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https://www.readbyqxmd.com/read/28644017/spectrally-undiscerned-isomers-might-lead-to-erroneous-determination-of-water-exchange-rates-of-paracest-eu-iii-agents
#1
Nevenka Cakić, Ben Tickner, Moritz Zaiss, David Esteban-Gómez, Carlos Platas-Iglesias, Goran Angelovski
We report a detailed study of the solution structure and water exchange rate of a Eu(III) complex with the cyclen-based ligand L(1), containing (S)-2-(2-acetamido)-3-(4-(trifluoromethyl)phenyl)propanoate pendant arms at positions 1 and 7 of the cyclen ring and acetylglycinate pendants at positions 4 and 10. The EuL(1) complex was characterized by a combination of NMR and luminescence spectroscopy and density functional theory (DFT) calculations. The chemical exchange saturation transfer (CEST) spectra obtained at different temperatures and saturation powers present a CEST signal attributed to the coordinated water molecule...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28643912/mouse-models-for-the-study-of-cranial-base-growth-and-anomalies
#2
REVIEW
S R Vora
The cranial base is a central and integral component of the cranioskeleton, yet little is known about its growth. Despite the dissimilarities between human and murine cranioskeletal form, mouse models are proving instrumental in studying craniofacial growth. The objectives of this review are to summarize recent findings from numerous mouse models that display growth defects in one or more cranial base synchondroses, with accompanying changes in chondrocyte cellular zones. Many of these models also display altered growth of the cranial vault and/or the facial region...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643430/platinum-containing-regimens-for-metastatic-breast-cancer
#3
REVIEW
Sam J Egger, Melina L Willson, Jenna Morgan, Harriet S Walker, Sue Carrick, Davina Ghersi, Nicholas Wilcken
BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. Most of these studies were conducted prior to the 'intrinsic subtype' era, and did not specifically focus on metastatic triple-negative breast cancers (mTNBCs). OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer...
June 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28643026/predictive-model-of-urinary-tract-infection-after-surgical-treatment-for-women-with-endometrial-cancer
#4
Hiroko Machida, Marianne S Hom, Anastasiya Shabalova, Brendan H Grubbs, Koji Matsuo
PURPOSE: The aim of the study was to identify risk factors associated with postoperative urinary tract infections (UTIs) following hysterectomy-based surgical staging in women with endometrial cancer. METHODS: This is a retrospective study utilizing an institutional database (2008-2016) of stage I-IV endometrial cancer cases that underwent hysterectomy-based surgery. UTIs occurring within a 30-day time period after surgery were examined and correlated to patient clinico-pathological demographics...
June 22, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28641893/recent-development-of-transition-metal-complexes-with-in-vivo-antitumor-activity
#5
Jia-Xin Liang, Hai-Jing Zhong, Guanjun Yang, Kasipandi Vellaisamy, Dik-Lung Ma, Chung-Hang Leung
The often severe side effects displayed by currently used platinum and ruthenium complexes have motivated researchers to design and develop transition metal-based anti-tumor agents with reduced toxicity. Distinct from organic anti-tumor drugs, transition metal complexes possess several properties that render them as promising scaffolds for anti-cancer drug discovery. While a vast number of metal complexes have been synthesized and reported to be promising and potent in vitro anticancer active compounds, fewer have shown efficacy in in vivo models...
June 16, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#6
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28641540/metallothionein-is-a-potential-therapeutic-strategy-for-amyotrophic-lateral-sclerosis
#7
Shin-Ichi Ono
Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 mice, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human mutant SOD1s...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#8
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641362/estimating-the-potential-cost-of-a-high-dose-immune-tolerance-induction-iti-therapy-relative-to-the-cost-of-a-combined-therapy-of-a-low-dose-iti-therapy-with-bypassing-agent-prophylaxis
#9
G Kenet, A Oladapo, J D Epstein, C Thompson, A Novack, D J Nugent
INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP...
June 22, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28641006/dft-simulation-of-structural-and-optical-properties-of-9-aminoacridine-half-sandwich-ru-ii-rh-iii-and-ir-iii-antitumoural-complexes-and-their-interaction-with-dna
#10
José Pedro Cerón-Carrasco, José Ruiz, Consuelo Vicente, Concepcion de Haro, Delia Bautista, Jose Zuniga, Alberto Requena
In this work, we use DFT-based methods to simulate the chemical structures, optical properties and interaction with DNA of a recently synthesized chelated CˆN 9-aminoacridine arene Ru (II) anticancer agent and two new closely related Rh(III) and Ir(III) complexes using DFT-based methods. Four chemical models and a number of theoretical approaches, which representatively include the PBE0, B97D, ωB97X, ωB97X-D, M06, and M06-L density functionals and the LANL2DZ, def2-SVP, def2- TZVP basis sets, are tested...
June 22, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28640692/comparison-of-gadolinium-concentrations-within-multiple-rat-organs-after-intravenous-administration-of-linear-versus-macrocyclic-gadolinium-chelates
#11
Robert J McDonald, Jennifer S McDonald, Daying Dai, Dana Schroeder, Mark E Jentoft, David L Murray, Ramanathan Kadirvel, Laurence J Eckel, David F Kallmes
Purpose To compare gadolinium tissue concentrations of multiple linear and macrocyclic chelates in a rat model to better understand the scope and extent of tissue deposition following multiple intravenous doses of gadolinium-based contrast agent (GBCA). Materials and Methods In this Institutional Animal Care and Use Committee-approved study, healthy rats received 20 intravenous injections of 2.5 mmol gadolinium per kilogram (gadolinium-exposed group) or saline (control group) over a 26-day period. Unenhanced T1 signal intensities of the dentate nucleus were measured from magnetic resonance (MR) images obtained prior to GBCA injection and 3 days after final injection...
June 19, 2017: Radiology
https://www.readbyqxmd.com/read/28640142/the-derivation-and-validation-of-a-simple-model-for-predicting-in-hospital-mortality-of-acutely-admitted-patients-to-internal-medicine-wards
#12
Ali Sakhnini, Walid Saliba, Naama Schwartz, Naiel Bisharat
Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639707/dressings-and-topical-agents-for-treating-pressure-ulcers
#13
REVIEW
Maggie J Westby, Jo C Dumville, Marta O Soares, Nikki Stubbs, Gill Norman
BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers...
June 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28639001/sanguinate%C3%A2-pegylated-carboxyhemoglobin-bovine-improves-cerebral-blood-flow-to-vulnerable-brain-regions-at-risk-of-delayed-cerebral-ischemia-after-subarachnoid-hemorrhage
#14
Rajat Dhar, Hemant Misra, Michael N Diringer
BACKGROUND: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease...
June 21, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#15
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28637361/antioxidant-activity-of-phenolic-compounds-from-extracts-of-eucalyptus-globulus-and-melaleuca-styphelioides-and-their-protective-role-on-d-glucose-induced-hyperglycemic-stress-and-oxalate-stress-in-nrk-49fcells
#16
Divya Ganesan, Eman Al-Sayed, Abhishek Albert, Eldho Paul, Abdel Nasser B Singab, Selvam Govindan Sadasivam, Luciano Saso
Phytochemicals serve as potential therapeutic agents for the prevention and treatment of diseases. In this study, we elucidate the renoprotective activity of compounds isolated from Eucalyptus globulus and Melaleuca styphelioides extracts in glucose- and oxalate-challenged NRK-49F cell model. The antioxidant potential of isolated compounds was evaluated based on their effect on antioxidant enzyme activities and lipid peroxidation levels. The results demonstrated that exposure of NRK-49F cells to glucose and oxalate stress augmented cell damage and attenuated antioxidant enzyme activities...
June 21, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#17
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637215/managerial-ownership-in-nursing-homes-staffing-quality-and-financial-performance
#18
Sean Shenghsiu Huang, John R Bowblis
Purpose of the Study: Ownership of nursing homes (NHs) has primarily focused broadly on differences between for-profit (FP), nonprofit (NFP), and government-operated facilities. Yet, among FPs, the understanding of detailed ownership structures at individual NHs is rather limited. Particularly, NH administrators may hold significant equity interests in their facilities, leading to heterogeneous financial incentives and NH outcomes. Through the principal-agent theory, this article studies how managerial ownership of individual facilities affects NH outcomes...
June 20, 2017: Gerontologist
https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#19
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636806/ph-dependent-general-base-catalyzed-activation-rather-than-isocyanate-liberation-may-explain-the-superior-anticancer-efficacy-of-laromustine-compared-to-related-1-2-bis-methylsulfonyl-1-2-chloroethyl-hydrazine-prodrugs
#20
P G Penketh, R A Finch, R Sauro, R P Baumann, E S Ratner, K Shyam
Laromustine (also known as cloretazine, onrigin, VNP40101M, 101M) is a prodrug of 90CE, a short-lived chloroethylating agent with anticancer activity. The short half-life of 90CE necessitates the use of latentiated prodrug forms for in vivo treatments. Alkylaminocarbonyl based prodrugs such as laromustine exhibit significantly superior in vivo activity in several murine tumor models compared to analogs utilizing acyl, and alkoxycarbonyl latentiating groups. The alkylaminocarbonyl prodrugs possess two exclusive characteristics: (i) they are primarily unmasked by spontaneous base catalyzed elimination; and (ii) they liberate a reactive carbamoylating species...
June 21, 2017: Chemical Biology & Drug Design
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