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Peripheral neurotoxicity

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https://www.readbyqxmd.com/read/29034113/low-neurotoxicity-of-onx-0914-supports-the-idea-of-specific-immunoproteasome-inhibition-as-a-side-effect-limiting-therapeutic-strategy
#1
Laura von Brzezinski, Paula Säring, Peter Landgraf, Clemens Cammann, Ulrike Seifert, Daniela C Dieterich
Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific inhibitor of the β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively the proteasome subtypes mainly expressed in immune cells including B lymphocytes as the origin of multiple myeloma...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/29030217/impact-of-peripheral-immune-status-on-central-molecular-responses-to-facial-nerve-axotomy
#2
D O Setter, E M Runge, N D Schartz, F M Kennedy, B L Brown, K P McMillan, W M Miller, K M Shah, M M Haulcomb, V M Sanders, K J Jones
When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2(-/-)) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2(-/-) mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2(-/-) mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA...
October 10, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29020118/susceptibility-of-different-mouse-strains-to-oxaliplatin-peripheral-neurotoxicity-phenotypic-and-genotypic-insights
#3
Paola Marmiroli, Beatrice Riva, Eleonora Pozzi, Elisa Ballarini, Dmitry Lim, Alessia Chiorazzi, Cristina Meregalli, Carla Distasi, Cynthia L Renn, Sara Semperboni, Lavinia Morosi, Federico A Ruffinatti, Massimo Zucchetti, Susan G Dorsey, Guido Cavaletti, Armando Genazzani, Valentina A Carozzi
Peripheral neurotoxicity is one of the most distressing side effects of oxaliplatin therapy for cancer. Indeed, most patients that received oxaliplatin experience acute and/or chronic severe sensory peripheral neuropathy. However, despite similar co-morbidities, cancer stage, demographics and treatment schedule, patients develop oxaliplatin-induced peripheral neurotoxicity with remarkably different severity. This suggests individual genetic variability, which might be used to glean the mechanistic insights into oxaliplatin neurotoxicity...
2017: PloS One
https://www.readbyqxmd.com/read/29018286/complement-protein-c3-suppresses-axon-growth-and-promotes-neuron-loss
#4
Sheri L Peterson, Hal X Nguyen, Oscar A Mendez, Aileen J Anderson
The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3(-/-) mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3(+/+) mice...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28961308/nelarabine-induced-peripheral-and-central-neurotoxicity-can-sequential-mri-brain-imaging-help-to-define-its-natural-history
#5
Karl Ewins, Andrea Malone, Ethna Phelan, David Webb, J C McHugh, Owen Smith
A 14-year-old boy with relapsed T cell acute lymphoblastic leukaemia received reinduction chemotherapy that included nelarabine, a purine nucleoside analogue known to cause dose-dependent neurotoxicity. Although he achieved aminimal residual disease negative remission after two cycles of chemotherapy he also developed severe, progressive peripheral and central neurotoxicities. Loss of grey-white differentiation was seen on a T2-weighted magnetic resonance imaging brain scan. This unusual clinical picture and previously unreported radiological findings are thought to be due to nelarabine toxicity...
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28887203/clinical-relevance-of-metronidazole-and-peripheral-neuropathy-a-systematic-review-of-the-literature
#6
REVIEW
Tiffany A Goolsby, Bernadette Jakeman, Robert P Gaynes
The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources...
September 5, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28875469/a-panel-of-autoantibodies-against-neural-proteins-as-peripheral-biomarker-for-pesticide-induced-neurotoxicity
#7
Heba Allah Abd El Rahman, Mohamed Salama, Seham A Gad El-Hak, Mona A El-Harouny, Passent ElKafrawy, Mohamed B Abou-Donia
In the present study, we screened the sera of subjects chronically exposed to mixtures of pesticides (composed mainly of organophosphorus compounds (OPs) and others) and developed neurological symptoms for the presence of autoantibodies against cytoskeletal neural proteins. OPs have a well-characterized clinical profile resulting from acute cholinergic crisis. However, some of these compounds cause neuronal degeneration and demyelination known as organophosphorus compound-induced delayed neurotoxicity (OPIDN) and/or organophosphorus compound-induced chronic neurotoxicity (OPICN)...
September 5, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28865725/aluminum-exposure-for-60days-at-an-equivalent-human-dietary-level-promotes-peripheral-dysfunction-in-rats
#8
Caroline Silveira Martinez, Gema Vera, José Antonio Uranga Ocio, Franck Maciel Peçanha, Dalton Valentim Vassallo, Marta Miguel, Giulia Alessandra Wiggers
Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group - Low level - rats were subdivided and treated for 60days: a) Control - received ultrapure water; b) AlCl3 - received Al at 8.3mg/kg body weight (bw) for 60days; and 2) Second group - High level - rats were subdivided and treated for 42days: C) Control - received ultrapure water through oral gavage; d) AlCl3 - received Al at 100mg/kg bw for 42days...
August 25, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28861848/update-of-hiv-associated-sensory-neuropathies
#9
REVIEW
Angela Aziz-Donnelly, Taylor B Harrison
PURPOSE OF REVIEW: HIV-sensory neuropathy (HIV-SN) remains a common complication of HIV infection and may be associated with significant morbidity due to neuropathic pain. The overall purpose of this review is to discuss trends in the changing epidemiology in HIV-SN, new data regarding the pathophysiology of the condition, and discuss approaches to management. RECENT FINDINGS: While HIV-SN has been historically considered the most common neurological complication of HIV infection, improved accessibility to effective combination antiretroviral therapy (cART), use of less neurotoxic antiretroviral medication regimens, and trends towards earlier introduction of treatment have impacted the condition: overall incident HIV-SN is likely decreased compared to prior rates and patients afflicted by HIV-SN may more frequently have asymptomatic or subclinical disease...
August 31, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28843493/utilization-of-ipsc-derived-human-neurons-for-high-throughput-drug-induced-peripheral-neuropathy-screening
#10
Payal Rana, Gregory Luerman, Dietmar Hess, Elizabeth Rubitski, Karissa Adkins, Christopher Somps
As the number of cancer survivors continues to grow, awareness of long-term toxicities and impact on quality of life after chemotherapy treatment in cancer survivors has intensified. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of modern chemotherapy. Animal models are used to study peripheral neuropathy and predict human risk; however, such models are labor-intensive and limited translatability between species has become a major challenge. Moreover, the mechanisms underlying CIPN have not been precisely determined and few human neuronal models to study CIPN exist...
December 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28841420/a-macrophage-response-to-mycobacterium-leprae-phenolic-glycolipid-initiates-nerve-damage-in-leprosy
#11
Cressida A Madigan, C J Cambier, Kindra M Kelly-Scumpia, Philip O Scumpia, Tan-Yun Cheng, Joseph Zailaa, Barry R Bloom, D Branch Moody, Stephen T Smale, Alvaro Sagasti, Robert L Modlin, Lalita Ramakrishnan
Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28835396/human-dorsal-root-ganglion-in-vivo-morphometry-and-perfusion-in-fabry-painful-neuropathy
#12
Tim Godel, Philipp Bäumer, Mirko Pham, Anja Köhn, Nicole Muschol, Moritz Kronlage, Jennifer Kollmer, Sabine Heiland, Martin Bendszus, Victor-Felix Mautner
OBJECTIVE: To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy. METHODS: In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls...
September 19, 2017: Neurology
https://www.readbyqxmd.com/read/28820525/the-content-validity-of-a-chemotherapy-induced-peripheral-neuropathy-patient-reported-outcome-measure
#13
Ellen M Lavoie Smith, Rylie Haupt, James P Kelly, Deborah Lee, Grace Kanzawa-Lee, Robert Knoerl, Celia Bridges, Paola Alberti, Nusara Prasertsri, Clare Donohoe
PURPOSE/OBJECTIVES: To test the content validity of a 16-item version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20). 
. RESEARCH APPROACH: Cross-sectional, prospective, qualitative design. 
. SETTING: Six outpatient oncology clinics within the University of Michigan Health System's comprehensive cancer center in Ann Arbor. 
...
September 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28819738/high-dose-8-capsaicin-patch-in-treatment-of-chemotherapy-induced-peripheral-neuropathy-single-center-experience
#14
Iwona Filipczak-Bryniarska, Roger M Krzyzewski, Jakub Kucharz, Anna Michalowska-Kaczmarczyk, Justyna Kleja, Jarosław Woron, Katarzyna Strzepek, Lucyna Kazior, Jerzy Wordliczek, Tomasz Grodzicki, Krzysztof Krzemieniecki
High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded...
August 17, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28797868/neuropathic-pain-and-nerve-growth-factor-in-chemotherapy-induced-peripheral-neuropathy-prospective-clinical-pathological-study
#15
R Velasco, X Navarro, M Gil-Gil, M Herrando-Grabulosa, A Calls, J Bruna
CONTEXT: Neuropathic pain can be present in patients developing chemotherapy-induced peripheral neuropathy (CIPN). Nerve growth factor (NGF) is trophic to small sensory fibers and regulates nociception. OBJECTIVES: We investigated the changes in serum NGF and intraepidermal nerve fiber density (IENFD) in skin biopsies of cancer patients receiving neurotoxic chemotherapy in a single-center prospective observational study. METHODS: Patients were evaluated before and after chemotherapy administration...
August 7, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28795412/severe-neurological-disorders-and-refractory-aspergillosis-in-an-adolescent-treated-by-vincristine-and-voriconazole
#16
Y Bennis, S Bodeau, A Lutun, A Gourmel, C Solas, S Quaranta, N Guillaume, T Chouaki, A-S Lemaire-Hurtel, K Masmoudi
WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains...
August 10, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28790893/brain-and-peripheral-atypical-inflammatory-mediators-potentiate-neuroinflammation-and-neurodegeneration
#17
REVIEW
Duraisamy Kempuraj, Ramasamy Thangavel, Govindhasamy P Selvakumar, Smita Zaheer, Mohammad E Ahmed, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Prashant A Natteru, Shankar Iyer, Asgar Zaheer
Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28779867/neurological-complications-of-childhood-cancer
#18
Lauren Weaver, Ayman Samkari
Though the treatment of pediatric cancers has come a long way, acute and chronic effects of cancer are still affecting the life of many children. These effects may be caused not only by the malignancy itself but also by the interventions used for the purpose of treatment. This article focuses primarily on the indirect effects of pediatric cancers and their treatment on the central and peripheral nervous system. Chemotherapy, radiation, and stem cell transplantation cause an immune-compromised state and place the patient at risk of infection, the leading cause of mortality in pediatric cancer...
February 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28777427/paclitaxel-oxaliplatin-5-fluorouracil-and-leucovorin-combination-chemotherapy-in-patients-with-recurrent-or-metastatic-gastric-cancer
#19
Yan-Qin Lan, Ri-Ping Wu, Xiao-Bing Huang, Xin-Li Wang, Dong-Ta Zhong, Chuan-Yong Huang, Jin-Tian Song
PURPOSE: This study evaluated the efficacy and toxicity of combination chemotherapy with paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin (POFL) in patients with recurrent or metastatic gastric cancer. METHODS: One hundred and thirty-eight patients with histologically confirmed recurrent or metastatic gastric adenocarcinoma were treated with the POFL regimen: paclitaxel at a dose of 135 mg/m2 as a 3-hour intravenous infusion on day 1, oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 as an intravenous infusion over 2 hours on day 1, followed by 5-fluorouracil 2,400 mg/m2 as an infusion over a 46-hour period on 3 consecutive days, in a 2-week cycle...
July 27, 2017: Tumori
https://www.readbyqxmd.com/read/28771662/neurotoxic-side-effects-in-children-with-refractory-or-relapsed-t-cell-malignancies-treated-with-nelarabine-based-therapy
#20
MULTICENTER STUDY
Michaela Kuhlen, Kirsten Bleckmann, Anja Möricke, Martin Schrappe, Simon Vieth, Gabriele Escherich, Annika Bronsema, Annika Vonalt, Manon Queudeville, C Michel Zwaan, Martin Ebinger, Klaus-Michael Debatin, Thomas Klingebiel, Ewa Koscielniak, Claudia Rossig, Birgit Burkhardt, Reinhard Kolb, Cornelia Eckert, Arndt Borkhardt, Arend von Stackelberg, Christiane Chen-Santel
The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1-2 cycles of Ara-G...
October 2017: British Journal of Haematology
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