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https://www.readbyqxmd.com/read/28545202/memantine-inhibits-degradation-of-the-articular-cartilage-extracellular-matrix-induced-by-advanced-glycation-end-products-ages
#1
Jijun Zhao, Yinghao Yu, Zhaofeng Wu, Ling Wang, Wei Li
The accumulation of inflammation and cartilage damage induced by advanced glycation end products (AGEs) are important hallmarks of osteoarthritis (OA). Memantine is a clinically licensed drug used for the treatment of moderate and severe Alzheimer's disease. To date, little information has been reported regarding the effects of memantine on cartilage destruction. In this study, we investigated the protective effects of memantine on AGE-induced degradation of collagen II and aggrecans in human SW1353 chondrocytes...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28545032/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#2
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544993/muscarinic-receptor-m4-positive-allosteric-modulators-attenuate-central-effects-of-cocaine
#3
Camilla Dall, Pia Weikop, Ditte Dencker, Anna C Molander, Gitta Wörtwein, P Jeffrey Conn, Anders Fink-Jensen, Morgane Thomsen
BACKGROUND: Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis that specific muscarinic M4 receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking...
May 16, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28544933/cardiotoxic-effect-of-levofloxacin-and-ciprofloxacin-in-rats-with-without-acute-myocardial-infarction-impact-on-cardiac-rhythm-and-cardiac-expression-of-kv4-3-kv1-2-and-nav1-5-channels
#4
Ahmed M Abdelrady, Sawsan A Zaitone, Noha E Farag, Manal S Fawzy, Yasser M Moustafa
Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB...
May 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28544930/neural-oscillations-demonstrate-that-general-anesthesia-and-sedative-states-are-neurophysiologically-distinct-from-sleep
#5
REVIEW
Oluwaseun Akeju, Emery N Brown
General anesthesia is a man-made neurophysiological state comprised of unconsciousness, amnesia, analgesia, and immobility along with maintenance of physiological stability. Growing evidence suggests that anesthetic-induced neural oscillations are a primary mechanism of anesthetic action. Each anesthetic drug class produces distinct oscillatory dynamics that can be related to the circuit mechanisms of drug action. Sleep is a naturally occurring state of decreased arousal that is essential for normal health...
May 22, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28544682/hypertension-induced-by-tyrosine-kinase-inhibitors-for-the-treatment-of-renal-cell-carcinoma-in-hemodialysis-patients-a-single-center-experience-and-review-of-the-literature
#6
Kentaro Nakai, Hideki Fujii, Keiji Kono, Shunsuke Goto, Shinichi Nishi
Malignancy is a major cause of mortality in dialysis patients. Although molecular-targeted anticancer drugs, including tyrosine-kinase inhibitors, are used for advanced renal cell carcinoma treatment, there are few reports on their effectiveness and safety in dialysis patients. Renal cell carcinoma dialysis patients treated at our hospital from 2010 to 2013 participated in this study. Thirteen patients were treated with tyrosine-kinase inhibitors and 15 patients with surgery only (control group). During treatment, blood pressure changes and dry weight reduction tended to be greater in the tyrosine-kinase inhibitor group than in controls...
May 23, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28544639/biomimetic-model-of-tumor-microenvironment-on-microfluidic-platform
#7
Minhwan Chung, Jungho Ahn, Kyungmin Son, Sudong Kim, Noo Li Jeon
The "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in-depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544619/design-and-synthesis-of-some-acridine-piperazine-hybrids-for-the-improvement-of-cognitive-dysfunction
#8
Anuradha Sharma, Poonam Piplani
A novel series of hybrid molecules (5a-5m) was designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against cognitive dysfunction. Heterocyclic moieties acridine and piperazine were conjugated with suitable linkers in a single scaffold and the structures of the target compounds were confirmed by IR, (1) H NMR, (13) C NMR and LC-MS analysis. The pharmacological activity of synthesized compounds was evaluated using behavioral models of amnesia viz. step down passive avoidance and elevated plus maze at a dose 0...
May 25, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544603/metabolic-reprogramming-of-macrophages-exposed-to-silk-poly-lactic-co-glycolic-acid-and-silica-nanoparticles
#9
Raquel Saborano, Thidarat Wongpinyochit, John D Totten, Blair F Johnston, F Philipp Seib, Iola F Duarte
Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications...
May 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#10
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28544534/time-to-event-analysis-of-polatuzumab-vedotin-induced-peripheral-neuropathy-to-assist-in-the-comparison-of-clinical-dosing-regimens
#11
D Lu, W R Gillespie, S Girish, P Agarwal, C Li, J Hirata, Y-W Chu, M Kagedal, L Leon, V Maiya, J Y Jin
Polatuzumab vedotin, an antibody-drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade ≥2 peripheral neuropathy (PN) of 55-72% in patients with indolent non-Hodgkin lymphoma in a phase II study, when dosed 1.8-2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time-to-event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration...
May 23, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28544386/skin-mucous-membrane-disorder-and-therapeutic-effect-of-pegylated-liposomal-doxorubicin-in-recurrent-ovarian-cancer
#12
Yuki Yamada, Ryuji Kawaguchi, Fuminori Ito, Kana Iwai, Emiko Niiro, Hiroshi Shigetomi, Yasuhito Tanase, Hiroshi Kobayashi
AIM: Hand-foot syndrome (HFS) induced by chemotherapy and molecule-targeting drugs is correlated with treatment efficacy. We conducted a retrospective analysis to evaluate the relationship between HFS and efficacy of pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer. METHODS: Patients were treated with PLD between July 2009 and May 2014. We evaluated patient characteristics, incidence of adverse events, clinical benefit (rate of complete response, partial response, and stable disease), progression-free survival, and overall survival...
May 19, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#13
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28544365/anti-aging-drugs-reduce-hypothalamic-inflammation-in-a-sex-specific-manner
#14
Marianna Sadagurski, Gillian Cady, Richard A Miller
Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Early-life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM-HET3 mice in a sex-specific way: acarbose (ACA), 17-α-estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case...
May 20, 2017: Aging Cell
https://www.readbyqxmd.com/read/28544324/albumin-templated-manganese-dioxide-nanoparticles-for-enhanced-radioisotope-therapy
#15
Longlong Tian, Qian Chen, Xuan Yi, Jiawen Chen, Chao Liang, Yu Chao, Kai Yang, Zhuang Liu
Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide (131) I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles ((131) I-HSA-MnO2 ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME)...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28544068/interstitial-fluid-pressure-a-novel-biomarker-to-monitor-photo-induced-drug-uptake-in-tumor-and-normal-tissues
#16
Sabrina Cavin, Xingyu Wang, Matthieu Zellweger, Michel Gonzalez, Michaël Bensimon, Georges Wagnières, Thorsten Krueger, Hans-Beat Ris, Fabrizio Gronchi, Jean Y Perentes
BACKGROUND: Low-dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo-induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake. MATERIAL AND METHODS: In a pleural sarcoma and adenocarcinoma rat model (n = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by intravenous Lipoplatin® (5 mg/kg) administration...
May 22, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/28544026/immobilization-and-high-platelet-count-are-associated-with-thromboembolic-complications-in-heparin-induced-thrombocytopenia
#17
Juliane Bolbrinker, Edeltraut Garbe, Antonios Douros, Matthias Huber, Elisabeth Bronder, Andreas Klimpel, Frank Andersohn, Oliver Meyer, Abdulgabar Salama, Reinhold Kreutz
PURPOSE: Immune-mediated heparin-induced thrombocytopenia (HIT type II, HIT) is a potentially serious adverse drug reaction characterized by an increased risk of venous and arterial thrombosis. This study aimed to identify risk factors associated with the development of these complications. METHODS: Our study cohort included patients with HIT assembled in our pharmacovigilance center by reports from 51 collaborating hospitals in Berlin, Germany. To identify risk factors for thromboembolic complications, patients with thromboembolic events (cases) were compared to those without thromboembolic events (controls) in a case-control design...
May 24, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28544002/biological-effects-and-osteoarthritic-disease-modifying-activity-of-small-molecule-cm-01
#18
Yubo Sun, Andrea Roberts, David R Mauerhan, Michael Cox, Edward N Hanley
Phosphocitrate inhibits cartilage degeneration, however, the prospect of phosphocitrate as an oral disease modifying drug might be limited. The purpose of this study was to investigate the biological effects and disease-modifying activity of a phosphocitrate "analogue", CM-01 (Carolinas Molecule-01), and test the hypothesis that CM-01 is a disease modifying drug for osteoarthritis therapy. The effects of CM-01 on calcium crystal-induced expression of matrix metalloproteinase-1 and interleukin-1 beta, cell-mediated calcification and production of proteoglycan by chondrocytes were examined in cell cultures...
May 25, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28543844/death-and-liver-transplantation-within-two-years-of-onset-of-drug-induced-liver-injury
#19
Paul H Hayashi, Don Rockey, Robert J Fontana, Hans L Tillmann, Neil Kaplowitz, Huiman Barnhart, Jiezhan Gu, Naga P Chalasani, K Rajender Reddy, Averell H Sherker, Jay H Hoofnagle
Drug-induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities ispoorly characterized particularly when fatalities occur > 26 weeks after DILI onset. We analyzed patients in the U.S. Drug-Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by 8 Network investigators and categorized as DILI having a primary, contributory or no role in the fatality...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543822/good-for-the-lung-but-bad-for-the-liver-garlic-induced-hepatotoxicity-following-liver-transplantation
#20
S A Shaikh, S Tischer, E K Choi, R J Fontana
WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio(®) (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio(®) was discontinued and liver enzymes normalized...
May 25, 2017: Journal of Clinical Pharmacy and Therapeutics
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