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https://www.readbyqxmd.com/read/28109179/quantitative-and-integrative-analysis-of-paracrine-hepatocyte-activation-by-non-parenchymal-cells-upon-lipopolysaccharide-induction
#1
Katharina Beuke, Frank A Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G Bode, Percy A Knolle, Ursula Kummer, Kai Breuhahn, Sven Sahle
Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumor necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of non-parenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multi-scale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#2
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109052/the-use-of-methadone-to-facilitate-opioid-weaning-in-pediatric-critical-care-patients-a-systematic-review-of-the-literature-and-meta-analysis
#3
REVIEW
Leslie A Dervan, Beryl Yaghmai, Robert Scott Watson, Fredric M Wolf
BACKGROUND: Continuous opioid infusion therapy is commonly utilized in the pediatric intensive care setting to treat pain and facilitate tolerance of invasive therapies. Transitioning to methadone is one common strategy for weaning from continuous opioid infusions, but in practice this transition can be challenging, and many children still experience iatrogenic withdrawal. AIM: We reviewed the literature to evaluate the best available evidence to guide methadone therapy in this setting, and to summarize associated adverse events...
January 20, 2017: Paediatric Anaesthesia
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/28108284/first-line-pazopanib-in-non-clear-cell-renal-carcinoma-the-italian-retrospective-multicenter-panorama-study
#5
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/28108022/evaluation-of-a-method-for-removing-cesium-and-reducing-the-volume-of-leaf-litter-from-broad-leaved-trees-contaminated-by-the-fukushima-daiichi-nuclear-accident-during-the-great-east-japan-earthquake
#6
Shigeki Harada, Mitsunori Yanagisawa
The town of Marumori in southern Miyagi Prefecture borders on Fukushima Prefecture, and following the accident at the Fukushima Daiichi nuclear power plant, there were concerns about cesium deposition in forested areas. One of the authors of this paper has continually surveyed leaf litter from the forested areas. As leaf litter may be a source of cesium contamination from the forest to downstream areas, we considered a simplified version of wet oxidation, a method previously presented by one of the authors of this study, as a technology to reduce leaf litter weight and cesium concentration, separating radioactive nuclides from non-radioactive ones, in leaf litter...
January 12, 2017: Chemosphere
https://www.readbyqxmd.com/read/28107569/use-of-higher-maximum-doses-and-infusion-rates-compared-with-those-used-in-standard-unfractionated-heparin-therapy-is-associated-with-adequate-anticoagulation-without-increased-bleeding-in-both-obese-and-nonobese-patients-with-cardiovascular-indications
#7
Catherine K Floroff, Nicole M Palm, Daniel H Steinberg, Eric R Powers, Barbara S Wiggins
STUDY OBJECTIVE: To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight-based dosing recommendations compared with an aggressive weight-based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non-ST-Segment Elevation Myocardial Infarction or unstable angina (NSTEMI/UA) or atrial fibrillation. DESIGN: Retrospective cohort study...
January 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28107357/vasopressor-use-for-severe-hypotension-a-multicentre-prospective-observational-study
#8
Francois Lamontagne, Deborah J Cook, Maureen O Meade, Andrew Seely, Andrew G Day, Emmanuel Charbonney, Karim Serri, Yoanna Skrobik, Paul Hebert, Charles St-Arnaud, Hector Quiroz-Martinez, Michaël Mayette, Daren K Heyland
BACKGROUND: The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines...
2017: PloS One
https://www.readbyqxmd.com/read/28107301/implementation-of-a-pediatric-orthopaedic-bundle-to-reduce-surgical-site-infections
#9
Jan Schriefer, James Sanders, Julie Michels, Kori Wolcott, Connor Ruddy, Jenna Hanson
Surgical site infections (SSIs) cost an estimated $27,288 per case. An analysis of the National Surgical Quality Improvement Program data at the University of Rochester Medical Center suggested that rates of SSIs could be lowered in comparison with both peers and baseline. The aim of this study was to reduce the number of SSIs to zero through the implementation of a "bundle" or a combination of practices. Meetings were held with the multidisciplinary care team that includes surgeons and staff from pediatric pharmacy, pediatric infectious diseases, anesthesia, and nursing to create a care bundle for all pediatric orthopaedic surgery patients...
January 2017: Orthopaedic Nursing
https://www.readbyqxmd.com/read/28106997/time-and-nanoparticle-concentration-affect-the-extractability-of-cu-from-cuo-np-amended-soil
#10
Xiaoyu Gao, Eleanor Spielman-Sun, Sónia Morais Rodrigues, Elizabeth A Casman, Gregory V Lowry
We assess the effect of CuO nanoparticle (NP) concentration and soil aging time on the extractability of Cu from a standard sandy soil (Lufa 2.1). The soil was dosed with CuO NP or Cu(NO3)2 at 10 mg Cu kg-1 soil (mg/kg) or 100 mg/kg total copper, then extracted using either 0.01M CaCl2 or 0.005M DTPA (pH 7.6) extraction fluids at selected times over 31 days. For 100 mg/kg CuO NP, the amount of DTPA-extractable Cu in soil increased from 3 wt% immediately after mixing to 38 wt% after 31 days. In contrast, the extractability of Cu(NO3)2 was highest initially, decreasing with time...
January 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28106903/continuous-treatment-with-lenalidomide-and-low-dose-dexamethasone-in-transplant-ineligible-patients-with-newly-diagnosed-multiple-myeloma-in-asia-subanalysis-of-the-first-trial
#11
Jin Lu, Jae H Lee, Shang-Yi Huang, Lugui Qiu, Je-Jung Lee, Ting Liu, Sung-Soo Yoon, Kihyun Kim, Zhi X Shen, Hyeon S Eom, Wen M Chen, Chang K Min, Hyo J Kim, Jeong O Lee, Jae Y Kwak, Wai Yiu, Guang Chen, Annette Ervin-Haynes, Cyrille Hulin, Thierry Facon
The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low-dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28106615/metal-artifact-reduction-in-x-ray-computed-tomography-using-computer-aided-design-data-of-implants-as-prior-information
#12
Veikko Ruth, Daniel Kolditz, Christian Steiding, Willi A Kalender
OBJECTIVES: The performance of metal artifact reduction (MAR) methods in x-ray computed tomography (CT) suffers from incorrect identification of metallic implants in the artifact-affected volumetric images. The aim of this study was to investigate potential improvements of state-of-the-art MAR methods by using prior information on geometry and material of the implant. MATERIALS AND METHODS: The influence of a novel prior knowledge-based segmentation (PS) compared with threshold-based segmentation (TS) on 2 MAR methods (linear interpolation [LI] and normalized-MAR [NORMAR]) was investigated...
January 18, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28105886/interobserver-delineation-uncertainty-in-involved-node-radiation-therapy-inrt-for-early-stage-hodgkin-lymphoma-on-behalf-of-the-radiotherapy-committee-of-the-eortc-lymphoma-group
#13
Marianne C Aznar, Theodore Girinsky, Anne Kiil Berthelsen, Berthe Aleman, Max Beijert, Martin Hutchings, Yolande Lievens, Paul Meijnders, Peter Meidahl Petersen, Deborah Schut, Maja V Maraldo, Richard van der Maazen, Lena Specht
BACKGROUND AND PURPOSE: In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definition and its impact on resulting treatment plans. MATERIALS AND METHODS: Two representative cases were selected (1: male, stage IB, localization: left axilla; 2: female, stage IIB, localizations: mediastinum and bilateral neck)...
January 20, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28105626/-effect-of-polyunsaturated-fatty-acids-%C3%AF-3-and-%C3%AF-6-on-angiogenesis-formation-in-human-gastric-cancer
#14
Jiachi Ma, Yuntao Ma, Tiankang Guo, Quan Chen, Yiping Li, He Su, Xiaochang Chen, Xiaodan Zhao, Qinjin Guo, Jianbo Qi
OBJECTIVE: To investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism. METHODS: The effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization...
January 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28105567/effects-of-oleuropein-on-pentylenetetrazol-induced-seizures-in-mice-involvement-of-opioidergic-and-nitrergic-systems
#15
Nastaran Rahimi, Bahram Delfan, Nazgol Motamed-Gorji, Ahmad R Dehpour
Oleuropein, a well-known olive polyphenol, has been shown to mediate neuroprotection in Alzheimer's disease and cerebral ischemia. We investigated the effects of oleuropein on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice, with diazepam as the standard drug. We also examined the possible involvement of opioidergic/nitrergic pathways in the probable effects of oleuropein. Intraperitoneal (i.p.) administration of different doses of oleuropein (10, 20 and 30 mg/kg) significantly increased the seizure threshold 60 min prior to induction of seizure, in a dose-dependent manner...
January 19, 2017: Journal of Natural Medicines
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
#16
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/28105513/pharmacokinetics-of-ginkgolides-a-b-and-k-after-single-and-multiple-intravenous-infusions-and-their-interactions-with-midazolam-in-healthy-chinese-male-subjects
#17
Feng Shao, Hongwen Zhang, Lijun Xie, Juan Chen, Sufeng Zhou, Jinsong Zhang, Jinru Lv, Weiwen Hao, Yunsu Ma, Yun Liu, Ning Ou, Wei Xiao
PURPOSE: Ginkgo terpene lactones meglumine injection (GMI) is a novel preparation of traditional Chinese medicine that contains ginkgolides A, B and K (GA, GB, GK, respectively) as its primary components. In this study we evaluated the safety, tolerability and pharmacokinetics of these three ginkgolides after single and multiple intravenous infusions of GMI. We also investigated the effect of GMI on cytochrome P450 3A4 (CYP3A4) in healthy Chinese volunteers. METHODS: In this open-label, placebo-controlled study 15 subjects were randomly assigned to receive GMI or matched placebo (4:1 ratio)...
January 20, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28104971/anti-inflammatory-and-anti-nociceptive-activities-of-stem-bark-extracts-and-fractions-of-carpolobia-lutea-polygalaceae
#18
Lucky Legbosi Nwidu, Blessing Airhihen, Augustine Ahmadu
BACKGROUND: In Niger Delta, ethnomedicine hydroalcoholic extract of Carpolobia lutea (CL) (Polygalaceae) is used to relieve inflammatory pains. OBJECTIVES: The purpose of this study is to evaluate the anti-inflammatory and antinociceptive effects of ethanolic stem extract (ESE) and to fractionate the ESE for the elucidation of bioactive molecules. MATERIALS AND METHODS: The antinociceptive effects for ESE were tested against two noxious stimuli; chemical (acetic acid-induced writhing and formalin-induced pain) and thermal (hot plate) stimuli...
December 2016: Journal of Basic and Clinical Pharmacy
https://www.readbyqxmd.com/read/28104300/challenges-and-opportunities-in-primary-cns-lymphoma-a-systematic-review
#19
REVIEW
Mariana N Kerbauy, Fabio Y Moraes, Benjamin H Lok, Jennifer Ma, Lucila N Kerbauy, Daniel E Spratt, Fabio P S Santos, Guilherme F Perini, Alejandro Berlin, Caroline Chung, Nelson Hamerschlak, Joachim Yahalom
BACKGROUND: Historically, high-dose methotrexate (HD-MTX) plus consolidation chemotherapy and/or whole brain radiotherapy (WBRT) has been the gold standard on Primary Central Nervous System Lymphoma (PCNSL) management. We sought to examine and summarize the data, on clinical trial (CT) setting, investigating multi-modality treatment to PCNSL. METHODS: We performed a systematic review of electronic databases (Medline, EMBASE, Cochrane Database and clinicaltrials...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28104252/novel-zebrafish-eae-model-a-quick-in-vivo-screen-for-multiple-sclerosis
#20
Pushkar Kulkarni, Swapna Yellanki, Raghavender Medishetti, Dharmarajan Sriram, Uday Saxena, Perumal Yogeeswari
INTRODUCTION: Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators...
January 2017: Multiple Sclerosis and related Disorders
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