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Peripheral neurotoxicity

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https://www.readbyqxmd.com/read/29439162/incidence-and-disease-burden-of-chemotherapy-induced-peripheral-neuropathy-in-a-population-based-cohort
#1
Arya Shah, E Matthew Hoffman, Michelle L Mauermann, Charles L Loprinzi, Anthony J Windebank, Christopher J Klein, Nathan P Staff
OBJECTIVE: To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. METHODS: Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for all subjects...
February 8, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29438899/elemental-mercury-neurotoxicity-and-clinical-recovery-of-function-a-review-of-findings-and-implications-for-occupational-health
#2
REVIEW
Edward J Calabrese, Ivo Iavicoli, Vittorio Calabrese, Deborah A Cory-Slechta, James Giordano
This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cases, the extent of such recoveries varied considerably by individual and endpoint. Factors accounting for the extensive inter-individual variation in toxicity and recovery were not specifically assessed such as age, gender, diet, environmental enrichment, chelation strategies and dose-rate...
February 9, 2018: Environmental Research
https://www.readbyqxmd.com/read/29438451/the-hard-road-to-data-interpretation-three-or-six-months-of-adjuvant-chemotherapy-for-patients-with-stage-iii-colon-cancer
#3
A Sobrero, A Grothey, T Iveson, R Labianca, T Yoshino, J Taieb, T Maughan, M Buyse, T Andre, J Meyerhardt, A F Shields, I Souglakos, J-Y Douillard, A Cervantes
Background: Six months of adjuvant oxaliplatin-based chemotherapy is standard for patients with stage III colon cancer following surgery. However, oxaliplatin is associated with peripheral neurotoxicity which worsens over treatment duration. Consequently, a shorter treatment duration, if equally effective would be extremely beneficial. A pooled analysis of data for 12,834 stage III colon cancer patients, from six randomised phase III trials of adjuvant therapy, the IDEA study, was performed and the results presented at the ASCO Annual Meeting 2017...
February 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29433564/high-dose-thiotepa-related-neurotoxicity-and-the-role-of-tramadol-in-children
#4
Christophe Maritaz, Francois Lemare, Agnes Laplanche, Sylvie Demirdjian, Dominique Valteau-Couanet, Christelle Dufour
BACKGROUND: Serious neurological adverse events (NAE) have occurred during treatment with high-dose thiotepa regimens of children with high-risk solid tumours. The objective was to assess the incidence of NAE related to high-dose thiotepa and to identify potential contributing factors that could exacerbate the occurrence of this neurotoxicity. METHODS: From May 1987 to March 2011, children with solid tumours treated with high-dose thiotepa were retrospectively identified...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29427706/in-vitro-assessment-of-chemotherapy-induced-neuronal-toxicity
#5
Chelsea Snyder, Lanlan Yu, Tin Ngo, Daniel Sheinson, Yuda Zhu, Min Tseng, Dinah Misner, Karin Staflin
Neurotoxicity is a major concern during drug development, and together with liver and cardio-toxicity, it is one of the main causes of clinical drug attrition. Current pre-clinical models may not sufficiently identify and predict the risk for central or peripheral nervous system toxicity. One such example is clinically dose-limiting neuropathic effects after the administration of chemotherapeutic agents. Thus, the need to establish novel in vitro tools to evaluate the risk of neurotoxicities, such as neuropathy, remains unmet in drug discovery...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29423527/a-high-throughput-approach-to-identify-specific-neurotoxicants-developmental-toxicants-in-human-neuronal-cell-function-assays
#6
Johannes Delp, Simon Gutbier, Stefanie Klima, Lisa Hoelting, Kevin Pinto-Gil, Jui-Hua Hsieh, Michael Aichem, Karsten Klein, Falk Schreiber, Raymond R Tice, Manuel Pastor, Mamta Behl, Marcel Leist
The (developmental) neurotoxicity hazard is still unknown for most chemicals. Establishing a test battery covering most of the relevant adverse outcome pathways may close this gap, without requiring a huge animal experimentation program. Ideally, each of the assays would cover multiple mechanisms of toxicity. One candidate test is the human LUHMES cell-based NeuriTox test. To evaluate its readiness for larger-scale testing, a proof of concept library assembled by the U.S. National Toxicology Program (NTP) was screened...
January 21, 2018: ALTEX
https://www.readbyqxmd.com/read/29414872/suramin-induced-neurotoxicity-preclinical-models-and-neuroprotective-strategies
#7
David von der Ahe, Petra Huehnchen, Mustafa Balkaya, Sarah Peruzzaro, Matthias Endres, Wolfgang Boehmerle
Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca2+) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy...
February 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29407791/studies-on-the-interaction-of-bde-47-and-bde-209-with-acetylcholinesterase-ache-based-on-the-neurotoxicity-through-fluorescence-uv-vis-spectra-and-molecular-docking
#8
Shutao Wang, Chuan Wu, Zhisheng Liu, Hong You
The neurotoxicity of polybrominated diphenyl ethers (PBDEs) has been of concern. Acetylcholinesterase (AChE) is a critical enzyme in the central and peripheral nervous system related to neurotoxicity. The interaction between BDE-47, BDE-209, and AChE was investigated through fluorescence and UV-vis spectra combined with molecular docking. Both BDE-47 and BDE-209 bound with AChE and changed the microenvironment of some amino acid residues, resulting in a change of AChE conformation. Hydrophobic interaction is the main binding force between BDE-47, BDE-209, and AChE, and electrostatic interaction exists according to the thermodynamic parameters of the interaction between them...
February 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29390421/comprehensive-evaluation-of-clinical-efficacy-and-safety-of-celecoxib-combined-with-chemotherapy-in-management-of-gastric-cancer
#9
Qinghong Guo, Xiaojun Liu, Linzhi Lu, Hao Yuan, Yuping Wang, Zhaofeng Chen, Rui Ji, Yongning Zhou
BACKGROUND: To evaluate the clinical efficacy and safety of celecoxib combined with chemotherapy in the treatment of gastric cancer. METHODS: In total, 240 gastric cancer patients undergoing radical gastrectomy followed by adjuvant chemotherapy were randomly assigned into 2 groups. In the experimental group (n = 120), patients were administered with celecoxib-based chemotherapy, and chemotherapy alone was performed in the control group. Disease-free survival (DFS) and progression-free survival (PFS) were considered as the primary efficacy parameters, and objective response rate (ORR), overall survival (OS), quality of life (QOL), and safety as the secondary efficacy parameters...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29377255/agmatine-co-treatment-attenuates-allodynia-and-structural-abnormalities-in-cisplatin-induced-neuropathy-in-rats
#10
Basak Donertas, Cigdem Cengelli Unel, Sule Aydin, Emel Ulupinar, Orhan Ozatik, Bilgin Kaygisiz, Engin Yildirim, Kevser Erol
Cisplatin is a widely-used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity...
January 29, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29361042/two-year-trends-of-taxane-induced-neuropathy-in-women-enrolled-in-a-randomized-trial-of-acetyl-l-carnitine-swog-s0715
#11
Dawn L Hershman, Joseph M Unger, Katherine D Crew, Cathee Till, Heather Greenlee, Lori M Minasian, Carol M Moinpour, Danika L Lew, Louis Fehrenbacher, James L Wade, Siu-Fun Wong, Michael J Fisch, N Lynn Henry, Kathy S Albain
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. Methods: S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer...
January 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29360534/immune-effects-of-the-neurotoxins-ciguatoxins-and-brevetoxins
#12
Ophelie Pierre, Laurent Misery, Matthieu Talagas, Raphaele Le Garrec
Ciguatoxins (CTXs) and brevetoxins (PbTxs) are phycotoxins that can accumulate along the marine food chain and thus cause seafood poisoning in humans, namely "ciguatera fish poisoning" (CFP) and "neurotoxic shellfish poisoning" (NSP), respectively. CFP is characterized by early gastrointestinal symptoms and typical sensory disorders (paraesthesia, pain, pruritus and cold dysaesthesia), which can persist several weeks and, in some cases, several months or years. NSP is considered a mild form of CFP with similar but less severe symptoms...
January 19, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29352205/2-5-hexanedione-induces-dopaminergic-neurodegeneration-through-integrin-%C3%AE-m%C3%AE-2-nadph-oxidase-axis-mediated-microglial-activation
#13
Cong Zhang, Liyan Hou, Jie Yang, Yuning Che, Fuqiang Sun, Huihua Li, Qingshan Wang
Recent study demonstrated that chronic exposure to solvents increases the risk of Parkinson's disease (PD), the second most common neurodegenerative disorder characterized by progressive dopaminergic neurodegeneration in the substantia nigra (SN). n-Hexane, a widely used organic solvent, displays central-peripheral neurotoxicity, which is mainly mediated by its active metabolite, 2,5-hexanedione (HD). However, whether HD exposure contributes to PD remains unclear. In this study, we found that rats exposed to HD displayed progressive dopaminergic neurodegeneration in the nigrostriatal system...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#14
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29337310/oatp1b2-deficiency-protects-against-paclitaxel-induced-neurotoxicity
#15
Alix F Leblanc, Jason A Sprowl, Paola Alberti, Alessia Chiorazzi, W David Arnold, Alice A Gibson, Kristen W Hong, Marissa S Pioso, Mingqing Chen, Kevin M Huang, Vamsi Chodisetty, Olivia Costa, Tatiana Florea, Peter de Bruijn, Ron H Mathijssen, Raquel E Reinbolt, Maryam B Lustberg, Lara E Sucheston-Campbell, Guido Cavaletti, Alex Sparreboom, Shuiying Hu
Paclitaxel is among the most widely used anticancer drugs and is known to cause a dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain unknown. Here, we identified the murine solute carrier organic anion-transporting polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity. Additionally, using established tests to assess acute and chronic paclitaxel-induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29336266/design-synthesis-evaluation-and-computational-studies-of-nipecotic-acid-acetonaphthone-hybrids-as-potential-antiepileptic-agents
#16
Ankit Seth, Piyoosh A Sharma, Avanish Tripathi, Priyanka K Choubey, Pavan Srivastava, Prabhash N Tripathi, Sushant Kumar Shrivastava
BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial γ- aminobutyric acid (GABA) uptake in vitro. However nipecotic acid does not readily cross the blood-brain barrier (BBB) following peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series of substituted acetonaphthones tethered nipecotic acid derivatives were designed and synthesized with an aim to improve the lipophilicity and the blood-brain barrier (BBB) permeation...
January 15, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29319659/residual-neurological-symptoms-after-peripheral-nerve-blocks-for-pediatric-knee-surgery
#17
Robert J Tamai, Brian T Sullivan, Rushyuan J Lee
BACKGROUND: Peripheral nerve blocks (PNBs) provide excellent pain control and reduce the need for systemic analgesics in orthopaedic surgery. PNBs rarely cause complications; however, a few studies of adults have reported neurological complications during the early postoperative period. We investigated complications associated with the use of PNBs during pediatric knee surgery. METHODS: We reviewed the medical records of all 121 children (aged ≤18 y) who underwent knee surgery by 1 orthopaedic surgeon between October 2014 and September 2016...
January 9, 2018: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/29316888/the-preventive-effect-of-sensorimotor-and-vibration-exercises-on-the-onset-of-oxaliplatin-or-vinca-alkaloid-induced-peripheral-neuropathies-stop
#18
Fiona Streckmann, Maryam Balke, Helmar C Lehmann, Vanessa Rustler, Christina Koliamitra, Thomas Elter, Michael Hallek, Michael Leitzmann, Tilman Steinmetz, Petra Heinen, Freerk T Baumann, Wilhelm Bloch
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait...
January 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29282807/blocking-of-cytokines-signalling-attenuates-evoked-and-spontaneous-neuropathic-pain-behaviours-in-the-paclitaxel-rat-model-of-chemotherapy-induced-neuropathy
#19
S Al-Mazidi, M Alotaibi, T Nedjadi, A Chaudhary, M Alzoghaibi, L Djouhri
BACKGROUND: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious dose-limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural-immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP...
December 27, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29282364/mir-pharmacogenetics-of-vincristine-and-peripheral-neurotoxicity-in-childhood-b-cell-acute-lymphoblastic-leukemia
#20
Ángela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Nagore García de Andoin, Borja Santos, Ana Sastre, Aizpea Echebarria-Barona, Itziar Astigarraga, Aurora Navajas, Africa Garcia-Orad
Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function...
December 27, 2017: Pharmacogenomics Journal
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