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https://www.readbyqxmd.com/read/28109077/simultaneous-but-not-consecutive-combination-with-folinate-salts-potentiates-5-fluorouracil-antitumor-activity-in-vitro-and-in-vivo
#1
Antonello Di, Paola Orlandi, Teresa Di, Romano Danesi, Guido Bocci
The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of the colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV) or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72h...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28108946/in-vivo-neuroimaging-and-behavioral-correlates-in-a-rat-model-of-chemotherapy-induced-cognitive-dysfunction
#2
Robert L Barry, Nellie E Byun, M Noor Tantawy, Chase A Mackey, George H Wilson, Adam J Stark, Michael P Flom, Laura C Gee, C Chad Quarles
Adjuvant chemotherapy has been used for decades to treat cancer, and it is well known that disruptions in cognitive function and memory are common chemotherapeutic adverse effects. However, studies using neuropsychological metrics have also reported group differences in cognitive function and memory before or without chemotherapy, suggesting that complex factors obscure the true etiology of chemotherapy-induced cognitive dysfunction (CICD) in humans. Therefore, to better understand possible mechanisms of CICD, we explored the effects of CICD in rats through cognition testing using novel object recognition (NOR) and contextual fear conditioning (CFC), and through metabolic neuroimaging via [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)...
January 20, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28108816/decitabine-priming-prior-to-low-dose-chemotherapy-improves-patient-outcomes-in-myelodysplastic-syndromes-raeb-a-retrospective-analysis-vs-chemotherapy-alone
#3
Li Ye, Yanling Ren, Xinping Zhou, Chen Mei, Liya Ma, Xingnong Ye, Juying Wei, Weilai Xu, Haitao Meng, Wenbin Qian, Wenyuan Mai, Yinjun Lou, Gaixiang Xu, Jiejing Qian, Yejiang Lou, Yingwan Luo, Lili Xie, Peipei Lin, Chao Hu, Jie Jin, Hongyan Tong
PURPOSE: The aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes-refractory anemia with excess of blasts (MDS-RAEB). METHODS: The current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not...
January 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28108678/anti-tb-drug-concentrations-and-drug-associated-toxicities-among-tb-hiv-coinfected-patients
#4
C Sekaggya-Wiltshire, A von Braun, A U Scherrer, Y C Manabe, A Buzibye, D Muller, B Ledergerber, U Gutteck, N Corti, A Kambugu, P Byakika-Kibwika, M Lamorde, B Castelnuovo, J Fehr, M R Kamya
BACKGROUND: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. OBJECTIVES: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. METHODS: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment...
January 19, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28108402/using-pharmacokinetic-modelling-to-improve-prescribing-practices-of-intravenous-aminophylline-in-childhood-asthma-exacerbations
#5
Lewis Cooney, Antonia McBride, Andrew Lilley, Ian Sinha, Trevor N Johnson, Daniel B Hawcutt
OBJECTIVE: To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. METHODS: Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. RESULTS: Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those <10 mg/L, and adverse effects occurred in 57%...
January 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28108284/first-line-pazopanib-in-non-clear-cell-renal-carcinoma-the-italian-retrospective-multicenter-panorama-study
#6
Sebastiano Buti, Melissa Bersanelli, Francesca Maines, Gaetano Facchini, Francesco Gelsomino, Fable Zustovich, Matteo Santoni, Elena Verri, Ugo De Giorgi, Cristina Masini, Franco Morelli, Maria Giuseppa Vitale, Teodoro Sava, Giuseppe Prati, Carmelinda Librici, Anna Paola Fraccon, Giuseppe Fornarini, Marco Maruzzo, Francesco Leonardi, Orazio Caffo
INTRODUCTION: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients. PATIENTS AND METHODS: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed...
December 29, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28108195/the-virtual-cell-based-assay-current-status-and-future-perspectives
#7
Rabea Graepel, Lara Lamon, David Asturiol, Elisabet Berggren, Elisabeth Joossens, Alicia Paini, Pilar Prieto, Maurice Whelan, Andrew Worth
In order to replace the use of animals in toxicity testing, there is a need to predict in vivo toxic doses from concentrations that cause toxicological effects in relevant in vitro systems. The Virtual Cell Based Assay (VCBA) estimates time-dependent concentration of a test chemical in the cell and cell culture for a given in vitro system. The concentrations in the different compartments of the cell and test system are derived from ordinary differential equations, physicochemical parameters of the test chemical and properties of the cell line...
January 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28107864/evaluating-the-safety-of-forsythin-from-forsythia-suspensa-leaves-by-acute-and-sub-chronic-oral-administration-in-rodent-models
#8
Zhong Han, Xia-Ling Lei, Hong Zhang, Lu Liu, Zhi-Sen Chen, Wei Yang, Zhao-Rong Lun
OBJECTIVE: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety. METHODS: Acute toxicity was determined by oral administration of a single dose of 18100 mg/kg forsythin in NIH mice. Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0, 540, 1620, and 6480 mg/kg in SD rats. RESULTS: In the acute toxicity study, mortality was not observed after 14 days...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107724/effect-of-sole-or-combined-administration-of-nitrate-and-3-nitro-1-propionic-acid-on-fermentation-and-salmonella-survivability-in-alfalfa-fed-rumen-cultures-in-vitro
#9
Alejandro Castañeda Correa, Julian Trachsel, Heather K Allen, Agustin Corral-Luna, Hector Gutierrez-Bañuelos, Pedro Antonia Ochoa-Garcia, Oscar Ruiz-Barrera, Michael E Hume, Todd R Callaway, Roger B Harvey, Ross C Beier, Robin C Anderson, David J Nisbet
Ruminal methanogenesis is a digestive inefficiency resulting in the loss of dietary energy consumed by the host and contributing to environmental methane emission. Nitrate is being investigated as a feed supplement to reduce rumen methane emissions but safety and efficacy concerns persist. To assess potential synergies of co-administering sub-toxic amounts of nitrate and 3-nitro-1-propionate (NPA) on fermentation and Salmonella survivability with an alfalfa-based diet, ruminal microbes were cultured with additions of 8 or 16mM nitrate, 4 or 12mM NPA or their combinations...
January 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28107620/chemical-interaction-of-protein-cysteine-residues-with-reactive-metabolites-of-methyleugenol
#10
Yukun Feng, Hui Wang, Qian Wang, Wenlin Huang, Ying Peng, Jiang Zheng
Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME...
January 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28107527/effects-of-the-administration-of-25-oh-vitamin-d3-in-an-experimental-model-of-chronic-kidney-disease-in-animals-null-for-1-alpha-hydroxylase
#11
Noelia Torremadé, Milica Bozic, David Goltzman, Elvira Fernandez, José M Valdivielso
The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals...
2017: PloS One
https://www.readbyqxmd.com/read/28107421/peroxiporin-expression-is-an-important-factor-for-cancer-cell-susceptibility-to-therapeutic-h2o2-implications-for-pharmacological-ascorbate-therapy
#12
Dieanira Erudaitius, Andrew Huang, Sarah Kazmi, Garry R Buettner, Victor G J Rodgers
Cancer cell toxicity to therapeutic H2O2 varies widely depending on cell type. Interestingly, it has been observed that different cancer cell types have varying peroxiporin expression. We hypothesize that variation in peroxiporin expression can alter cell susceptibility to therapeutic H2O2 concentrations. Here, we silence peroxiporin aquaporin-3 (AQP3) on the pancreatic cancer cell line MIA PaCa-2 and compare clonogenic survival response to the wild-type. The results showed a significantly higher surviving fraction in the clonogenic response for siAQP3 MIA PaCa-2 cells at therapeutic H2O2 doses (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28107093/adult-clonidine-overdose-prolonged-bradycardia-and-central-nervous-system-depression-but-not-severe-toxicity
#13
Geoffrey K Isbister, Simon P Heppell, Colin B Page, Nicole M Ryan
CONTEXT: There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults. METHODS: This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200 μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records...
January 20, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#14
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106828/bajijiasu-abrogates-osteoclast-differentiation-via-the-suppression-of-rankl-signaling-pathways-through-nf-%C3%AE%C2%BAb-and-nfat
#15
Guoju Hong, Lin Zhou, Xuguang Shi, Wei He, Haibin Wang, Qiushi Wei, Peng Chen, Longkai Qi, Jennifer Tickner, Li Lin, Jiake Xu
Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu-a natural compound derived from Morinda officinalis F. C. How-has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105753/efficacy-and-safety-of-high-dose-chemotherapy-with-autologous-stem-cell-transplantation-in-senior-versus-younger-adults-with-newly-diagnosed-multiple-myeloma
#16
Li-Wen Huang, Wendi Bacon, Constance Cirrincione, Bercedis Peterson, Gwynn Long, David Rizzieri, Keith M Sullivan, Kelly Corbet, Mitchell Horwitz, Nelson Chao, Cristina Gasparetto, Sascha A Tuchman
We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1...
January 19, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28105566/phase-i-study-of-lurbinectedin-a-synthetic-tetrahydroisoquinoline-that-inhibits-activated-transcription-induces-dna-single-and-double-strand-breaks-on-a-weekly-%C3%A3-2-every-3-week-schedule
#17
Antonio Jimeno, Manish R Sharma, Sergio Szyldergemajn, Lia Gore, David Geary, Jennifer R Diamond, Carlos Fernandez Teruel, Arturo Soto Matos-Pita, Jorge Luis Iglesias, Martin Cullell-Young, Mark J Ratain
Background Lurbinectedin administered as a 1-h intravenous infusion every 3 weeks induces neutropenia, with the nadir usually occurring during the second week. This phase I study evaluated an alternative lurbinectedin dosing schedule consisting of a 1-h infusion on days 1 and 8 every 3 weeks. Patients and methods Twenty-one patients with advanced cancer received lurbinectedin using a standard cohort dose escalation design. Results Three dose levels of 3, 4, and 5 mg of lurbinectedin were explored. The recommended phase II dose was 5 mg, with 3 of 13 patients having dose-limiting toxicity (DLT), although grade 4 neutropenia occurred in 50% of patients...
January 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28105488/effects-of-ceo2-nanoparticles-on-terrestrial-isopod-porcellio-scaber-comparison-of-ceo2-biological-potential-with-other-nanoparticles
#18
Olga Malev, Polonca Trebše, Małgorzata Piecha, Sara Novak, Bojan Budič, Miroslav D Dramićanin, Damjana Drobne
Nano-sized cerium dioxide (CeO2) particles are emerging as an environmental issue due to their extensive use in automobile industries as fuel additives. Limited information is available on the potential toxicity of CeO2 nanoparticles (NPs) on terrestrial invertebrates through dietary exposure. In the present study, the toxic effects of CeO2 NPs on the model soil organism Porcellio scaber were evaluated. Nanotoxicity was assessed by monitoring the lipid peroxidation (LP) level and feeding rate after 14-days exposure to food amended with nano CeO2...
January 19, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28104561/assessment-of-in-vitro-cardiotoxicity-of-extract-fractions-and-diterpene-alkaloids-from-aconitum-leucostomum-worosch-a-short-communication
#19
Jihong Nie, Fang Wang, Tengfei Ji, Jun Zhao, Feicui Zhao
Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C18-diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C19-diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A...
January 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28104448/metformin-and-low-dose-radiation-modulates-cisplatin-induced-oxidative-injury-in-rat-via-ppar-%C3%AE-and-mapk-pathways
#20
Heba H Mansour, Shereen M El Kiki, Shereen M Galal
: Cisplatin (CIS) is a chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. The aim of this study was to investigate the role of Peroxisome proliferator-activated receptor-gamma (PPAR-γ), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B(NFkB) in the pathogenesis of hepatic damage induced by CIS, and investigated the modulatory effect of metformin (MET) and/or low dose gamma radiation (LDR) on CIS-induced hepatotoxicity in rats...
January 16, 2017: Archives of Biochemistry and Biophysics
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