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Drug efficacy

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https://www.readbyqxmd.com/read/28437722/effective-active-vaccination-against-methamphetamine-in-female-rats
#1
J D Nguyen, P T Bremer, C S Hwang, S A Vandewater, K C Collins, K M Creehan, K D Janda, M A Taffe
BACKGROUND: Immunotherapies directed against methamphetamine (MA) abuse have shown success in rodent models, however only a limited number of studies have investigated active vaccination in female mice and none in female rats. It is critical to determine if potential immunotherapeutic strategies generalize across sex, particularly for drugs that may produce significant sex-differences on behavioral or physiological endpoints. METHODS: Female Wistar rats were initially vaccinated with keyhole-limpet hemocyanin (KLH) or an anti-methamphetamine-KLH conjugate (MH6-KLH) three times over five weeks and implanted with radiotelemetry devices to assess locomotor activity and body temperature responses to MA...
April 14, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28437678/efficacy-safety-tolerability-and-price-of-newly-approved-drugs-in-solid-tumors
#2
REVIEW
Tristan A Barnes, Eitan Amir, Arnoud J Templeton, Susana Gomez-Garcia, Beatriz Navarro, Bostjan Seruga, Alberto Ocana
BACKGROUND: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. METHODS: Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis...
April 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#3
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28437610/long-acting-release-formulation-of-exendin-4-based-on-biomimetic-mineralization-for-type-2-diabetes-therapy
#4
Wei Chen, Guohao Wang, Bryant C Yung, Gang Liu, Zhiyong Qian, Xiaoyuan Chen
Exendin-4 has been clinically exploited for treating type 2 diabetes, but the short circulation half-life and multiple daily injections limit its widespread application with respect to poor patient compliance, low efficacy, and high treatment cost. In this study, a potent long-acting release system based on biomimetic mineralization was constructed for biocompatible and sustained exendin-4 delivery. Similar to natural biomineralization, exendin-4 can be mineralized to form nano-sized mineral solids by means of the reaction between acidic amino acid residues and calcium ions in a supersaturated environment with negligible influence on peptide bioactivity...
April 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28437539/safety-and-efficacy-of-antiviral-therapy-for-prevention-of-cytomegalovirus-reactivation-in-immunocompetent-critically-ill-patients-a-randomized-clinical-trial
#5
Nicholas J Cowley, Andrew Owen, Sarah C Shiels, Joanne Millar, Rebecca Woolley, Natalie Ives, Husam Osman, Paul Moss, Julian F Bion
Importance: Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective: To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014...
April 24, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28437452/enhanced-antibacterial-metabolite-production-through-the-application-of-statistical-methodologies-by-a-streptomyces-nogalater-niist-a30-isolated-from-western-ghats-forest-soil
#6
Jubi Jacob, Reshma Uma Rajendran, Syama Hari Priya, Jayamurthy Purushothaman, Dileep Kumar Bhaskaran Nair Saraswathy Amma
Streptomyces strains isolated from Nelliyampathy forest soil of Western Ghats, Kerala, India were evaluated for their antibacterial efficacy against two indicator pathogenic bacteria (Escherichia coli and Staphylococcus aureus). Among 140 strains tested, sixteen recorded potent antibacterial properties and were further screened against eleven bacterial pathogens. A strain identified as Streptomyces nogalater and designated as NIIST A30 exhibited maximum inhibition against all the test pathogens. Among the eight fermentation media tested, inorganic salts starch broth recorded the best for antibacterial production...
2017: PloS One
https://www.readbyqxmd.com/read/28437080/comparison-of-tumor-penetration-of-podophyllotoxin-carboxymethylcellulose-conjugates-with-various-chemical-compositions-in-tumor-spheroid-culture-and-in-vivo-solid-tumor
#7
Yang Yang, Aniruddha Roy, Yucheng Zhao, Elijus Undzys, Shyh-Dar Li
Polymer conjugation is an attractive approach for delivering insoluble and highly toxic drugs to tumors. However, most reports in the literature only disclose the optimal composition without emphasizing rational design or composition optimization to achieve maximized biological effects. In this study, we aimed to demonstrate that composition of a polymer conjugate would determine its physiochemical characteristics, tumor penetration and, ultimately, the in vivo efficacy. We also aimed to examine whether the tumor spheroid model could generate comparable results with the in vivo tumor model in terms of tumor penetration and efficacy of the various polymer conjugates...
April 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28437025/effectiveness-of-paracetamol-versus-ibuprofen-administration-in-febrile-children-a-systematic-literature-review
#8
Kaajal Narayan, Simon Cooper, Julia Morphet, Kelli Innes
AIM: The use of antipyretics to manage the febrile child is becoming increasingly popular. Paracetamol and ibuprofen are the most commonly used interventions to manage fever in children; however, there have been no comparative analyses. The aim of the study is to evaluate the evidence comparing paracetamol to ibuprofen in the treatment of fever in children. METHODS: A systematic review of randomised controlled trials investigating the administration of oral paracetamol and ibuprofen to reduce fever in children...
April 24, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/28436718/design-of-a-novel-curcumin-soybean-phosphatidylcholine-complex-based-targeted-drug-delivery-systems
#9
Jiajiang Xie, Yanxiu Li, Liang Song, Zhou Pan, Shefang Ye, Zhenqing Hou
Recently, the global trend in the field of nanomedicine has been toward the design of combination of nature active constituents and phospholipid (PC) to form a therapeutic drug-phospholipid complex. As a particular amphiphilic molecular complex, it can be a unique bridge of traditional dosage-form and novel drug delivery system. In thisarticle, on the basis of drug-phospholipid complex technique and self-assembly technique, we chose a pharmacologically safe and low toxic drug curcumin (CUR) to increase drug-loading ability, achieve controlled/sustained drug release and improve anticancer activity...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28436707/samhd1-protects-cancer-cells-from-various-nucleoside-based-antimetabolites
#10
Nikolas Herold, Sean G Rudd, Kumar Sanjiv, Juliane Kutzner, Julia Bladh, Cynthia B J Paulin, Thomas Helleday, J I Henter, Torsten Schaller
Recently, we demonstrated that sterile alpha motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemic (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Using an AML mouse model, we show here that wild type but not catalytically inactive SAMHD1 reduces ara-C treatment efficacy in vivo...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28436630/-clinical-investigation-on-transarterial-chemoembolization-with-indigenous-drug-eluting-beads-in-treatment-of-unresectable-hepatocellular-carcinoma
#11
Gang Chen, Ding Zhang, Yacao Ying, Zhifeng Wang, Wei Tao, Hao Zhu, Jingfeng Zhang, Zhiyi Peng
Objective: To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC). Methods: The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres (®)) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28436316/first-in-man-experience-of-self-expanding-nitinol-stents-combined-with-drug-coated-balloon-in-the-treatment-of-femoropopliteal-occlusive-disease
#12
Bibombe Patrice Mwipatayi, Kalpa Perera, Ali Daneshmand, Rhys Daniel, Jackie Wong, Shannon D Thomas, Sally A Burrows
Purpose The present study aimed to determine the safety and efficacy of a drug-coated balloon inflated within a thin-strut self-expanding bare-metal stent in patients with severe and complex femoropopliteal occlusive disease. Methods This prospective study used the Pulsar-self-expanding stent and Passeo-18 Lux drug-coated balloon in patients with severe and complex femoropopliteal occlusive disease. The primary endpoint was the 12-month primary patency, and the secondary endpoints included 24-month primary patency, assisted primary patency, secondary patency, and clinically associated target lesion revascularisation...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28436315/restenosis-after-carotid-artery-stenting
#13
Zhengze Dai, Gelin Xu
As a common etiology for ischemic stroke, atherosclerotic carotid stenosis has been targeted by vascular surgery since 1950s. Compared with carotid endarterectomy, carotid angioplasty and stenting (CAS) is almost similarly efficacious and less invasive. These advantages make CAS an alternative in treating carotid stenosis. However, accumulative evidences suggested that the long-term benefit-risk ratio of CAS may be decreased or even neutralized by the complications related to in-stent restenosis (ISR). Therefore, investigating the mechanisms and identifying the influential factors of ISR are of vital importance for improving the long-term outcomes of CAS...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28435985/elucidating-the-a%C3%AE-42-anti-aggregation-mechanism-of-action-of-tramiprosate-in-alzheimer-s-disease-integrating-molecular-analytical-methods-pharmacokinetic-and-clinical-data
#14
Petr Kocis, Martin Tolar, Jeremy Yu, William Sinko, Soumya Ray, Kaj Blennow, Howard Fillit, John A Hey
BACKGROUND: Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease...
April 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28435679/targeting-the-pro-inflammatory-factor-ccl2-mcp-1-with-bindarit-for-influenza-a-h7n9-treatment
#15
Stefan Wolf, Scott Johnson, Olivia Perwitasari, Suresh Mahalingam, Ralph A Tripp
Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435462/a-programmed-nanoparticle-with-self-adapting-for-accurate-cancer-cell-eradication-and-therapeutic-self-reporting
#16
Yingping Luo, Liwei Huang, Ye Yang, Xianfei Zhuang, Siyao Hu, Huangxian Ju, Bo-Yang Yu, Jiangwei Tian
To achieve the best therapeutic efficacy and good prognosis, the drugs necessitate tailored profiles of excellent spatiotemporal control and therapeutic monitoring. Here we introduce a programmed theranostic nanoparticle with self-adapting properties for tumor-specific systemic treatment, including stealthy surface to prolong circulation time in blood, surface charge-reversion for tumor targeting, receptor-mediated internalization to increase intracellular accumulation, "proton sponge effect" for controllable drug release and escape from endo/lysosome...
2017: Theranostics
https://www.readbyqxmd.com/read/28435458/phosphorylcholine-based-stealthy-nanocapsules-enabling-tumor-microenvironment-responsive-doxorubicin-release-for-tumor-suppression
#17
Gan Liu, Hsiang-I Tsai, Xiaowei Zeng, Yixiong Zuo, Wei Tao, Jun Han, Lin Mei
The efficient delivery of anticancer drugs into tumor tissues to improve therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug delivery system based on a stealthy nanocapsule was developed. This nanocapsule was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH-responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment (pH ~6...
2017: Theranostics
https://www.readbyqxmd.com/read/28435450/exome-sequencing-of-oral-squamous-cell-carcinoma-reveals-molecular-subgroups-and-novel-therapeutic-opportunities
#18
Shih-Chi Su, Chiao-Wen Lin, Yu-Fan Liu, Wen-Lang Fan, Mu-Kuan Chen, Chun-Ping Yu, Wei-En Yang, Chun-Wen Su, Chun-Yi Chuang, Wen-Hsiung Li, Wen-Hung Chung, Shun-Fa Yang
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features...
2017: Theranostics
https://www.readbyqxmd.com/read/28435447/a-unique-recombinant-fluoroprobe-targeting-activated-platelets-allows-in-vivo-detection-of-arterial-thrombosis-and-pulmonary-embolism-using-a-novel-three-dimensional-fluorescence-emission-computed-tomography-flect-technology
#19
Bock Lim, Yu Yao, Alex Lin-I Huang, May Lin Yap, Ulrike Flierl, Jathushan Palasubramaniam, Maria T K Zaldivia, Xiaowei Wang, Karlheinz Peter
Progress in pharmaceutical development is highly-dependent on preclinical in vivo animal studies. Small animal imaging is invaluable for the identification of new disease markers and the evaluation of drug efficacy. Here, we report for the first time the use of a three-dimensional fluorescence bioimager called FLuorescence Emission Computed Tomography (FLECT) for the detection of a novel recombinant fluoroprobe that is safe, easily prepared on a large scale and stably stored prior to scan. This novel fluoroprobe (Targ-Cy7) comprises a single-chain antibody-fragment (scFvTarg), which binds exclusively to activated-platelets, conjugated to a near-infrared (NIR) dye, Cy7, for detection...
2017: Theranostics
https://www.readbyqxmd.com/read/28435338/recommendations-for-optimizing-methotrexate-treatment-for-patients-with-rheumatoid-arthritis
#20
REVIEW
Alfonso E Bello, Elizabeth L Perkins, Randy Jay, Petros Efthimiou
Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration...
2017: Open Access Rheumatology: Research and Reviews
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