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Clinical chemistry

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https://www.readbyqxmd.com/read/29342358/synthesis-and-biological-characterization-of-aryl-uracil-inhibitors-of-hepatitis-c-virus-ns5b-polymerase-discovery-of-abt-072-a-trans-stilbene-analog-with-good-oral-bioavailability
#1
John Randolph, A Chris Krueger, Pamela Donner, John K Pratt, Dachun Liu, Christopher E Motter, Todd W Rockway, Mike D Tufano, Rolf Wagner, Hock B Lim, Jill M Beyer, Rubina Mondal, Neeta S Panchal, Lynn Colletti, Yaya Liu, Gennadiy Koev, Warren M Kati, Lisa E Hernandez, David W A Beno, Kenton L Longenecker, Kent D Stewart, Emily O Dumas, Akhteruzzaman Molla, Clarence Maring
ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection. This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication. Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility, and provided much better pharmacokinetic properties in preclinical species...
January 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29341965/osmotic-shifts-cerebral-edema-and-neurologic-deterioration-in-severe-hepatic-encephalopathy
#2
Eric Michael Liotta, Anna L Romanova, Bryan D Lizza, Laura J Rasmussen-Torvik, Minjee Kim, Brandon Francis, Rajbeer Singh Sangha, Timothy J Carroll, Daniel Ganger, Daniela P Ladner, Andrew M Naidech, James J Paparello, Shyam Prabhakaran, Farzaneh A Sorond, Matthew B Maas
OBJECTIVES: We sought to determine the effect of acute electrolyte and osmolar shifts on brain volume and neurologic function in patients with liver failure and severe hepatic encephalopathy. DESIGN: Retrospective analysis of brain CT scans and clinical data. SETTING: Tertiary care hospital ICUs. PATIENTS: Patients with acute or acute-on-chronic liver failure and severe hepatic encephalopathy. INTERVENTIONS: Clinically indicated CT scans and serum laboratory studies...
February 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29341939/the-quest-for-equivalence-of-test-results-the-pilgrimage-of-the-dutch-calibration-2-000-program-for-metrological-traceability
#3
REVIEW
Rob T P Jansen, Christa M Cobbaert, Cas Weykamp, Marc Thelen
Calibration 2.000 was initiated 20 years ago for standardization and harmonization of medical tests. The program also intended to evaluate adequate implementation of the In Vitro Diagnostics (IVD) 98/79/EC directive, in order to ensure that medical tests are fit-for-clinical purpose. The Calibration 2.000 initiative led to ongoing verification of test standardization and harmonization in the Netherlands using commutable external quality assessment (EQA)-tools and a type 1 EQA-design, where feasible. National support was guaranteed by involving all laboratory professionals as well as laboratory technicians responsible for EQA and quality officers...
January 17, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29340006/the-impact-of-the-progressive-efficiency-test-on-a-rowing-ergometer-on-white-blood-cells-distribution-and-clinical-chemistry-changes-in-paralympic-rowers-during-the-preparatory-stage-before-the-paralympic-games-in-rio-2016-a-case-report
#4
Robert Nowak, Rafał Buryta, Krzysztof Krupecki, Tomasz Zając, Marek Zawartka, Patrizia Proia, Dorota Kostrzewa-Nowak
There is a large gap in knowledge regarding research on post-exercise blood changes in disabled athletes. There are relatively few data on adaptive mechanisms to exercise in disabled athletes, including disabled rowers. Two rowers from a Polish adaptive rowing settle TAMix2x that qualified for the Paralympic Games in Rio, 2016 took part in this study. They performed a progressive test on a rowing ergometer until exhaustion. The cardiorespiratory fitness measures, complete blood count, white blood cells' distribution and 30 clinical chemistry variables describing laboratory diagnostic profiles and general health were determined...
December 2017: Journal of Human Kinetics
https://www.readbyqxmd.com/read/29339355/re-evaluation-of-the-normal-range-of-serum-total-co2-concentration
#5
REVIEW
Jeffrey A Kraut, Nicolaos E Madias
A reliable determination of blood pH, PCO2, and [HCO3-] is necessary for assessing the acid-base status of a patient. However, most acid-base disorders are first recognized through abnormalities in serum total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3-]. In screening patients on the basis of serum [TCO2], we have been concerned about the wide limits of normal for serum [TCO2], 10-13 mEq/L, reported by many clinical laboratories. Indeed, we have encountered patients with serum [TCO2] values within the lower or upper end of the normal range of the reporting laboratory, who subsequently were shown to have a cardinal acid-base disorder...
January 16, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29334816/anti-colchicine-fab-fragments-prevent-lethal-colchicine-toxicity-in-a-porcine-model-a-pharmacokinetic-and-clinical-study
#6
Michael Eddleston, Nicolas Fabresse, Adrian Thompson, Ibrahim Al Abdulla, Rachael Gregson, Tim King, Alain Astier, Frederic J Baud, R Eddie Clutton, Jean-Claude Alvarez
BACKGROUND: Colchicine poisoning is commonly lethal. Colchicine-specific Fab fragments increase rat urinary colchicine clearance and have been associated with a good outcome in one patient. We aimed to develop a porcine model of colchicine toxicity to study the pharmacokinetics and efficacy of ovine Fab. METHODS: A Göttingen minipig critical care model was established and serial blood samples taken for colchicine and Fab pharmacokinetics, clinical chemistry, and haematology...
January 15, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29334758/anticancer-thiosemicarbazones-chemical-properties-interaction-with-iron-metabolism-and-resistance-development
#7
Petra Heffeter, Veronika F S Pape, Eva A Enyedy, Bernhard K Keppler, Gergely Szakas, Christian R Kowol
SIGNIFICANCE: During the last decades, thiosemicarbazones have been clinically developed for a variety of diseases including tuberculosis, viral infections, malaria and cancer. With regard to malignant diseases, the class of α-N-heterocyclic thiosemicarbazones, and here especially Triapine, was intensively developed in multiple clinical phase I/II trials. Recent Advances: Very recently two new derivatives, namely COTI-2 and DpC have entered phase I evaluation. Based on the strong metal-chelating/metal-interacting properties of thiosemicarbazones, interference with the cellular iron (and copper) homeostasis is assumed to play an important role in their biological activity...
January 15, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29333106/which-point-of-care-tests-would-be-most-beneficial-to-add-to-clinical-practice-findings-from-a-survey-of-3-family-medicine-clinics-in-the-united-states
#8
Victoria Hardy, William Alto, Gina A Keppel, Laura-Mae Baldwin, Matthew Thompson
Background: Point-of-care tests (POCTs) are increasingly used in family medicine to facilitate screening, diagnosis, monitoring, treatment, and referral decisions for a variety of conditions. Point-of-care tests that clinicians believe might be beneficial to add to clinical practice and the conditions for which they would be most useful in family medicine remain poorly understood in the United States. Methods: Forty-two clinicians at 3 family medicine residency clinics completed a brief survey asking which POCTs they believed would be beneficial to add to their clinical practice and the conditions POCTs would be most useful for...
December 2017: Point of Care
https://www.readbyqxmd.com/read/29330255/high-intensity-cigarette-smoking-is-associated-with-incident-diabetes-mellitus-in-black-adults-the-jackson-heart-study
#9
Wendy B White, Loretta R Cain, Emelia J Benjamin, Andrew P DeFilippis, Michael J Blaha, Wei Wang, Victoria Okhomina, Rachel J Keith, Mahmoud Al Rifai, Sina Kianoush, Michael D Winniford, Rose M Robertson, Aruni Bhatnagar, Adolfo Correa, Michael E Hall
BACKGROUND: Previous reports on whether smoking is associated with insulin resistance and diabetes mellitus have yielded inconsistent findings. We aimed to evaluate the relationship between cigarette smoking and incident diabetes mellitus in the Jackson Heart Study. METHODS AND RESULTS: Jackson Heart Study participants enrolled at baseline without prevalent diabetes mellitus (n=2991) were classified by self-report as current smokers, past smokers (smoked ≥400 cigarettes/life and no longer smoking), or never smokers...
January 12, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29327219/pharmacological-insights-into-the-use-of-apomorphine-in-parkinson-s-disease-clinical-relevance
#10
REVIEW
Manon Auffret, Sophie Drapier, Marc Vérin
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic...
January 11, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29326420/fasting-and-glucose-induced-thermogenesis-in-response-to-three-ambient-temperatures-a-randomized-crossover-trial-in-the-metabolic-syndrome
#11
K Pathak, R J Woodman, A P James, M J Soares
BACKGROUND/OBJECTIVES: Cold exposure increases thermogenesis and could improve insulin sensitivity. We hypothesized a blunted response in the metabolic syndrome (MetS). SUBJECTS/METHODS: Twenty older adults 59 ± 10.4 years (with MetS, MetS+, n = 9; without MetS, MetS-, n = 11) completed a randomized crossover design of 3.5 h exposures to 20, 25 and 27 °C on three visits. After an hour's rest at the desired temperature, resting metabolic rate (RMR), respiratory quotient (RQ), forearm to fingertip gradients (FFG), and in the ear temperature (IET) were measured over 30 min...
January 11, 2018: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29324792/critical-evaluation-of-colon-submucosal-microdialysis-in-awake-mobile-rats
#12
Norbert Cibicek, Jiri Ehrmann, Jitka Proskova, Rostislav Vecera
Sensors able to record large bowel physiology and biochemistry in situ in awake rodents are lacking. Microdialysis is a mini-invasive technique that may be utilized to continuously deliver or recover low-molecular substances from various tissues. In this experiment we evaluated the feasibility of in vivo microdialysis to monitor extracellular fluid chemistry in the descending colon submucosa of conscious, freely moving rodents. Following surgical implantation of a microdialysis probe, male Wistar rats were housed in metabolic cages where they were analgized and clinically followed for four days with free access to standard diet and water...
2018: PloS One
https://www.readbyqxmd.com/read/29324340/antimalarial-naphthoquinones-synthesis-via-click-chemistry-in%C3%A2-vitro-activity-docking-to-pfdhodh-and-sar-of-lapachol-based-compounds
#13
Geraldo Célio Brandão, Franciele C Rocha Missias, Lucas Miquéias Arantes, Luciana Ferreira Soares, Kuldeep K Roy, Robert J Doerksen, Alaide Braga de Oliveira, Guilherme Rocha Pereira
Lapachol is an abundant prenyl naphthoquinone occurring in Brazilian Bignoniaceae that was clinically used, in former times, as an antimalarial drug, despite its moderate effect. Aiming to search for potentially better antimalarials, a series of 1,2,3-triazole derivatives was synthesized by chemical modification of lapachol. Alkylation of the hydroxyl group gave its propargyl ether which, via copper-catalyzed cycloaddition (CuAAC) click chemistry with different organic azides, afforded 17 naphthoquinonolyl triazole derivatives...
December 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29324183/technologies-for-measuring-pharmacokinetic-profiles
#14
A A Heller, S Y Lockwood, T M Janes, D M Spence
The creation of a pharmacokinetic (PK) curve, which follows the plasma concentration of an administered drug as a function of time, is a critical aspect of the drug development process and includes such information as the drug's bioavailability, clearance, and elimination half-life. Prior to a drug of interest gaining clearance for use in human clinical trials, research is performed during the preclinical stages to establish drug safety and dosing metrics from data obtained from the PK studies. Both in vivo animal models and in vitro platforms have limitations in predicting human reaction to a drug due to differences in species and associated simplifications, respectively...
January 11, 2018: Annual Review of Analytical Chemistry
https://www.readbyqxmd.com/read/29323467/interactions-between-clinically-used-bisphosphonates-and-bone-mineral-from-coordination-chemistry-to-biomedical-applications-and-beyond
#15
Joanna Gałęzowska
Bisphosphonates (BPs) are well established, widely used first-choice drugs for bone-related diseases and are one of the few classes of molecules for selective bone-targeting. Their binding to calcium cations within hydroxyapatite (HA) is a key physico-chemical event taking place on the bone surface. It is the starting point for a cascade of biochemical reactions and cellular effects that lead to the pharmacological activity of BPs. The phenomenon is known for years, yet still its physicochemical nature is not fully understood...
January 11, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29322647/max-bergmann-award-lecture-macromolecular-medicinal-chemistry-as-applied-to-metabolic-diseases
#16
REVIEW
Richard D DiMarchi, John P Mayer, Vasily M Gelfanov, Matthias Tschöp
This review presents the scope of research presented in an October 2016 lecture pertaining to the award of the 2015 Max Bergmann Medal. The advancement in synthetic and biosynthetic chemistry as applied to the discovery of novel macromolecular drug candidates is reviewed. The evolution of the technology from the design, synthesis, and development of the first biosynthetic peptides through the emergence of peptide-based incretin agonists that function by multiple biological mechanisms is exemplified by the progression of such peptides from preclinical to clinical study...
January 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29319937/medical-devices-clinical-chemistry-and-clinical-toxicology-devices-classification-of-the-reagents-for-molecular-diagnostic-instrument-test-systems-final-order
#17
(no author information available yet)
The Food and Drug Administration (FDA or we) is classifying the reagents for molecular diagnostic instrument test systems into class I (general controls). We are taking this action because we have determined that classifying the device into class I (general controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.
December 27, 2017: Federal Register
https://www.readbyqxmd.com/read/29316363/exploiting-advanced-hydrogel-technologies-to-address-key-challenges-in-regenerative-medicine
#18
REVIEW
Daniel A Foyt, Michael D A Norman, Tracy T L Yu, Eileen Gentleman
Regenerative medicine aims to tackle a panoply of challenges from repairing focal damage to articular cartilage to preventing pathological tissue remodeling after myocardial infarction. Hydrogels are water-swollen networks formed from synthetic or naturally derived polymers and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues' dynamic and nonlinear physical properties...
January 9, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29315702/strategies-to-target-the-hedgehog-signaling-pathway-for-cancer-therapy
#19
REVIEW
Minhang Xin, Xinyue Ji, Ladie Kimberly De La Cruz, Suresh Thareja, Binghe Wang
Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29315675/chemical-modifications-of-nucleic-acid-drugs-and-their-delivery-systems-for-gene-based-therapy
#20
REVIEW
Changmai Chen, Zhenjun Yang, Xinjing Tang
Gene-based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene-based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs...
January 5, 2018: Medicinal Research Reviews
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