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Richard D Carvajal, Sophie Piperno-Neumann, Ellen Kapiteijn, Paul B Chapman, Stephen Frank, Anthony M Joshua, Josep M Piulats, Pascal Wolter, Veronique Cocquyt, Bartosz Chmielowski, T R Jeffry Evans, Lauris Gastaud, Gerald Linette, Carola Berking, Jacob Schachter, Manuel J Rodrigues, Alexander N Shoushtari, Delyth Clemett, Dana Ghiorghiu, Gabriella Mariani, Shirley Spratt, Susan Lovick, Peter Barker, Elaine Kilgour, Zhongwu Lai, Gary K Schwartz, Paul Nathan
Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial...
March 12, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Soumya Moonjely, Nemat O Keyhani, Michael J Bidochka
The hyd1/hyd2 hydrophobins are important constituents of the conidial cell wall of the insect pathogenic fungus Beauveria bassiana. This fungus can also form intimate associations with several plant species. Here, we show that inactivation of two Class I hydrophobin genes, hyd1 or hyd2, significantly decreases the interaction of B. bassiana with bean roots. Curiously, the ∆hyd1/∆hyd2 double mutant was less impaired in root association than Δhyd1 or Δhyd2. Loss of hyd genes affected growth rate, conidiation ability and oosporein production...
March 8, 2018: Microbiology
Jianhong Liao, Haoran Zheng, Zengming Fei, Bo Lu, Hua Zheng, Dan Li, Xiong Xiong, Ying Yi
In this study, intracellular pH-responsive nanoparticles (NPs) of hyaluronic acid-hydrazone linkage-doxorubicin (HA-hyd-DOX) were designed and prepared for acid-triggered release of doxorubicin through a hydrazone linkage. A series of amphiphilic polymeric prodrugs were obtained, which can be self-assembled in aqueous media, the formed NPs exhibited a spherical core-shell type and the uniform size was ranging from 167 to 220 nm. Moreover, the HA-hyd-DOX NPs exhibited a good stability in vitro and the drug release profiles showed that the DOX release was obviously mediated by pH gradient...
March 2, 2018: International Journal of Biological Macromolecules
Battini Swapna, M K Chaitanya Mannava, Ashwini Nangia
The classic FDC of four TB drugs, namely Rifampicin (RIF), Isoniazid (INH), Pyrazinamide (PZA) and Ethambutol Dihydrochloride (EDH) has the twin issues of physical stability and rifampicin cross-reaction in the 4FDC. The major reason for these quality issues is the interaction between RIF and INH to yield isonicotinyl hydrazone (HYD) in drug tablets. Pharmaceutical cocrystals of INH with caffeic acid (PZA + EDH + RIF + INH-CFA cocrystal) and vanillic acid (PZA + EDH + RIF + INH-VLA cocrystal) are able to stabilize the FDC formulation compared to the reference batch (PZA + EDH + RIF + INH)...
February 17, 2018: Journal of Pharmaceutical Sciences
Marianne Knuth, Oliver Temme, Thomas Daldrup, Evelyn Pawlik
For different reasons, street cocaine is often diluted with pharmacologically active substances, the so-called adulterants such as levamisole or hydroxyzine. A controversial debate exists currently on the uptake of adulterants from cocaine preparations and drug-related death. Previous research convincingly argues that serious adverse side effects that affect the central nervous and cardiovascular systems can be a consequence of adulterated cocaine. AIMS: Having identified the presence of adulterants in lung tissue and blood, the concentrations of these substances in brain, an important target location, was of interest...
February 10, 2018: Forensic Science International
L Mountrakis, E Lorenz, A G Hoekstra
The immersed-boundary lattice-Boltzmann method (IB-LBM) is increasingly being used in simulations of dense suspensions. These systems are computationally very expensive and can strongly benefit from lower resolutions that still maintain the desired accuracy for the quantities of interest. IB-LBM has a number of free parameters that have to be defined, often without exact knowledge of the tradeoffs, since their behavior in low resolutions is not well understood. Such parameters are the lattice constant Δx, the number of vertices N_{v}, the interpolation kernel ϕ, and the LBM relaxation time τ...
July 2017: Physical Review. E
Mojtaba Shamsipur, Mahdi Emami, Leila Farzin, Reza Saber
The sensitive quantification of Human Epidermal growth factor Receptor 2 (HER2), as a key prognostic tumor marker, plays a critical role in screening, early diagnosis and management of breast cancer. This paper describes a sandwich-type immunoassay with silver signal enhancement strategy for highly sensitive detection of HER2. For this purpose, the target capturing step was designed by functionalization of 3-aminopropyltrimethoxysilane coated magnetite nanoparticles with antibody (antiHER2/APTMS-Fe3O4), as a platform bioconjugate (PB), and immobilized at a bare GCE...
December 20, 2017: Biosensors & Bioelectronics
J M Green, Miller Bl, J D Simpson, Dubroc Dr, Keyes Aa, Neal Kk, Gann Jj, Andre Tl
The lactate [La] threshold can predict endurance performance potential. Dehydration may alter [La] threshold. This study examined effects of dehydration on [La] response during constant load cycling. Recreationally fit (VO2 peak = 48.7 ± 5.2 ml•kg•min) male participants (n=9) completed 2 x 40 min constant-load cycling trials; euhydrated (HYD) and following previous evening passive (water bath) dehydration (2% body weight, DEH) (HYD and DEH counterbalanced). [La], heart rate (HR), 10 point Omni Ratings of Perceived Exertion (RPE) and rectal temperature (Trec) were measured following warm-up and at 10, 20, 30, and 40 min...
December 11, 2017: Journal of Strength and Conditioning Research
Haiyang Zhang, Yang Jiang, Hai Yan, Ziheng Cui, Chunhua Yin
Experimental observations for ionic hydration free energies are highly debated mainly due to the ambiguous absolute hydration free energy of proton, ΔGhyd * (H+ ). Hydration free energies (HFEs) of the 112 singly charged ions in the Minnesota solvation database were predicted by six methods with explicit and implicit solvent models, namely, thermodynamic integration (TI), energy representation module (ERmod), three-dimensional reference interaction site model (3D-RISM), and continuum solvation models based on the quantum mechanical charge density (SMD) and on the Poisson-Boltzmann (PB) and generalized Born (GB) theories...
November 27, 2017: Journal of Chemical Information and Modeling
Raghu Ramanathan, Karthikeyan Sivanesan
The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites...
January 1, 2017: Journal of Pharmacy Practice
Mary Bond, Kerri A Schoedel, Laura Rabinovich-Guilatt, Maciej Gasior, William Tracewell, Richard Malamut, Yuju Ma, Lynn R Webster
Objective: To assess the intranasal abuse potential of hydrocodone extended-release (ER) tablets developed with CIMA Abuse-Deterrence Technology compared with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER, original formulation [HYD-OF]). Design: Single-dose, randomized, double-blind, quadruple-dummy, active- and placebo-controlled, crossover study. Setting: One US site. Subjects: Healthy, adult, nondependent, recreational opioid users...
June 14, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
S J Hartman, O N Genther-Schroeder, S L Hansen
A 2 × 2 factorial assessed the effect of trace mineral (TM) sources fed within low- or high-S diets on the mineral status and performance of cattle. Angus crossbred steers ( = 48; 6/pen) were blocked by BW (316 ± 16.6 kg), assigned to low-S (0.27%; LS) or high-S (0.54%; HS; added as CaSO) diets, and supplemented TM at 10 mg Cu, 30 mg Zn, and 20 mg Mn/kg DM from hydroxy (HYD; IntelliBond; Micronutrients USA LLC, Indianapolis, IN) or inorganic (sulfates; ING) sources ( = 12 steers/treatment). Steers were fed corn silage and corn-based diets via GrowSafe bunks in the growing period (GP; 84 d) and finishing period (FP; 77 d), respectively...
September 2017: Journal of Animal Science
S J Hartman, O N Genther-Schroeder, S L Hansen
A 2 × 2 factorial assessed the effect of trace mineral (TM) sources fed within low- or high-S diets on the mineral status and performance of cattle. Angus crossbred steers ( = 48; 6/pen) were blocked by BW (316 ± 16.6 kg), assigned to low-S (0.27%; LS) or high-S (0.54%; HS; added as CaSO) diets, and supplemented TM at 10 mg Cu, 30 mg Zn, and 20 mg Mn/kg DM from hydroxy (HYD; IntelliBond; Micronutrients USA LLC, Indianapolis, IN) or inorganic (sulfates; ING) sources ( = 12 steers/treatment). Steers were fed corn silage and corn-based diets via GrowSafe bunks in the growing period (GP; 84 d) and finishing period (FP; 77 d), respectively...
September 2017: Journal of Animal Science
M C Martínez-Herrero, M M Garijo-Toledo, D Liebhart, P Ganas, R A Martínez-Díaz, F Ponce-Gordo, A Carrero-Ruiz, M Hess, M T Gómez-Muñoz
Extensive diversity has been described within the avian oropharyngeal trichomonad complex in recent years. In this study we developed clonal cultures from four isolates selected by their different ITS1/5.8S/ITS2 (ITS) genotype and their association with gross lesions of avian trichomonosis. Isolates were obtained from an adult racing pigeon and a nestling of Eurasian eagle owl with macroscopic lesions, and from a juvenile wood pigeon and an European turtle dove without clinical signs. Multi-locus sequence typing analysis of the ITS, small subunit of ribosomal rRNA (SSUrRNA) and Fe-hydrogenase (Fe-hyd) genes together with a morphological study by optical and scanning electron microscopy was performed...
August 31, 2017: Infection, Genetics and Evolution
Louise Taber, T Christopher Bond, Xuezhe Wang, Aditi Kadakia, Tracy J Mayne
BACKGROUND AND OBJECTIVE: Hydrocodone bitartrate extended release (Hysingla(®) ER, HYD) was previously studied in a 12-week randomized, double-blind, placebo-controlled trial and a 52-week open-label safety study. Both of these preapproval studies allowed dose titration to efficacy. The purpose of the present analysis was to compare dosing and utilization patterns in these previous clinical trials with real-world data (RWD) usage in a retrospective claim analysis performed 12-14 months post approval in the US...
2017: Journal of Pain Research
Louise Taber, Ellie He, Steven R Ripa
AIM: Long-term safety and effectiveness of a once daily, single-entity, extended-release formulation of hydrocodone bitartrate (HYD) for the treatment of moderate to severe noncancer and nonneuropathic pain among patients with and without concurrent depression/anxiety at baseline. MATERIALS & METHODS: Post hoc analysis. RESULTS: HYD demonstrated a safety profile consistent with μ-opioid agonists: Serious adverse events in 12% patients with depression/anxiety including four deaths; 6% without depression/anxiety including one death...
July 27, 2017: Pain Management
G L Sa, X P Xiong, J G Ren, J Y Wang, H F Xia, Z K Liu, S G He, Y F Zhao
Oral epithelial adhesion to the lamina propria underlies the physiologic function of the oral mucosa and contributes to resisting bacterial invasion, preventing body fluid loss, and maintaining routine chewing; thus, understanding the factors that positively influence oral epithelial adhesion is a research topic of great interest. Rete pegs contribute to oral epithelial adhesion by enlarging the contact areas, whereas integrins are the major molecules that mediate epithelial cell adhesion to the basement membrane...
December 2017: Journal of Dental Research
Ute Lindenstrauß, Philipp Skorupa, Jennifer S McDowall, Frank Sargent, Constanze Pinske
The assembly of multi-protein complexes requires the concerted synthesis and maturation of its components and subsequently their co-ordinated interaction. The membrane-bound formate hydrogenlyase (FHL) complex is the primary hydrogen-producing enzyme in Escherichia coli and is composed of seven subunits mostly encoded within the hycA-I operon for [NiFe]-hydrogenase-3 (Hyd-3). The HycH protein is predicted to have an accessory function and is not part of the final structural FHL complex. In this work, a mutant strain devoid of HycH was characterised and found to have significantly reduced FHL activity due to the instability of the electron transfer subunits...
August 11, 2017: Biochemical Journal
Linlin Xiu, Gansheng Zhong, Dianna Liu, Shaohong Chen, Haiyan Liu, Feng Chen
BACKGROUND: Haizao Yuhu Decoction has been widely used to treat thyroid-related diseases especially goiter with few side effects in traditional Chinese medicine (TCM), including herb pair Sargassum (HZ) and Glycyrrhizae Radix et Rhizoma (GC), as one of "eighteen antagonistic medicaments." The two different species of Sargassum, Sargassum fusiforme (Sf) and Sargassum pallidum (Sp), are not clearly differentiated in clinical use, so that herb pair Sf-GC and Sp-GC could show different effect and toxicity...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Elizabeth Ofili, Inder Anand, Richard Allen Williams, Ola Akinboboye, Liou Xu, Gary Puckrein
INTRODUCTION: Based upon the findings of the African-American Heart Failure Trial, the US Food and Drug Administration approved the fixed-dose combination of isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HYD) (FDC-ISDN/HYD) as a new drug for treatment of heart failure (HF) in self-identified African Americans. According to the FDA, FDC-ISDN/HYD has no therapeutic equivalent. However, off-label combinations of the separate generic drugs ISDN and HYD (OLC-ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are routinely substituted without any supporting outcome data...
August 2017: Advances in Therapy
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