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https://www.readbyqxmd.com/read/27915198/a-new-approach-to-the-rapid-separation-of-isomeric-compounds-in-a-silybum-marianum-extract-using-uhplc-core-shell-column-with-f5-stationary-phase
#1
Jakub Fibigr, Dalibor Šatínský, Petr Solich
In this paper, a new ultra-high performance liquid chromatography (UHPLC) method using a core-shell column with a pentafluorophenyl stationary phase for separation of seven active compounds of a Silybum marianum extract was developed and validated. Silymarin, an extract of Silybum marianum, is known for its abilities to protect the liver from toxic substances, hepatitis therapy, and anti-tumour activity. Silymarin is currently being widely used in commercial preparations and herbal teas. Separation of seven compounds contained in the Silybum marianum extract (taxifolin, silychristin, silydianin, silybin A, silybin B, isosilybin A, isosilybin B) and other substances occurring in real samples was performed on the Kinetex 1...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27913847/patulin-transformation-products-and-last-intermediates-in-its-biosynthetic-pathway-e-and-z-ascladiol-are-not-toxic-to-human-cells
#2
Joanna Tannous, Selma P Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, André El Khoury, Ali Atoui, Ting Zhou, Roger Lteif, Isabelle P Oswald, Olivier Puel
Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913221/role-of-the-inflammasome-in-acetaminophen-induced-liver-injury-and-acute-liver-failure
#3
REVIEW
Benjamin L Woolbright, Hartmut Jaeschke
Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has occurred recently in the literature over whether or not there exists a second phase of injury, mediated by inflammatory processes...
November 29, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#4
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27912738/hepatoprotective-activity-of-lepidium-sativum-seeds-against-d-galactosamine-lipopolysaccharide-induced-hepatotoxicity-in-animal-model
#5
Mohammad Raish, Ajaz Ahmad, Khalid M Alkharfy, Syed Rizwan Ahamad, Kazi Mohsin, Fahad I Al-Jenoobi, Abdullah M Al-Mohizea, Mushtaq Ahmad Ansari
BACKGROUND: Fulminant hepatic failure (FHF) is clinical syndrome with very poor prognosis and high mortality there is urgent need for the development of safe and non-toxic hepatoprotective agents for the adequate management of hepatitis. Hepatoprotective effect of the Lepidium sativum ethanolic extract (LSEE) was assessed by D-galactosamine-induced/lipopolysaccharide (400 mg/kg and 30 μg/kg) liver damage model in rats. METHODS: Hepatoprotective activity of LSEE (150 and 300 mg/kg) and silymarin on D-GalN/LPS induced FHF in rat was assessed using several liver function enzyme parameters...
December 3, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27910896/methylmercury-induces-the-expression-of-tnf-%C3%AE-selectively-in-the-brain-of-mice
#6
Miyuki Iwai-Shimada, Tsutomu Takahashi, Min-Seok Kim, Masatake Fujimura, Hitoyasu Ito, Takashi Toyama, Akira Naganuma, Gi-Wook Hwang
Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#7
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27908259/a-novel-liquid-chromatography-tandem-mass-spectrometry-method-for-the-estimation-of-bilirubin-glucuronides-and-its-application-to-in-vitro-enzyme-assays
#8
Siva Prasad Putluru, Murali Krishna Matta, Deepak Ahire, Murali Subramanian, Michael Sinz, Sandhya Mandlekar
Bilirubin is a toxic waste product of metabolism, eliminated mainly through UGT1A1 mediated conjugation to mono- and di-glucuronides. Due to the potentially low Km value of bilirubin glucuronidation, the quantitative sensitivity obtained with most UV/visible light detection methods are not sufficient to accurately calculate UGT1A1 enzyme kinetics and inhibition properties of new chemical entities at low bilirubin concentrations. In addition, bilirubin, as well as its metabolites, are unstable during sample preparation and bioanalysis...
November 24, 2016: Drug Metabolism Letters
https://www.readbyqxmd.com/read/27907063/evaluation-of-focal-liver-reaction-after-proton-beam-therapy-for-hepatocellular-carcinoma-examined-using-gd-eob-dtpa-enhanced-hepatic-magnetic-resonance-imaging
#9
Shigeyuki Takamatsu, Kazutaka Yamamoto, Yoshikazu Maeda, Mariko Kawamura, Satoshi Shibata, Yoshitaka Sato, Kazuki Terashima, Yasuhiro Shimizu, Yuji Tameshige, Makoto Sasaki, Satoko Asahi, Tamaki Kondou, Satoshi Kobayashi, Osamu Matsui, Toshifumi Gabata
BACKGROUND: Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage...
2016: PloS One
https://www.readbyqxmd.com/read/27906723/safety-and-outcome-measures-of-first-in-human-intraperitoneal-%C3%AE-radioimmunotherapy-with-212pb-tcmc-trastuzumab
#10
Ruby F Meredith, Julien J Torgue, Tania A Rozgaja, Eileen P Banaga, Patty W Bunch, Ronald D Alvarez, J Michael Straughn, Michael C Dobelbower, Andrew M Lowy
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome...
November 30, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27904813/glycyrrhetinic-acid-might-increase-the-nephrotoxicity-of-bakuchiol-by-inhibiting-cytochrome-p450-isoenzymes
#11
Aifang Li, Nana Ma, Zijing Zhao, Mei Yuan, Hua Li, Qi Wang
BACKGROUND: Licorice, a popular traditional Chinese medicine (TCM), is widely used to moderate the effects (detoxification) of other herbs in TCM and often combined with Fructus Psoraleae. However, the classical TCM book states that Fructus Psoraleae is incompatible with licorice; the mechanism underlying this incompatibility has not been identified. Glycyrrhetinic acid (GA), the active metabolite of licorice, may increase the toxicity of bakuchiol (BAK), the main chemical ingredient in Psoralea corylifolia, by inhibiting its detoxification enzymes CYP450s...
2016: PeerJ
https://www.readbyqxmd.com/read/27903184/microinvasive-tumor-endoresection-in-combination-with-ocular-stereotactic-radiosurgery
#12
Oleg A Sinyavskiy, Roman L Troyanovsky, Pavel I Ivanov, Alexandr S Golovin, Andrey V Tibilov, Svetlana N Solonina, Anna M Astapenko, Irina S Zubatkina
OBJECTIVE The use of Gamma Knife radiosurgery (GKRS) as monotherapy in the treatment of uveal melanoma (UM) allows clinicians to achieve high local tumor control with low recurrence but does not prevent secondary enucleation due to glaucoma in cases of large tumors. The authors analyzed indications for tumor endoresection (ER), the time interval between irradiation and surgery, and the features and results of performing ER for UM after GKRS. METHODS Thirty-seven patients between 28 and 78 years of age (16 male and 11 female patients) with UM underwent GKRS with a dose of 70 to 80 Gy that was applied to the center of the tumor with complete immobilization of the eye during the procedure...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27903079/preclinical-evaluation-of-a-replication-deficient-recombinant-adenovirus-serotype-5-vaccine-expressing-guanylate-cyclase-c-and-the-padre-t-helper-epitope
#13
Adam Eugene Snook, Trevor R Baybutt, Terry Hyslop, Scott Arthur Waldman
There is an unmet need for improved therapeutics for colorectal cancer, the second leading cause of cancer mortality worldwide. Adjuvant chemotherapy only marginally improves survival in some patients, and has no benefit in others, underscoring the clinical opportunity for novel immunotherapeutic approaches to improve survival in colorectal cancer. In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity...
November 30, 2016: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/27901175/adme-studies-and-preliminary-safety-pharmacology-of-ldt5-a-lead-compound-for-the-treatment-of-benign-prostatic-hyperplasia
#14
F Noël, J B Nascimento-Viana, L A S Romeiro, R O Silva, L F N Lemes, A S Oliveira, T B S Giorno, P D Fernandes, C L M Silva
This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells...
2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27901159/a-portable-and-reconfigurable-multi-organ-platform-for-drug-development-with-onboard-microfluidic-flow-control
#15
J R Coppeta, M J Mescher, B C Isenberg, A J Spencer, E S Kim, A R Lever, T J Mulhern, R Prantil-Baun, J C Comolli, J T Borenstein
The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform...
November 30, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27900057/in-vitro-and-in-vivo-inhibition-of-tumor-cell-viability-by-combined-dihydroartemisinin-and-doxorubicin-treatment-and-the-underlying-mechanism
#16
Xiang Tai, Xiao-Bei Cai, Zhang Zhang, Rui Wei
The natural extract artemisinin and its derivatives have good anticancer activity. The present study aimed to investigate the in vitro inhibitory effects of combined dihydroartemisinin (DHA) and doxorubicin (DOX) treatment on a variety of tumor cell lines (HeLa, OVCAR-3, MCF-7, PC-3 and A549), as well as the underlying mechanisms. In addition, the in vivo effects of DHA and DOX were evaluated using a mouse HeLa tumor model. The HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells were treated with a combination of DHA and DOX, and the effect on cell viability was detected by Cell Counting kit-8...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899981/the-effect-and-clinical-efficacy-of-lienal-polypeptide-injection-combined-with-folfox-chemotherapy-regimen-in-colon-cancer-patients
#17
Juan Zhou, Guoping Niu, Yunfeng Pei, Chunping Cao, Chen Ding, Guangming Sun, Jing Guo, Yong Liu, Yang Yu
The aim was to investigate the clinical efficacy and immunomodulatory effect of lienal polypeptide injection combined with postoperative FOLFOX chemotherapy regimen in colon cancer patients. A total of 84 colon cancer patients were selected between January, 2014 and December, 2015. The selected patients were randomly divided into the observation (42 patients) and control (42 patients) groups. The observation group patients were treated with FOLFOX chemotherapy regimen combined with lienal polypeptide, whereas, the control group patients were treated with FOLFOX chemotherapeutic regimen only...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896850/zebrafish-larva-as-a-reliable-model-for-in-vivo-assessment-of-membrane-remodeling-involvement-in-the-hepatotoxicity-of-chemical-agents
#18
Normand Podechard, Martine Chevanne, Morgane Fernier, Arnaud Tête, Aurore Collin, Doris Cassio, Olivier Kah, Dominique Lagadic-Gossmann, Odile Sergent
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896586/effect-of-berberine-on-the-ratio-of-high-molecular-weight-adiponectin-to-total-adiponectin-and-adiponectin-receptors-expressions-in-high-fat-diet-fed-rats
#19
Yue-Yue Wu, Ying Zha, Jun Liu, Fang Wang, Jiong Xu, Zao-Ping Chen, He-Yuan Ding, Li Sheng, Xiao-Jie Han
OBJECTIVE: To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. METHODS: Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg(-1)·day(-1) BBR (HF+LBBR group) and 380 mg·kg(-1)·day(-1) BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh)...
November 17, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27895494/ercc1-and-xrcc1-but-not-xpa-single-nucleotide-polymorphisms-correlate-with-response-to-chemotherapy-in-endometrial-carcinoma
#20
Liang Chen, Mei-Mei Liu, Hui Liu, Dan Lu, Xiao-Dan Zhao, Xue-Jing Yang
Our study aimed to investigate the correlation between single nucleotide polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy and prognosis of endometrial carcinoma. Our study included 108 patients with endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1 rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Then the chemotherapy efficacy and toxic effects of the patients were assessed. The genotype and allele frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly different from that in the control group (all P<0...
2016: OncoTargets and Therapy
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