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https://www.readbyqxmd.com/read/29775937/design-synthesis-and-biological-evaluation-of-a-series-of-novel-2-benzamide-4-6-oxy-n-methyl-1-naphthamide-pyridine-derivatives-as-potent-fibroblast-growth-factor-receptor-fgfr-inhibitors
#1
Manman Wei, Xia Peng, Li Xing, Yang Dai, Ruimin Huang, Meiyu Geng, Ao Zhang, Jing Ai, Zilan Song
Starting from the phase II clinical FGFR inhibitor lucitanib (2), we conducted a medicinal chemistry approach by opening the central quinoline skeleton coupled with a scaffold hopping process thus leading to a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives. Compound 25a was identified to show selective and equally high potency against FGFR1/2 and VEGFR2 with IC50 values less than 5.0 nM. Significant antiproliferative effects on both FGFR1/2 and VEGFR2 aberrant cancer cells were observed...
May 15, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775127/glycemic-control-and-its-associated-factors-among-diabetes-mellitus-patients-at-ayder-comprehensive-specialized-hospital-mekelle-ethiopia
#2
Seifu Mideksa, Sintayehu Ambachew, Belete Biadgo, Habtamu Wondifraw Baynes
Diabetes is one of the largest health emergencies of the twenty-first century and it is increasing with alarming rate throughout the world. Glycemic Control in diabetes patients is an important issue in minimizing diabetes related complications and deaths. Institution based comparative cross-sectional study was conducted from March to April, 2017. Glycated Hemoglobin A1c and biochemical profiles were determined using Huma Meter A1c and ABX PENTRA 400 clinical chemistry analyzer. Independent t-test to compare groups, bivariate and multi variable logistic regression analysis were used...
May 18, 2018: Adipocyte
https://www.readbyqxmd.com/read/29774462/combining-gfr-estimates-from-cystatin-c-and-creatinine-what-is-the-optimal-mix
#3
Emil den Bakker, Reinoud Gemke, Joanna A E van Wijk, Isabelle Hubeek, Birgit Stoffel-Wagner, Arend Bökenkamp
BACKGROUND: Combining estimated glomerular filtration rate (eGFR) equations based on creatinine and cystatin C has been shown to improve the accuracy of GFR estimation. This study aims to optimize this strategy for height-independent GFR estimation in children. METHODS: Retrospective study of 408 inulin clearance tests with simultaneous International Federation of Clinical Chemistry-calibrated measurements of creatinine, cystatin C, and urea in children (mean age 12...
May 17, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29771317/exon-skipping-advances-for-duchenne-muscular-dystrophy
#4
Lucía Echevarría, Philippine Aupy, Aurélie Goyenvalle
Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle wasting that has currently no cure. Exon-skipping strategy represents one of the most promising therapeutic approaches that aims to restore expression of a shorter but functional dystrophin protein. The antisense field has remarkably progress over the last years with recent accelerated approval of the first ASO-based therapy for DMD, Exondys 51, though the therapeutic benefit remains to be proven in patients. Despite clinical advances, the poor effective delivery to target all muscle remains the main hurdle for antisense drug therapy...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29769005/adenosine-synthetic-methods-of-its-derivatives-and-antitumor-activity
#5
Margarita Gutierrez, Francisco Valdes, Victor Luna, Barbara Arevalo, Nelson Brown
Since 1929, several researchers have conducted studies in relation the nucleoside of adenosine (1) mainly distribution identifying, characterizing their biological importance and synthetic chemistry to which this type of molecule has been subjected to obtain multiple of its derivatives. The receptors that interact with adenosine and its derivatives, called purinergic receptors, are classified as A1, A2A, A2B and A3. In the presence of agonists and antagonists, these receptors are involved in various physiological processes and diseases...
May 16, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29768707/albumin-apheresis-for-artificial-liver-support-in-vitro-testing-of-a-novel-filter
#6
Tomasz Piatek, Joanna Giebultowicz, Marieke Rüth, Horst-Dieter Lemke, Florian Bonn, Piotr Wroczynski, Piotr Malkowski, Jacek Rozga
Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described...
May 16, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29768576/recent-advances-and-perspectives-in-cancer-drug-design
#7
Luma G Magalhaes, Leonardo L G Ferreira, Adriano D Andricopulo
Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments...
May 14, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29764242/morbidity-and-mortality-resulting-from-acute-inhalation-exposures-to-hydrogen-fluoride-and-carbonyl-fluoride-in-rats
#8
Adolph J Januszkiewicz, Matthew A Bazar, Lee C B Crouse, Michael A Chapman, Steven E Hodges, Steven J McCormick, Arthur J O'Neill
OBJECTIVE: Experiments were undertaken to compare morbidity and mortality from brief inhalation exposures to high levels of hydrogen fluoride (HF) and carbonyl fluoride (COF2 ). METHODS: Rats from both sexes were exposed for durations of 5 and 10 min to nominal concentrations of 10,000 to 57,000 ppm HF or 500 to 10,000 ppm COF2 . Respiration was monitored before, during, and after exposure. Animals were observed up to 6 days post-exposure. Terminal blood samples were collected for routine clinical chemistry and hematology...
May 15, 2018: Inhalation Toxicology
https://www.readbyqxmd.com/read/29763631/safety-evaluation-of-genetically-modified-das-40278-9-maize-in-a-subchronic-rodent-feeding-study
#9
Shiying Zou, Tianqi Lang, Xu Liu, Kunlun Huang, Xiaoyun He
Genetically modified (GM) maize, DAS-40278-9, expresses the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The aad-1 gene, which expresses the AAD-1 protein, was derived from Gram-negative soil bacterium, Sphingobium herbicidovorans. A 90-day sub-chronic toxicity study was conducted on rats as a component of the safety evaluation of DAS-40278-9 maize. Rats were given formulated diets containing maize grain from DAS-40278-9 or a non-GM near isogenic control comparator at an incorporation rate of 12...
May 12, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29760220/quantifying-atherogenic-lipoproteins-current-and-future-challenges-in-the-era-of-personalized-medicine-and-vldl-cholesterol-a-consensus-statement-from-eas-and-eflm
#10
Michel R Langlois, M John Chapman, Christa Cobbaert, Samia Mora, Alan T Remaley, Emilio Ros, Gerald F Watts, Jan Borén, Hannsjörg Baum, Eric Bruckert, Alberico Catapano, Olivier S Descamps, Arnold von Eckardstein, Pia R Kamstrup, Genovefa Kolovou, Florian Kronenberg, Anne Langsted, Kari Pulkki, Nader Rifai, Grazyna Sypniewska, Olov Wiklund, B Rge G Nordestgaard
BACKGROUND: The European Atherosclerosis Society-European Federation of Clinical Chemistry and Laboratory Medicine Consensus Panel aims to provide recommendations to optimize atherogenic lipoprotein quantification for cardiovascular risk management. CONTENT: We critically examined LDL cholesterol, non-HDL cholesterol, apolipoprotein B (apoB), and LDL particle number assays based on key criteria for medical application of biomarkers. ( a ) Analytical performance: Discordant LDL cholesterol quantification occurs when LDL cholesterol is measured or calculated with different assays, especially in patients with hypertriglyceridemia >175 mg/dL (2 mmol/L) and low LDL cholesterol concentrations <70 mg/dL (1...
May 14, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29757390/battery-longevity-of-implantable-cardioverter-defibrillators-and-cardiac-resynchronization-therapy-defibrillators-technical-clinical-and-economic-aspects-an-expert-review-paper-from-ehra
#11
Giuseppe Boriani, Josè Merino, David J Wright, Fredrik Gadler, Beat Schaer, Maurizio Landolina
In recent years an extension of devices longevity has been obtained for implantable cardioverter-defibrillators (ICDs), including ICDs for cardiac resynchronization therapy (CRT-D) through improved battery chemistry and device technology and this implies important clinical benefits (reduced need for device replacements and associated complications, particularly infections), as well as economic benefits, in line with patient preferences and needs. From a clinical point of view, the availability of this improvement in technology allows to better tune the choice of the device to be implanted, taking into account that the reasons supporting the value of an extended device longevity as a clinical priority may differ according to the clinical setting (purely electrical diseases or left ventricular dysfunction/heart failure, respectively)...
May 10, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29757133/haemolysis-index-for-the-screening-of-intravascular-haemolysis-a-novel-diagnostic-opportunity
#12
REVIEW
Giuseppe Lippi, Emmanuel J Favaloro, Massimo Franchini
The diagnostic approach to patients with intravascular haemolysis remains challenging, since no first-line laboratory test seems to be entirely suitable for the screening of this condition. Recent evidence shows that an enhanced cell-free haemoglobin (fHb) concentration in serum or plasma is a reliable marker of red blood cell injury, and may also predict clinical outcomes in patients with different forms of haemolytic anaemias. However, the routine use of the haemiglobincyanide assay, the current reference method for measuring fHb, seems unsuitable for a timely diagnosis of intravascular haemolysis, for many safety and practical reasons...
May 8, 2018: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/29756761/digital-microarrays-single-molecule-readout-with-interferometric-detection-of-plasmonic-nanorod-labels
#13
Derin Sevenler, George G Daaboul, Fulya Ekiz Kanik, Nese Lortlar Ünlü, M Selim Ünlu
DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and limited dynamic range of traditional fluorescence microarrays compared to other detection techniques have been the technology's Achilles' Heel, and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ('digital') regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages...
May 14, 2018: ACS Nano
https://www.readbyqxmd.com/read/29755770/safety-and-initial-efficacy-of-radiation-segmentectomy-for-the-treatment-of-hepatic-metastases%C3%A2
#14
Craig Meiers, Amy Taylor, Brian Geller, Beau Toskich
Background: Hepatic metastatectomy and ablation are associated with prolonged survival, but not all lesions are anatomically amenable to these therapies. We evaluated safety and initial efficacy of segmental ablative transarterial radioembolization, or radiation segmentectomy (RS), as a treatment for hepatic metastases. Methods: A single institution retrospective analysis was performed of patients with hepatic metastases, determined unamenable to resection by a multidisciplinary tumor board, treated with RS from 2015-2017...
April 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29755311/interactive-sonification-exploring-emergent-behavior-applying-models-for-biological-information-and-listening
#15
Insook Choi
Sonification is an open-ended design task to construct sound informing a listener of data. Understanding application context is critical for shaping design requirements for data translation into sound. Sonification requires methodology to maintain reproducibility when data sources exhibit non-linear properties of self-organization and emergent behavior. This research formalizes interactive sonification in an extensible model to support reproducibility when data exhibits emergent behavior. In the absence of sonification theory, extensibility demonstrates relevant methods across case studies...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29753163/baseline-renal-function-and-albumin-are-powerful-predictors-for-allogeneic-transplantation-related-mortality
#16
Roni Shouval, Cornelis N de Jong, Joshua Fein, Annoek E C Broers, Ivetta Danylesko, Avichai Shimoni, Marloes R Reurs, Adája E Baars, Niels van der Schaft, Arnon Nagler, Jan J Cornelissen
RATIONALE: Biomarkers measured in blood chemistry before allogeneic hematopoietic stem cell transplantation (HSCT) may reflect patients' physiological status. We hypothesized that selected markers are predictive for non-relapse mortality (NRM) following transplantation and could contribute to risk assessment. PATIENTS AND METHODS: We investigated the value of pre-HSCT albumin, estimated glomerular filtration rate (eGFR) and alkaline phosphatase (AlkP) in predicting NRM...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29746776/from-cancer-to-pain-target-by-automated-selectivity-inversion-of-a-clinical-candidate
#17
Samo Turk, Benjamin Merget, Sameh Eid, Simone Fulle
Elimination of inadvertent binding is crucial for inhibitor design targeting conserved protein classes like kinases. Compounds in clinical trials provide a rich source for initiating drug design efforts by exploiting such secondary binding events. Considering both aspects, we shifted the selectivity of tozasertib, originally developed against AurA as cancer target, towards the pain target TrkA. First, selectivity-determining features in binding pockets were identified by fusing interaction-grids of several key and off-target conformations...
May 10, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29746294/a-maintenance-three-day-per-week-schedule-with-the-single-tablet-regimen-efavirenz-emtricitabine-tenofovir-disoproxil-fumarate-is-effective-and-decreases-sub-clinical-toxicity-the-a-tri-week-pilot-trial
#18
Jhon Rojas, Jose L Blanco, Sonsoles Sanchez-Palomino, Maria A Marcos, Alberto C Guardo, Ana Gonzalez-Cordon, Montserrat Lonca, Amparo Tricas, Ana Rodriguez, Anabel Romero, Jose M Miro, Josep Mallolas, Jose M Gatell, Montserrat Plana, Esteban Martinez
BACKGROUND: Antiretroviral drugs contained in single tablet Atripla® have pharmacokinetic properties that could allow for longer than once-daily (OD) dosing. We hypothesized that simplifying Atripla® OD to 3-day per week would be feasible, able to maintain viral suppression and less toxic. METHODS: Virologically suppressed (≥2 years) HIV+ adults on Atripla® OD, CD4 >350/mm at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their OD regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W)...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29745657/what-makes-a-great-medicinal-chemist-a-personal-perspective
#19
Mark A Murcko
Although it is extremely challenging to invent new medicines, I have observed that certain behaviors seem to be commonly found among successful medicinal chemists. Those who exhibit most of these character traits are far more likely to bring new drugs into the clinic and onto the market. And, importantly, organizations that encourage these behaviors are far more likely to be successful. These traits can be broken into two categories: "general" and "discipline-specific." General traits are those that are common to all great scientists, while the discipline-specific ones are more specialized behaviors relevant to the medicinal chemistry enterprise...
May 10, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29741201/effects-of-fermented-papaya-preparation-fpp-on-safety-outcomes-in-older-adults-a-short-report-of-a-placebo-controlled-clinical-trial
#20
R T Mankowski, C Leeuwenburgh, T M Manini, A J Woods, S D Anton
Fermented Papaya Preparation (FPP®) has shown antioxidative and anti-inflammatory effects in preclinical and clinical aging studies. However, clinical trials are needed to fully evaluate the safety of FPP® in moderate-functioning, generally healthy older adults. In this randomized (9g/day of FPP® or placebo), crossover design study, we enrolled 30 older moderate-functioning older adults (70-100 years old). The participants completed both a treatment and a placebo condition. After eight (8) weeks on each of these regimens (with a 4-week wash-out period in between), participants had their venous blood drawn for assessment of blood chemistries, metabolic outcomes and inflammatory biomarkers...
2018: Journal of Frailty & Aging
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