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Dose accumulation

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https://www.readbyqxmd.com/read/28445633/advanced-glycation-end-products-in-recent-onset-psychosis-indicate-early-onset-of-cardiovascular-risk
#1
Julia M Hagen, Arjen L Sutterland, Maarten W Koeter, Rene Lutter, Dan Cohen, Lieuwe de Haan
OBJECTIVE: Profoundly increased mortality rates in schizophrenia, largely caused by a higher risk and earlier onset of cardiovascular disease, remain a major challenge. During the human lifespan, advanced glycation end products (AGEs) accumulate, and their concentration is strongly linked to cardiovascular mortality. AGE accumulation can be accelerated by several pathways, including oxidative stress. METHODS: From March 2015 through January 2016, a case-control study including 111 patients with a recent-onset psychosis, 135 controls from a validation cohort, and 286 healthy controls was performed...
April 25, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28445187/the-effects-of-inherited-nudt15-polymorphisms-on-thiopurine-active-metabolites-in-japanese-children-with-acute-lymphoblastic-leukemia
#2
Takaya Moriyama, Rina Nishii, Ting-Nien Lin, Kentaro Kihira, Hidemi Toyoda, Nersting Jacob, Motohiro Kato, Katsuyoshi Koh, Hiroto Inaba, Atsushi Manabe, Kjeld Schmiegelow, Jun J Yang, Hiroki Hori
Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major genetic cause for MP-related bone marrow suppression, and there is increasing interest in the clinical implementation of NUDT15 genotype-guided MP dose individualization. Therefore, we sought to evaluate the effects of NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform NUDT15 genotype-guided MP dosing...
April 25, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#3
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28444596/response-surface-design-for-accumulation-of-selenium-by-different-lactic-acid-bacteria
#4
Jingpeng Yang, Yao Li, Li Zhang, Mingtao Fan, Xinyuan Wei
The accumulation of selenium (Se) by Lactobacillus delbrueckii ssp. bulgaricus (Lb) and Streptococcus thermophilus (St) at the different cultivation conditions, including initial pH, inoculum dose (%), and temperature (°C), was investigated in this work. Se enrichment efficiency was optimized using the Design-Expert software for response surface methodology on a basis of single-factor experiment. The antioxidant activities of Se-enriched Lactic acid bacteria (LAB) were also investigated. The qualitative analysis of Se-enriched LAB was performed by FT-IR spectra...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28443914/probing-the-pharmacokinetics-of-cucurbit-7-8-and-10-uril-and-a-dinuclear-ruthenium-antimicrobial-complex-encapsulated-in-cucurbit-10-uril
#5
Fangfei Li, Anil K Gorle, Marie Ranson, Kara L Vine, Robert Kinobe, Marshall Feterl, Jeffrey M Warner, F Richard Keene, J Grant Collins, Anthony I Day
The relatively non-toxic family of cucurbit[n]uril, Q[n], have shown considerable potential in vitro as drug delivery agents, with only a few examples of pharmacokinetic (PK) studies for drug⊂Q[n]. Drug-free Q[n] PK studies are the next step in determining the pharmacological applicability in their drug delivery potential. The results for the first PK and bio-distribution of drug-free (14)C-Q[7] are described for administration via intravenous (i.v.) and intraperitoneal (i.p.) dosing. A study of oral administration of drug-free (14)C-Q[8] has also been undertaken to determine the time course for the gastrointestinal tract (GIT), absorption and subsequent bio-distribution...
April 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28443372/cord-blood-as-a-potential-therapeutic-for-amyotrophic-lateral-sclerosis
#6
Svitlana Garbuzova-Davis, Jared Ehrhart, Paul R Sanberg
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival. Areas covered: Composition and in vitro and in vivo differentiation of hUCB cells and the advantages of cord blood as a source of transplant cells are discussed...
April 26, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28441716/noscapinoids-bearing-silver-nanocrystals-augmented-drug-delivery-cytotoxicity-apoptosis-and-cellular-uptake-in-b16f1-mouse-melanoma-skin-cancer-cells
#7
Naina Soni, Kiran Jyoti, Upendra Kumar Jain, Anju Katyal, Ramesh Chandra, Jitender Madan
PURPOSE: Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag(2+) nanocrystals and Red-Br-Nos-Ag(2+) nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28441609/dechlorane-plus-induces-oxidative-stress-and-decreases-cyclooxygenase-activity-in-the-blue-mussel
#8
Pierre-Luc Gagné, Marlène Fortier, Marc Fraser, Lise Parent, Cathy Vaillancourt, Jonathan Verreault
Dechlorane Plus (DP) is a chlorinated flame retardant used mainly in electrical wire and cable coating, computer connectors, and plastic roofing materials. Concentrations of DP (syn and anti isomers) are increasingly being reported in aquatic ecosystems worldwide. However, there is exceedingly little information on the exposure-related toxicity of DP in aquatic organisms, especially in bivalves. The objective of this study was to investigate the in vivo and in vitro effects of DP exposure on histopathology, lipid peroxidation (LPO) levels, cyclooxygenase (COX) activity, phagocytosis capacity and efficiency, and DNA strand breakage in the blue mussel (Mytilus edulis) following a 29days exposure (0...
April 17, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28440955/phase-1-dose-escalation-study-of-mirvetuximab-soravtansine-imgn853-a-folate-receptor-%C3%AE-targeting-antibody-drug-conjugate-in-patients-with-solid-tumors
#9
Kathleen N Moore, Hossein Borghaei, David M O'Malley, Woondong Jeong, Shelly M Seward, Todd M Bauer, Raymond P Perez, Ursula A Matulonis, Kelli L Running, Xiaoyan Zhang, Jose F Ponte, Rodrigo Ruiz-Soto, Michael J Birrer
BACKGROUND: Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors. METHODS: Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme...
April 25, 2017: Cancer
https://www.readbyqxmd.com/read/28440569/toxicity-of-silver-nanoparticles-to-arabidopsis-inhibition-of-root-gravitropism-by-interfering-with-auxin-pathway
#10
Juzhi Sun, Likai Wang, Shuang Li, Liyan Yin, Jin Huang, Chunli Chen
Impacts of polyvinylpyrrolidine-coated silver nanoparticles (PVP-AgNPs) on root gravitropism in Arabidopsis thaliana were investigated at physiological, cellular and molecular level. Our results showed that AgNPs were taken up by the root and primarily localized at the cell wall and intercellular spaces. The root gravitropism was inhibited by exposure to AgNPs, and the inhibitions in root gravitropism caused by exposure to AgNPs exhibited a dose-response relationship. Auxin accumulation was reduced in the root tips due to exposure to AgNPs...
April 25, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28440559/a-phase-2-study-of-mocetinostat-a-histone-deacetylase-inhibitor-in-relapsed-or-refractory-lymphoma
#11
Connie L Batlevi, Michael Crump, Charalambos Andreadis, David Rizzieri, Sarit E Assouline, Susan Fox, Richard H C van der Jagt, Amanda Copeland, Diane Potvin, Richard Chao, Anas Younes
Deregulation of histone deacetylase (HDAC) is important in the pathogenesis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Mocetinostat, an isotype-selective HDAC inhibitor, induces accumulation of acetylated histones, cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL. Seventy-two patients received mocetinostat (starting doses: 70-110 mg TIW, 4-week cycles). The best overall response rate (95% CI) was 18·9% (7·2, 32·2) for the DLBCL cohort (n = 41), and 11·5% (1·7, 20·7) for the FL cohort (n = 31)...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28440392/suppressive-role-of-diallyl-trisul%C3%AF-de-in-the-activated-platelet-mediated-hematogenous-metastasis-of-mda-mb-231-human-breast-cancer-cells
#12
Yuping Liu, Yang Zhao, Yingyu Wang, Pingting Zhu, Zhonghong Wei, Siliang Wang, Li Tao, Zhaoguo Liu, Hongyan Wu, Xiaobo Sheng, Yin Lu
Accumulating evidence has indicated that garlic consumption may reduce the risk of developing several types of cancer, and extensive studies have revealed the effects of its bioactive component, diallyl trisulfide (DATS), on the proliferation and apoptosis of tumor cells. The present study was undertaken to examine whether DATS affects hematogenous metastasis. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we attempted to demonstrate the role of DATS in the metastatic behavior of MDA-MB-231 human breast cancer cells, which were co-incubated with activated platelets...
April 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440368/mangiferin-functionalized-radioactive-gold-nanoparticles-mgf-198-aunps-in-prostate-tumor-therapy-green-nanotechnology-for-production-in-vivo-tumor-retention-and-evaluation-of-therapeutic-efficacy
#13
A Y Al-Yasiri, M Khoobchandani, C S Cutler, L Watkinson, T Carmack, C J Smith, M Kuchuk, S K Loyalka, A B Lugão, K V Katti
We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-(198)AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs...
April 25, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28438604/first-reported-chinese-case-of-guanidinoacetate-methyltransferase-deficiency-in-a-4-year-old-child
#14
Weihua Sun, Yi Wang, Zhen Zu, Jiang Yi, Wei Lu, Huijun Wang, Bingbing Wu, Ping Zhang, Xiaomin Peng, Hao Zhou
Guanidinoacetate methyltransferase (GAMT) deficiency is a rare inherited disorder characterized by creatine (Cr) depletion and guanidinoacetate (GAA) accumulation in body fluids. We report the first identified Chinese case, diagnosed in a 4-year-old girl with onset of global developmental. Low Cr and high GAA levels were detected in her serum and urine, and low Cr level in her brain. Compound heterozygous variants in GAMT gene were found, including a previously reported variant at c.491dupG which was inherited from her mother and a novel variant at c...
April 21, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28437606/transfer-study-of-silver-nanoparticles-in-poultry-production
#15
Federica Gallocchio, Giancarlo Biancotto, Veronica Cibin, Carmen Losasso, Simone Belluco, Ruud Peters, Greet van Bemmel, Claudia Cascio, Stefan Weigel, Peter Tromp, Federica Gobbo, Salvatore Catania, Antonia Ricci
Silver nanoparticles (AgNPs) are of interest due to their antimicrobial activity and are seen as potential candidates to replace antibiotics in animal husbandry. A few studies have focused on this new application, but they lack any considerations about residual accumulation of AgNPs in edible animal tissues and animal products. In this research a 22-days in vivo study was carried out by oral administration of 20 nm spherical PVP coated AgNPs to hens. Six doses of approximately 1 mg kg-1 of AgNPs-PVP each were administered to animals throughout the experimentation...
April 27, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28437481/firemaster%C3%A2-550-and-its-components-isopropylated-triphenyl-phosphate-and-triphenyl-phosphate-enhance-adipogenesis-and-transcriptional-activity-of-peroxisome-proliferator-activated-receptor-ppar%C3%AE-on-the-adipocyte-protein-2-ap2-promoter
#16
Emily W Y Tung, Shaimaa Ahmed, Vian Peshdary, Ella Atlas
Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5-tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects and may exert these effects through PPARγ activation. Using murine 3T3-L1 preadipocytes, we investigated the detailed expression of transcription factors and adipogenic markers in response to FM550 and its components...
2017: PloS One
https://www.readbyqxmd.com/read/28437175/pharmacokinetics-and-safety-of-travoprost-0-004-ophthalmic-solution-preserved-with-polyquad-in-pediatric-patients-with-glaucoma
#17
Erin Stahl, Dominique Bremond-Gignac, Theresa Landry, Mike Curtis, Kinfemichael Gedif, Sami Al Shahwan, El Roy Dixon
PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004% preserved with Polyquad(®) (TRAVATAN(®)) in pediatric patients with glaucoma or ocular hypertension. METHODS: This was a phase 1, open-label, multicenter clinical study of patients aged ≥2 months to <18 years. Patients received daily administration of travoprost 0.004% preserved with Polyquad in both eyes for 7 days. Plasma samples were collected 30 min before the final dose and at 10, 20, 40, and 80 min postdose...
February 24, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28436921/feasibility-study-of-entrance-and-exit-dose-measurements-at-the-contra-lateral-breast-with-alanine-electron-spin-resonance-dosimetry-in-volumetric-modulated-radiotherapy-of-breast-cancer
#18
Daniela M Wagner, Petra Huettenrauch, Mathias Anton, Philip von Voigts-Rhetz, Klemens Zink, Hendrik Wolff
PURPOSE: The Physikalisch-Technische Bundesanstalt (PTB) has established a secondary standard measurement system for the dose to water, DW, based on alanine/ ESR (Anton et. al. 2013). The aim of this study was to test the established measurements system for out of field measurements inpatient with breast cancer. METHOD AND MATERIALS: A set of five alanine pellets were affixed to each patients` skin at the contra lateral breast beginning at the sternum and extending over the mammilla to the distal surface...
April 24, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28436172/indaziflam-a-new-cellulose-biosynthesis-inhibiting-herbicide-provides-long-term-control-of-invasive-winter-annual-grasses
#19
Derek J Sebastian, Margaret B Fleming, Eric L Patterson, James R Sebastian, Scott J Nissen
BACKGROUND: Indaziflam (Esplanade™, Bayer CropScience) is a cellulose biosynthesis inhibiting (CBI) herbicide that is a unique mode of action for resistance management and has broad spectrum activity at low application rates. This research further explores indaziflam's activity on monocotyledons and dicotyledons, and evaluates indaziflam's potential for restoring non-crop sites infested with invasive winter annual grasses. RESULTS: Treated Arabidopsis, downy brome, feral rye, and kochia were all susceptible to indaziflam in a dose-dependent manner...
April 24, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28435218/pharmacokinetics-and-safety-of-olopatadine-hydrochloride-0-77-in-healthy-subjects-with-asymptomatic-eyes-data-from-2-independent-clinical-studies
#20
Edward Meier, Abhijit Narvekar, Ganesh R Iyer, Harvey B DuBiner, Apinya Vutikullird, David Wirta, Kenneth Sall
PURPOSE: To assess the pharmacokinetics and safety of hydrochloride ophthalmic solution 0.77% olopatadine from 2 independent (Phase I and Phase III, respectively) clinical studies in healthy subjects. MATERIALS AND METHODS: The Phase I, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥18 years old (N=36) to assess the systemic pharmacokinetics of olopatadine 0.77% following single- and multiple-dose exposures. The Phase III, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥2 years old (N=499) to evaluate long-term ocular safety of olopatadine 0...
2017: Clinical Ophthalmology
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