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https://www.readbyqxmd.com/read/28944986/development-and-in-vitro-in-vivo-evaluation-of-a-novel-benznidazole-liquid-dosage-form-using-a-quality-by-design-approach
#1
Higo Fernando Santos Souza, Daniel Real, Darío Leonardi, Sandra Carla Rocha, Victoria Alonso, Esteban Serra, Ariel Mariano Silber, Claudio Javier Salomon
OBJECTIVES: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. METHODS: In a quality-by-design approach a systematic optimization procedure was carried out in order to estimate the values of the factors leading to the maximum drug concentration. The formulations were analyzed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in-vivo palatability assay...
September 25, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28944759/optimization-of-an-ultralow-dose-high-resolution-pediatric-pet-scanner-design-based-on-monolithic-scintillators-with-dual-sided-digital-sipm-readout-a-simulation-study
#2
Ekaterina Mikhaylova, Valerio Tabacchini, Giacomo Borghi, Pieter Mollet, Ester D'Hoe, Dennis R Schaart, Stefaan Vandenberghe
The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32 × 32 mm<sup>2</sup> monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier (dSiPM) arrays. The six considered designs differ in axial lengths (27...
September 25, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28944229/targeting-trisomic-treatments-optimizing-dyrk1a-inhibition-to-improve-down-syndrome-deficits
#3
REVIEW
Megan Stringer, Charles R Goodlett, Randall J Roper
Overexpression of Dual-specificity tyrosine-phosphorylated regulated kinase 1A (DYRK1A), located on human chromosome 21, may alter molecular processes linked to developmental deficits in Down syndrome (DS). Trisomic DYRK1A is a rational therapeutic target, and although reductions in Dyrk1a genetic dosage have shown improvements in trisomic mouse models, attempts to reduce Dyrk1a activity by pharmacological mechanisms and correct these DS-associated phenotypes have been largely unsuccessful. Epigallocatechin-3-gallate (EGCG) inhibits DYRK1A activity in vitro and this action has been postulated to account for improvement of some DS-associated phenotypes that have been reported in preclinical studies and clinical trials...
September 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28943993/effectiveness-of-a-glycylcycline-antibiotic-for-reducing-the-pathogenicity-of-superantigen-producing-methicillin-resistant-staphylococcus-aureus-in-burn-wounds
#4
Lauren B Nosanov, Daniel Y Jo, Pranay R Randad, Lauren T Moffatt, Bonnie C Carney, Rachel T Ortiz, Jeffrey W Shupp
Objective: Burn-injured patients are highly susceptible to infectious complications, which are often associated with increased morbidity and mortality. Rates of antibiotic resistance have increased, and resistant species such as methicillin-resistant Staphylococcus aureus provide additional challenges in the form of virulence factors. Proteins can disrupt local healing, leading to systemic immune disruption. To optimize outcomes, treatments that reduce pathogenicity must be identified. This study aims to compare a glycylcycline antibiotic-tigecycline-with clindamycin for effectiveness in treating superantigenic methicillin-resistant Staphylococcus aureus in burn wounds...
2017: Eplasty
https://www.readbyqxmd.com/read/28943823/population-pharmacokinetics-and-pharmacodynamic-target-attainment-of-meropenem-in-critically-ill-young-children
#5
Jeffrey J Cies, Wayne S Moore, Adela Enache, Arun Chopra
OBJECTIVE: This study aims to describe the population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically ill children. METHODS: The study involved a retrospective medical record review from a 189-bed, freestanding children's tertiary care teaching hospital of patients ages 1 to 9 years who received meropenem with concurrent therapeutic drug monitoring. RESULTS: There were 9 patients ages 1 to 9 years (mean age, 3...
July 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28943819/evaluation-of-safety-in-exceeding-maximum-adult-doses-of-commonly-used-second-generation-antiepileptic-drugs-in-pediatric-patients
#6
Mindl M Messinger, Sunita N Misra, Gary D Clark, Shannon M DiCarlo
OBJECTIVE: Pediatric patients often require larger doses of antiepileptic drug (AED) than adults in order to attain therapeutic serum concentrations and/or achieve seizure control. Safety and efficacy data are often extrapolated from adult literature; hence, optimal dosage may only be determined anecdotally or based on expert opinion. With limited pediatric dosing guidelines, milligrams per day that are based on weight may exceed the maximum adult dose. The primary objective of this study is to evaluate the safety of exceeding maximum doses as specified by the US Food and Drug Administration or manufacturers of commonly used AEDs in pediatric patients...
July 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28943204/considerations-for-antibiotic-prophylaxis-in-head-and-neck-cancer-surgery
#7
Michael P Veve, Susan L Davis, Amy M Williams, John E McKinnon, Tamer A Ghanem
Peri/post-operative antibiotic prophylaxis (POABP) has become standard practice for preventing surgical site infections (SSI) in head and neck cancer patients undergoing microvascular reconstruction, but few data exist on optimal POABP regimens. Current surgical prophylaxis guideline recommendations fail to account for the complexity of microvascular reconstruction relative to other head and neck procedures, specifically regarding wound classification and antibiotic duration. Selection of POABP spectrum is also controversial, and must balance the choice between too narrow, risking subsequent infection, or too broad, and possible unwanted effects (e...
September 21, 2017: Oral Oncology
https://www.readbyqxmd.com/read/28943074/local-protocol-variations-for-image-guided-radiation-therapy-in-the-multicenter-dutch-hypofractionation-hypro-trial-impact-of-rectal-balloon-and-mri-delineation-on-anorectal-dose-and-gastrointestinal-toxicity-levels
#8
R C Wortel, W D Heemsbergen, R J Smeenk, M G Witte, A D Krol, F J Pos, L Incrocci
PURPOSE: The phase 3 HYpofractionated irradiation for PROstate cancer (HYPRO) trial randomized patients with intermediate- to high-risk localized prostate cancer to conventionally fractionated (78 Gy in 39 fractions) or hypofractionated (64.6 Gy in 19 fractions) radiation therapy. Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers...
August 3, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28943045/prognostic-factors-for-tube-feeding-dependence-after-curative-chemo-radiation-in-head-and-neck-cancer-a-systematic-review-of-literature
#9
REVIEW
Kim Wopken, Hendrik P Bijl, Johannes A Langendijk
BACKGROUND: Tube feeding dependence is a commonly observed debilitating side-effect of curative (chemo-) radiation in head and neck cancer patients that severely affects quality of life. Prevention of this side-effect can be obtained using advanced radiation techniques, such as IMRT. For radiotherapy treatment plan optimization, it has become increasingly important to develop prediction models that enable clinicians to predict the risk of tube feeding dependence for individual patients...
September 21, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28942680/brain-targeted-oral-delivery-of-doxycycline-hydrochloride-encapsulated-tween-80-coated-chitosan-nanoparticles-against-ketamine-induced-psychosis-behavioral-biochemical-neurochemical-and-histological-alterations-in-mice
#10
Monu Yadav, Milind Parle, Nidhi Sharma, Sameer Dhingra, Neha Raina, Deepak Kumar Jindal
To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3(2) full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28942257/optimization-of-the-precursor-removal-of-dichloroacetonitrile-dcan-an-emerging-nitrogenous-disinfection-by-product-in-an-up-flow-bac-filter
#11
Shuai Wang, Tao Lin, Wei Chen, Han Chen
The process parameters of the up-flow biological activated carbon filter (UBACF) were optimized in a pilot-scale trial for controlling the precursor of dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product. The experiments were performed using a central composite design (CCD) with the response surface methodology (RSM). The results showed that the removal efficiencies of formation potentials (FP) of DCAN increased from 28.9% to 64.4% with the optimized ozone dose, expansion rate of BAC and backwashing cycle, being scheduled to 1...
September 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28942018/integration-of-fmri-and-meg-functional-maps-into-a-cyberknife-planning-system-feasibility-study-for-motor-activity-localization-and-dose-planning
#12
Elena De Martin, Dunja Duran, Francesco Ghielmetti, Elisa Visani, Domenico Aquino, Marcello Marchetti, Davide Rossi Sebastiano, Davide Cusumano, Maria Grazia Bruzzone, Ferruccio Panzica, Laura Fariselli
OBJECTIVE: Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide non-invasive localization of eloquent brain areas for pre-surgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. METHODS: Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex prior radiosurgery. MEG data were acquired during a visually cued hand motor-task...
September 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28941937/exploiting-homing-abilities-of-cell-carriers-targeted-delivery-of-nanoparticles-for-cancer-therapy
#13
REVIEW
Pamela Tiet, Jacob Berlin
Off target toxicities is one of the hallmarks of conventional chemotherapy as only a tiny percentage of the injected dose actually reaches the tumor(s). Numerous strategies have been employed in attempts to achieve targeted therapeutic delivery to tumors. One strategy that has received immense attention has been the packaging of these chemotherapeutics into nanoparticles and relying on the enhanced permeation and retention (EPR) effect for targeting. However, few, if any, nanoformulations have been used clinically that actually show enhanced drug delivery to tumors...
September 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28941667/advances-and-highlights-in-allergen-immunotherapy-on-the-way-to-sustained-clinical-and-immunologic-tolerance
#14
Margot Berings, Cagatay Karaaslan, Can Altunbulakli, Philippe Gevaert, Mübeccel Akdis, Claus Bachert, Cezmi A Akdis
Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation and reporting have been significantly developed. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike...
September 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28941230/effects-of-rumen-protected-pantothenate-supplementation-on-lactation-performance-ruminal-fermentation-nutrient-digestion-and-blood-metabolites-in-dairy-cows
#15
Wang Cong, Liu Qiang, Li He Qiong, Wu Xiao Xu, Gang Guo, Wen Jie Huo, Pei Cai Xia, Zhang Yan Li, Zhang Shuan Lin
BACKGROUND: Lactation performance of dairy cow has considerably increased with animal breeding and management improvement in recent years. Ruminal net synthesized pantothenic acid is insufficient to meet the requirement of high producing dairy cows. The objective was to investigate the effects of rumen-protected pantothenate (RPP) on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows. RESULTS: Dry matter (DM) intake tended to increase, whereas milk yields, milk fat percentage and yield, body condition score (BCS) changes and net energy output except for maintance increased linearly with increasing RPP supplementation...
September 23, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28941225/systems-pharmacology-model-of-gastrointestinal-damage-predicts-species-differences-and-optimizes-clinical-dosing-schedules
#16
Harish Shankaran, Anna Cronin, Jen Barnes, Pradeep Sharma, John Tolsma, Paul Jasper, Jerome T Mettetal
Gastrointestinal (GI) adverse events (AE) are frequently dose limiting for oncology agents, requiring extensive clinical testing of alternative schedules to identify optimal dosing regimens. Here we develop a translational mathematical model to predict these clinical AEs starting from preclinical GI toxicity data. The model structure incorporates known biology and includes stem cells, daughter cells and enterocytes. Published data including cellular numbers and division times informed the system parameters for human and rat...
September 22, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28940796/gene-activated-tissue-grafts-for-sustained-bone-morphogenetic-protein-2-delivery-and-bone-engineering-is-muscle-with-fascia-superior-to-muscle-and-fat
#17
Bin Ren, Volker M Betz, Christian Thirion, Michael Salomon, Volkmar Jansson, Peter E Müller, Oliver B Betz
BACKGROUND: Previously, we have presented an expedited strategy for sustained delivery of BMP-2 to bone lesions based on the implantation of gene activated fat and muscle fragments. The aim of the present in vitro experiments was to evaluate the potential of muscle with fascia as a BMP-2 delivering osteo-regenerative implant in comparison to fat tissue and muscle alone. METHODS: Subcutaneous fat, muscle and muscle with fascia were harvested from Fischer 344 rats...
September 21, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28940525/estimation-of-initial-phenobarbital-dosing-in-term-neonates-with-moderate-to-severe-hypoxic-ischaemic-encephalopathy-following-perinatal-asphyxia
#18
M Šíma, P Pokorná, J Hartinger, O Slanař
WHAT IS KNOWN AND OBJECTIVE: Phenobarbital is the first-line treatment of seizures in asphyxiated neonates; however, due to the high pharmacokinetic variability in this population, there is no consensus on the optimal dosage regimen. This study was conducted to identify variables that affect phenobarbital fate during routine clinical care and then to evaluate the dosage schedule that could be applied in term asphyxiated neonates with respect to achieving the target therapeutic range. METHODS: Phenobarbital pharmacokinetics was calculated based on serum concentrations measurements using one-compartmental model...
September 22, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28940520/direction-modulated-brachytherapy-dmbt-for-treatment-of-cervical-cancer-a-planning-study-with-192ir-60co-and-169yb-hdr-sources
#19
Habib Safigholi, Dae Yup Han, Shahram Mashouf, Abraam Soliman, Ali S Meigooni, Amir Owrangi, William Y Song
PURPOSE: To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192Ir, 60Co, and 169Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). MATERIALS AND METHODS: The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192Ir, 60Co, and 169Yb HDR sources in a water phantom against the literature data...
September 22, 2017: Medical Physics
https://www.readbyqxmd.com/read/28939964/dose-and-dose-rate-extrapolation-factors-for-malignant-and-non-malignant-health-endpoints-after-exposure-to-gamma-and-neutron-radiation
#20
Van Tran, Mark P Little
Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment...
September 22, 2017: Radiation and Environmental Biophysics
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