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https://www.readbyqxmd.com/read/28343282/effective-chemotherapy-of-heterogeneous-and-drug-resistant-early-colon-cancers-by-intermittent-dose-schedules-a-computer-simulation-study
#1
David E Axelrod, Sudeepti Vedula, James Obaniyi
PURPOSE: The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function...
March 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28343074/cratoxy-formosum-leaf-extract-inhibits-proliferation-and-migration-of-human-breast-cancer-mcf-7-cells
#2
Benjaporn Buranrat, Nootchanat Mairuae, Ampa Konsue
In this study we investigated how Cratoxy formosum (CF) leaf extract affects the viability and migration of human breast cancer cells including the mechanism(s) responsible. Our results showed that CF leaf extract strongly induced MCF-7 cell death in a concentration- and time-dependent manner, with IC50 values of 85.70±4.52μg/mL and 53.74±3.02μg/mL at 24h and 48h, respectively. Additionally, CF leaf extract potentiated the activity of 4 anticancer drugs with the greatest synergy occurring between CF and 5-FU...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28343071/analgesia-effect-of-baicalein-against-ntg-induced-migraine-in-rats
#3
Xiao-Fan Zhang, Wen-Jun Zhang, Cui-Lan Dong, Wan-Li Hu, Yu-Yao Sun, Yarigui Bao, Chun-Feng Zhang, Chang-Run Guo, Chong-Zhi Wang, Chun-Su Yuan
BACKGROUND: Migraine is a complex nervous system disease characterized by typical throbbing and unilateral headache, which causes severe healthy and social issues worldwide. The purpose of this study was to investigate the effect of baicalein (BAI) on the treatment of migraine. MATERIAL AND METHODS: Twenty-four rats were randomly divided equally into four groups, including a blank group, model group, positive group (ibuprofen tablets 82mg/kg), and BAI group (60mg/kg)...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28342981/mechanisms-of-in-vivo-release-of-triamcinolone-acetonide-from-plga-microspheres
#4
Amy C Doty, David G Weinstein, Keiji Hirota, Karl F Olsen, Rose Ackermann, Yan Wang, Stephanie Choi, Steven P Schwendeman
Little is known about the underlying effects controlling in vitro-in vivo correlations (IVIVCs) for biodegradable controlled release microspheres. Most reports of IVIVCs that exist are empirical in nature, typically based on a mathematical relationship between in vitro and in vivo drug release, with the latter often estimated by deconvolution of pharmacokinetic data. In order to improve the ability of in vitro release tests to predict microsphere behavior in vivo and develop more meaningful IVIVCs, the in vivo release mechanisms need to be characterized...
March 22, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28342897/dose-response-effect-of-acute-phencyclidine-on-functional-connectivity-and-dopamine-levels-and-their-association-with-schizophrenia-like-symptom-classes-in-rat
#5
Jaakko Paasonen, Raimo A Salo, Jouni Ihalainen, Juuso V Leikas, Katja Savolainen, Marko Lehtonen, Markus M Forsberg, Olli Gröhn
Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5.0 mg/kg) on rat brain connectivity and detect markers for different SCZ-like symptoms. Pharmacological functional magnetic resonance imaging (phMRI) and microdialysis were used to investigate PCP-induced effects on functional connectivity (FC) and dopamine levels, respectively...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342892/comparison-of-three-cell-based-drug-screening-platforms-for-hsv-1-infection
#6
Leonardo D'Aiuto, Kelly Williamson, Peter Dimitrion, James McNulty, Carla E Brown, Chanti Babu Dokuburra, Alexander J Nielsen, Wen Jing Lin, Paolo Piazza, Mark E Schurdak, Joel Wood, Robert H Yolken, Paul R Kinchington, David C Bloom, Vishwajit L Nimgaonkar
Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS)...
March 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28342858/aqueous-extract-from-leaf-of-artocarpus-altilis-provides-cardio-protection-from-isoproterenol-induced-myocardial-damage-in-rats-negative-chronotropic-and-inotropic-effects
#7
Chukwuemeka Nwokocha, Javier Palacios, Mario J Simirgiotis, Jemesha Thomas, Magdalene Nwokocha, Lauriann Young, Rory Thompson, Fredi Cifuentes, Adrian Paredes, Rupika Delgoda
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. MATERIAL AND METHODS: Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-hour period...
March 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28342783/effect-of-storage-on-the-physical-stability-of-thin-polymethacrylate-perphenazine-films
#8
Kristiina Korhonen, Elina Smolander, Ossi Korhonen, Jarkko Ketolainen, Riikka Laitinen
We evaluated the physical stability of thin polymethacrylate-drug films under three different storage conditions by X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, polarized light microscopy, and Fourier transform infrared spectroscopy. Mechanical properties i.e. elongation, mechanical strength, and in vitro drug release from the thin films were also determined during storage. The films consisted of ammonium methacrylate copolymer (RLPO)/dimethylaminoethyl methacrylate copolymer (EPO), polyvinylpyrroline (PVP)/polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus) and perphenazine (PPZ)...
March 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28342779/suppression-of-calpain-expression-by-nsaids-is-associated-with-inhibition-of-cell-migration-in-rat-duodenum
#9
Kristopher Silver, A Littlejohn, Laurel Thomas, Bhupinder Bawa, James D Lillich
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity...
March 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28342735/inhibition-of-effector-antigen-specific-t-cells-by-intradermal-administration-of-heme-oxygenase-1-inducers
#10
Thomas Simon, Julien Pogu, Séverine Rémy, Frédéric Brau, Sylvie Pogu, Maud Maquigneau, Jean-François Fonteneau, Nicolas Poirier, Bernard Vanhove, Gilles Blancho, Eliane Piaggio, Ignacio Anegon, Philippe Blancou
Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28342702/apigenin-attenuates-oxidative-stress-and-neuronal-apoptosis-in-early-brain-injury-following-subarachnoid-hemorrhage
#11
Yuwei Han, Tingting Zhang, Jingyuan Su, Yuan Zhao, Chenchen, Wang, Xiaoming Li
Apigenin (API) is a naturally occurring plant flavone that exhibits powerful antioxidant and antiapoptosis. Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The potential anti-oxidative and anti-apoptosis effects of API on EBI following SAH, however, have not been elucidated. The aim of this study was to assess whether API alleviates EBI after SAH via its anti-oxidative and anti-apoptotic effects. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 24h after SAH...
March 22, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28342673/therapeutic-use-of-bacillus-thuringiensis-in-the-treatment-of-psoroptic-mange-in-naturally-infested-new-zealand-rabbits
#12
Emmanuel Dunstand-Guzmán, Claudia Hallal-Calleros, Jorge Morales-Montor, Víctor Manuel Hernández-Velázquez, Juan José Zárate-Ramos, Kurt L Hoffman, Guadalupe Peña-Chora, Fernando Iván Flores-Pérez
Bacillus thuringiensis is a bacteria known for its bioinsecticidal toxins and it has been proposed as an alternative in the treatment of several parasites that infect domestic animals (helminths, ticks, mites). In this work, we evaluated the clinical efficiency of the Bacillus thuringiensis GP532 strain in the treatment of six rabbits naturally infested with the P. cuniculi mite. GP532 extract (10mg/ml) was applied by aspersion in both pinna, with a second application after seven days, and the therapeutic effect was measured in both qualitative and quantitative manner...
March 9, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28342455/repair-of-oxidatively-induced-dna-damage-by-dna-glycosylases-mechanisms-of-action-substrate-specificities-and-excision-kinetics
#13
REVIEW
Miral Dizdaroglu, Erdem Coskun, Pawel Jaruga
Endogenous and exogenous reactive species cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. As a result, a plethora of mutagenic and/or cytotoxic products are formed in cellular DNA. This type of DNA damage is repaired by base excision repair, although nucleotide excision repair also plays a limited role. DNA glycosylases remove modified DNA bases from DNA by hydrolyzing the glycosidic bond leaving behind an apurinic/apyrimidinic (AP) site. Some of them also possess an accompanying AP-lyase activity that cleaves the sugar-phosphate chain of DNA...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28342366/discovery-of-new-dual-ppar%C3%AE-gpr40-agonists-with-robust-antidiabetic-activity-design-synthesis-and-in-combo-drug-evaluation
#14
Sergio Hidalgo-Figueroa, Gabriel Navarrete-Vázquez, Samuel Estrada-Soto, Diana Giles-Rivas, Francisco J Alarcón-Aguilar, Ismael León-Rivera, Abraham Giacoman-Martínez, Elizabeth Miranda Pérez, Julio C Almanza-Pérez
The design of compounds 1 and 2 was based on the similar scaffold of pharmacophoric groups for PPARγ and GPR40 agonists. In order to find new compounds with improved biological activity, the current manuscript describes a new dual PPARγ-GPR40 agonist. We synthesized two compounds, which were prepared following a multistep synthetic route, and the relative mRNA expression levels of PPARγ, GLUT4, and GPR40 were quantified in cell culture, as well as insulin secretion and [Ca(2+)] intracellular levels. Compound 1 showed a 7-times increase in the mRNA expression of PPARγ, which in turn enhanced the expression levels of GLUT4 respect to control and pioglitazone...
March 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340506/neuromedin-u-alters-bioenergetics-and-expands-the-cancer-stem-cell-phenotype-in-her2-positive-breast-cancer
#15
Vanesa G Martinez, John Crown, Richard K Porter, Lorraine O'Driscoll
Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over-expression of NmU in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340477/environmental-analysis-of-typical-antibiotic-resistant-bacteria-and-args-in-farmland-soil-chronically-fertilized-with-chicken-manure
#16
Xiang Zhao, Jinhua Wang, Lusheng Zhu, Weili Ge, Jun Wang
Antibiotics and the corresponding resistant bacteria and resistance genes (ARGs) are generally considered emerging pollutants. To assess the impacts of tetracycline (TC) and sulfonamide (SA) antibiotics that are eliminated with fecaluria as drug prototypes, farmland soil used to research long-term fertilization with chicken manure was collected at four sites in Shandong Province. In this study, the rates of bacterial drug resistance to the same antibiotic decreased with an increase in the concentration of that antibiotic, and the resistance rates to TCs were lower than those to SAs...
March 21, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#17
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#18
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28340402/eslicarbazepine-acetate-as-a-therapeutic-option-in-a-patient-with-carbamazepine-induced-rash-and-hla-a-31-01
#19
Lara Kay, Laurent M Willems, Johann Philipp Zöllner, Philipp S Reif, Karl Martin Klein, Felix Rosenow, Adam Strzelczyk
Eslicarbazepine acetate (ESL) is an anticonvulsant drug approved for the treatment of focal epilepsies, and related to oxcarbazepine and carbamazepine (CBZ), which are also derivatives of the dibenzazepine family. ESL is contraindicated in patients with hypersensitivity reactions to CBZ.We report a patient with frontal lobe epilepsy responding to treatment with ESL without any serious adverse effects after developing a severe skin rash following treatment with CBZ. HLA testing revealed an HLA-A*31:01 haplotype, that increases the risk of CBZ-induced cutaneous reactions...
March 18, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28340357/ruthenium-complexes-with-phenylterpyridine-derivatives-target-cell-membrane-and-trigger-death-receptors-mediated-apoptosis-in-cancer-cells
#20
Zhiqin Deng, Pan Gao, Lianling Yu, Bin Ma, Yuanyuan You, Leung Chan, Chaoming Mei, Tianfeng Chen
Elucidation of the communication between metal complexes and cell membrane may provide useful information for rational design of metal-based anticancer drugs. Herein we synthesized a novel class of ruthenium (Ru) complexes containing phtpy derivatives (phtpy = phenylterpyridine), analyzed their structure-activity relationship and revealed their action mechanisms. The result showed that, the increase in the planarity of hydrophobic Ru complexes significantly enhanced their lipophilicity and cellular uptake...
March 18, 2017: Biomaterials
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