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https://www.readbyqxmd.com/read/28530164/biocompatibility-of-intensified-decellularized-equine-carotid-arteries-in-a-rat-subcutaneous-implantation-model-and-in-a-human-in-vitro-model
#1
Niklas Jeinsen, Lavinia Maegel, Danny Jonigk, Melanie Klingenberg, Axel Haverich, Mathias Wilhelmi, Ulrike Böer
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon) though this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. Here, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1-coating after subcutaneous implantation in rats for up to 12 weeks...
May 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28526350/designing-novel-bioconjugates-of-hydroxyethylcellulose-and-salicylates-for-potential-pharmaceutical-and-pharmacological-applications
#2
Khawar Abbas, Muhammad Amin, Muhammad Ajaz Hussain, Muhammad Sher, Syed Nasir Abbas Bukhari, Ibrahim Jantan, Kevin J Edgar
The present study deals with fabrication of macromolecular prodrugs (MPDs) of salicylic acid (SA) and aspirin (ASP) based on a hydrophilic cellulose ether, hydroxyethylcellulose (HEC). Degrees of substitution (DS) of SA and ASP per HEC repeating unit (HEC-RU) were achieved ranging from 0.60-2.18 and 0.53-1.50, respectively. The amphiphilic HEC-SA conjugate 2 assembled into nanowire-like structures, while HEC-ASP conjugate 6 formed nanoparticles (diameter 300-700nm) at a water/DMSO interface. After oral administration in rabbit models, conjugates 2 and 6 showed plasma half-life of 6...
May 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28520619/late-efavirenz-induced-ataxia-and-encephalopathy-a-case-series
#3
Ebrahim Variava, Farai R Sigauke, Jennifer Norman, Modiehi Rakgokong, Petudzai Muchichwa, Andre Mochan, Gary Maartens, Neil A Martinson
BACKGROUND: WHO treatment guidelines recommend efavirenz in first line antiretroviral therapy (ART). Efavirenz commonly causes early transient neuro-psychiatric adverse events. We present 20 cases with severe encephalopathy accompanied by ataxia due to efavirenz toxicity METHODS:: Consecutive HIV-infected adults taking efavirenz-containing ART admitted to Tshepong hospital, Klerksdorp, South Africa with ataxia and encephalopathy were included in this case series. RESULTS: We identified 20 women admitted to hospital with severe ataxia...
May 17, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28518054/comparison-of-three-estimators-for-determining-cyclosporine-dosing-in-infants-after-liver-transplantation%C3%A2
#4
Dzhem Farandzha, Veneta Dimitrova, Ivanka Atanasova, Lubomir Spassov, Dimiter Terziivanov
OBJECTIVE: To compare and analyze how allometrically- and linearly-scaled daily doses of cyclosporine could affect the therapeutic drug monitoring concentrations when applied to 8 infants with liver transplants. MATERIALS AND METHODS: Eight infants who underwent liver transplantations were put on twice-daily oral cyclosporine immunosuppressive regimens. After starting therapy, the adjustments of individual daily doses were determined by using therapeutic monitoring of plasma cyclosporine levels by measuring trough concentrations (C0) and concentrations at 2 hours after drug administration (C2)...
May 18, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28507111/real-life-assessment-of-the-safety-and-effectiveness-of-the-new-tablet-and-intravenous-formulations-of-posaconazole-in-the-prophylaxis-of-invasive-fungal-infections-analysis-of-343-courses
#5
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
BACKGROUND: Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infection (IFI) in patients with hematologic malignancy (HM). Delayed release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis in patients with HM. METHODS: A retrospective cohort of all consecutive adult inpatients with HM who received ≥3 days of posaconazole as tablet or intravenous from 12/1/2013-12/31/2015 for primary IFI prophylaxis at MD Anderson Cancer center...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506869/model-based-clinical-dose-optimization-for-phenobarbital-in-neonates-an-illustration-of-the-importance-of-data-sharing-and-external-validation
#6
Swantje Völler, Robert B Flint, Leo M Stolk, Pieter L J Degraeuwe, Sinno H P Simons, Paula Pokorna, David M Burger, Ronald de Groot, Dick Tibboel, Catherijne A J Knibbe
BACKGROUND: Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. METHODS: TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2...
May 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28504021/the-theory-of-dyadic-morality-reinventing-moral-judgment-by-redefining-harm
#7
Chelsea Schein, Kurt Gray
The nature of harm-and therefore moral judgment-may be misunderstood. Rather than an objective matter of reason, we argue that harm should be redefined as an intuitively perceived continuum. This redefinition provides a new understanding of moral content and mechanism-the constructionist Theory of Dyadic Morality (TDM). TDM suggests that acts are condemned proportional to three elements: norm violations, negative affect, and-importantly-perceived harm. This harm is dyadic, involving an intentional agent causing damage to a vulnerable patient (A→P)...
May 1, 2017: Personality and Social Psychology Review
https://www.readbyqxmd.com/read/28501750/development-validation-and-application-of-a-novel-liquid-chromatography-tandem-mass-spectrometry-assay-measuring-uracil-5-6-dihydrouracil-5-fluorouracil-5-6-dihydro-5-fluorouracil-%C3%AE-fluoro-%C3%AE-ureidopropionic-acid-and-%C3%AE-fluoro-%C3%AE-alanine-in-human-plasma
#8
Ottiniel Chavani, Berit Packert Jensen, R Matthew Strother, Christopher M Florkowski, Peter M George
The plasma 5,6-dihydrouracil/uracil (UH2/U) ratio is a possible phenotypic marker of dihydropyrimidine dehydrogenase (DPD) activity, hence an index of 5-fluorouracil (5-FU) response and toxicity. Studies have re-affirmed the value of 5-FU and 5,6-dihydro-5-fluorouracil (FUH2) for therapeutic drug monitoring (TDM). However, FUH2 has limited stability in plasma, necessitating expedited plasma separation and freezing, where routine compliance may not be easy. The metabolites α-fluoro-β-ureidopropionic acid (FUPA) and α-fluoro-β-alanine (FβAL) are stable in plasma and are probable candidates for TDM...
May 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28500677/optimizing-the-dose-in-cancer-patients-treated-with-imatinib-sunitinib-and-pazopanib
#9
N A G Lankheet, I M E Desar, S F Mulder, D M Burger, D M Kweekel, C M L van Herpen, W T A van der Graaf, N P van Erp
AIM: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring (TDM) based dose optimization in daily practice. METHODS: A cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow-up drug levels were measured between August 2012 and April 2016...
May 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28498155/therapeutic-drug-monitoring-to-guide-infliximab-dose-adjustment-is-associated-with-better-endoscopic-outcomes-than-clinical-decision-making-alone-in-active-inflammatory-bowel-disease
#10
Orlaith B Kelly, Sarah Oʼ Donnell, Joanne M Stempak, A Hillary Steinhart, Mark S Silverberg
BACKGROUND: Adequate infliximab (IFX) levels are associated with favorable outcomes in inflammatory bowel disease. Using therapeutic drug monitoring (TDM) to guide dosing is cost effective and associated with clinical improvement, but effect on endoscopic outcomes remains unclear. METHODS: Primary responders to IFX who underwent dose escalation (2008-2014) were reviewed. Patients with active endoscopic disease were included. Two cohorts were examined: TDM-based decision to escalate (TDM) and clinical decision (non-TDM)...
May 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28497121/implementation-of-isavuconazole-in-a-fluorescence-based-high-performance-liquid-chromatography-kit-allowing-simultaneous-detection-of-all-four-currently-licensed-mold-active-triazoles
#11
René Jørgensen, Siri Rytcher Andersen, Karen Marie Thyssen Astvad, Maiken Cavling Arendrup
Isavuconazole (ISZ) is a newly available broad-spectrum triazole agent recently approved for the treatment of both invasive aspergillosis and mucormycosis. The aim of this study was to develop a simple and reliable method for therapeutic drug monitoring (TDM) of ISZ in human plasma samples. The method involves using a kit from ChromSystems intended for TDM of itraconazole (ITZ), posaconazole (PSZ), and voriconazole (VRZ) in serum/plasma for sample preparation and high-performance liquid chromatography, using fluorescence detection with emission and excitation wavelengths set to 261 and 366 nm, respectively...
May 2017: MSphere
https://www.readbyqxmd.com/read/28490046/rapid-homogeneous-immunoassay-to-quantify-gemcitabine-in-plasma-for-therapeutic-drug-monitoring
#12
Daniel Kozo, Matt W Ross, Justin Jarrah, Michael Barrett, Rebecca L Harney, Jodi B Courtney, Irina Baburina, Julianne L Holleran, Jan H Beumer, Godefridus J Peters, Richard J Honeywell, Salvatore J Salamone
BACKGROUND: Gemcitabine (2',2'-difluoro-2'-deoxycytidine) is a nucleoside analog used as a single agent and in combination regimens for the treatment of a variety of solid tumors. Several studies have shown a relationship between gemcitabine peak plasma concentration (Cmax) and hematological toxicity. An immunoassay for gemcitabine in plasma was developed and validated to facilitate therapeutic drug monitoring (TDM) by providing an economical, robust method for automated chemistry analyzers...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28489727/pharmacology-of-thiopurine-therapy-in-inflammatory-bowel-disease-and-complete-blood-cell-count-outcomes-a-five-year-database-study
#13
Berrie Meijer, Abraham J Wilhelm, Chris Jj Mulder, Gerd Bouma, Adriaan A van Bodegraven, Nanne Kh de Boer
BACKGROUND: Thiopurines Are The Prerequisite For Immunomodulation In Inflammatory Bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites...
May 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28486309/rationale-for-therapeutic-drug-monitoring-of-biopharmaceuticals-in-inflammatory-diseases
#14
Gilles Paintaud, Christophe Passot, David Ternant, Bertolotto Antonio, Theodora Bejan-Angoulvant, Dora Pascual-Salcedo, Denis Mulleman
Biopharmaceuticals bring together a number of specific characteristics as compared with other drugs. However, as done for most drugs, an individual adjustment of their dose may be necessary. Similar to "chemical" drugs, biopharmaceuticals used in immuno-inflammatory diseases have a rather narrow therapeutic range, lack good early clinical or biological marker of response, have variable pharmacokinetics, and their serum concentration are most often related with response. Monoclonal antibodies (mAbs) have additional specific sources of pharmacokinetic variability...
May 5, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28480861/development-of-the-g-c-m-s-m-s-method-for-qualitative-and-quantitative-determination-of-clozapine-in-human-blood
#15
K Sivsivadze, M Jokhadze, P Tushurashvili, T Murtazashvili, N Imnadze
A simple, rapid, selective, sensitive gas chromatography-mass spectrometry (GC-MS/MS) method was developed and validated for the determination of clozapine in human blood. For isolation was used solid phase extraction. The calibration standards range was 5-1500ng/mL. Analysis was carried out on a gas chromatograph Agilent 7000A Quadrupole GC-MS/MS. GC run conditions - capillary column HP-5MS, 30m × 0.25mm, coated with a 0.25μm film, column temperature from 50°C to 305°C with an increase of 10°C/min; the injection port and the transfer line temperature were 310°C; carrier gas - helium at flow rate of 1...
March 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28473246/towards-therapeutic-drug-monitoring-of-everolimus-in-cancer-results-of-an-exploratory-study-of-exposure-effect-relationship
#16
Marine Deppenweiler, Sabrina Falkowski, Franck Saint-Marcoux, Caroline Monchaud, Nicolas Picard, Marie-Laure Laroche, Nicole Tubiana-Mathieu, Laurence Venat-Bouvet, Pierre Marquet, Jean-Baptiste Woillard
INTRODUCTION: Therapeutic drug monitoring (TDM) of everolimus is not performed in oncology and no trough level (C0) target has been yet defined. The aim of this study was to determine everolimus C0 target for toxicity and efficacy. MATERIALS AND METHODS: Clinical, biological and radiologic data from 54 patients were collected. Toxicity event was defined by termination, temporary interruption and/or dose reduction of everolimus while efficacy was defined as progression-free survival...
May 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28467590/-therapeutic-drug-monitoring-of-beta-lactam-antibiotics
#17
Hana Suchánková, Zuzana Matušková, Alena Vanduchová
Therapeutic drug monitoring (TDM) is a dosage individualization strategy that helps to minimize toxicity whilst maximizing the efficacy of an agent. For many years, beta-lactam antibiotics were not considered ideal candidates for TDM due to their wide therapeutic range. Profound and difficult to predict beta-lactam pharmacokinetic variability in specific patient populations and increasing bacterial resistance suggest that reaching optimal exposures can be challenging in some clinical settings. The aims are to review the role of beta-lactam TDM, identify patients that would most likely benefit from it, summarize methods used to measure beta-lactam concentrations and outline their limitations, discuss the concentration-effect relationship and therapeutic targets and finally describe dosage adjustment strategies...
March 2017: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28460228/a-disposition-kinetic-study-of-tramadol-in-bile-duct-ligated-rats-in-perfused-rat-liver-model
#18
Zohre Esmaeili, Saeid Mohammadi, Alireza Nezami, Mohammad Reza Rouini, Yalda Hosseinzadeh Ardakani, Hoda Lavasani, Mahmoud Ghazi-Khansari
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system...
April 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28457572/analytical-interference-during-cefepime-therapeutic-drug-monitoring-in-intensive-care-patient-about-a-case-report
#19
Laurie Toullec, Julien Dupouey, Coralie Vigne, Amélie Marsot, Laurent Allanioux, Olivier Blin, Marc Leone, Romain Guilhaumou
β-lactams therapeutic drug monitoring (TDM) appears as an essential tool to ensure the achievement of pharmacokinetic-pharmacodynamic targets and prevent induced toxicity in intensive care unit patients. Indeed, those patients exhibit important pharmacokinetic variabilities that could lead to unpredictable plasma concentrations, potentially associated with poor clinical outcome, development of antibiotic resistance or increased side effects. Here, we report the case of a 48-year-old-patient admitted to intensive care unit and treated by cefepime using TDM...
March 30, 2017: Thérapie
https://www.readbyqxmd.com/read/28445850/simultaneous-quantification-of-busulfan-clofarabine-and-f-ara-a-using-isotope-labelled-standards-and-standard-addition-in-plasma-by-lc-ms-ms-for-exposure-monitoring-in-hematopoietic-cell-transplantation-conditioning
#20
Arjen M Punt, Jurgen B Langenhorst, Annelies C Egas, Jaap Jan Boelens, Charlotte van Kesteren, Erik M van Maarseveen
In allogeneic hematopoietic cell transplantation (HCT) it has been shown that over- or underexposure to conditioning agents have an impact on patient outcomes. Conditioning regimens combining busulfan (Bu) and fludarabine (Flu) with or without clofarabine (Clo) are gaining interest worldwide in HCT. To evaluate and possibly adjust full conditioning exposure a simultaneous analysis of Bu, F-ARA-A (active metabolite of Flu) and Clo in one analytical run would be of great interest. However, this is a chromatographical challenge due to the large structural differences of Bu compared to F-ARA-A and Clo...
April 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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