...
February 23, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28238471/structural-basis-of-substrate-recognition-by-the-multidrug-resistance-protein-mrp1
#14
Zachary Lee Johnson, Jue Chen
The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 Å without any added substrate and a complex form at 3.3 Å with one of its physiological substrates, leukotriene C4...
February 22, 2017: Cell
https://www.readbyqxmd.com/read/28238302/the-effects-of-pure-potassium-channel-blocker-nifekalant-and-sodium-channel-blocker-mexiletine-on-malignant-ventricular-tachyarrhythmias
#15
Sou Otuki, Kanae Hasegawa, Hiroshi Watanabe, Goro Katsuumi, Nobue Yagihara, Kenichi Iijima, Akinori Sato, Daisuke Izumi, Hiroshi Furushima, Masaomi Chinushi, Yoshifusa Aizawa, Tohru Minamino
BACKGROUND: Patients with repetitive ventricular tachyarrhythmias - so-called electrical storm - frequently require antiarrhythmic drugs. Amiodarone is widely used for the treatment of electrical storm but is ineffective in some patients. Therefore, we investigated the efficacy of stepwise administration of nifekalant, a pure potassium channel blocker, and mexiletine for electrical storm. METHODS: This study included 44 patients with repetitive ventricular tachyarrhythmias who received stepwise therapy with nifekalant and mexiletine for electrical storm...
September 8, 2016: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28238223/glucose-lowering-agents-for-treating-pre-existing-and-new-onset-diabetes-in-kidney-transplant-recipients
#16
REVIEW
Clement Lo, Min Jun, Sunil V Badve, Helen Pilmore, Sarah L White, Carmel Hawley, Alan Cass, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes...
February 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28238186/effects-of-hallucinogens-on-neuronal-activity
#17
L Lladó-Pelfort, P Celada, M S Riga, E Troyano-Rodríguez, N Santana, F Artigas
Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. The present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive NMDA receptor (NMDA-R) antagonists and serotonergic hallucinogens. Our studies have focused on the mechanisms through which these agents alter cortical activity. Noncompetitive NMDA-R antagonists, such as phencyclidine (PCP) and MK-801 (dizocilpine), as well as the serotonergic hallucinogens DOI and 5-MeO-DMT, produce similar effects on cellular and population activity in prefrontal cortex (PFC); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0...
February 26, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28238145/high-accuracy-determination-of-cytotoxic-responses-from-graphene-oxide-exposure-using-imaging-flow-cytometry
#18
Sandra Vranic, Kostas Kostarelos
Graphene and other 2D materials have received increased attention in the biomedical field due to their unique properties and potential use as carriers for targeted drug delivery or in regenerative medicine. Before the exploitation of graphene-based materials in biomedicine becomes a reality, it is necessary to establish the full toxicological profile and better understand how the material interacts with cells and tissues. Because specific properties, such as flake size and surface chemistry, might determine whether graphene can achieve therapeutic efficacy without causing toxicity, it is important to develop highly accurate and reliable screening techniques to accurately assess the biocompatibility of different types of graphene-based materials...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28238139/photolabile-self-immolative-dna-drug-nanostructures
#19
Xuyu Tan, Ke Zhang
It is often desirable to simultaneously target different cellular pathways to improve the overall efficacy of a drug or to circumvent drug resistance in therapeutic treatments. Nucleic acid therapy has been considered attractive for such combination therapies due to its possible synergistic effects with traditional chemotherapy, especially for targets that do not yet have small molecule inhibitors. However, the co-delivery of nucleic acids and chemotherapeutics typically involves the use of inherently cytotoxic/immunogenic, polycationic carrier systems, for which the benefit is often overshadowed by adverse side effects...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28238138/dual-wavelength-triggered-gold-nanorods-for-anticancer-treatment
#20
Dennis B Pacardo, Frances S Ligler, Zhen Gu
Gold nanomaterials with light-responsive properties can be exploited as light-triggered delivery vehicles to enhance the therapeutic efficacy of anticancer drugs. Additionally, different wavelengths of light can be utilized to achieve the combined effects of light-triggered release of therapeutics and light-induced localized heating, which results in improved anticancer efficacy. Herein, we describe methods to develop gold nanorod (AuNR) complexes that provide drug delivery or photothermal therapy when activated by ultraviolet (UV) or near-infrared (NIR) wavelengths of light, respectively...
2017: Methods in Molecular Biology
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