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Peripheral neurotoxicity

Matthew I Milowsky, Matthew D Galsky, Michael J Morris, Daniel J Crona, Daniel J George, Robert Dreicer, Kin Tse, Jesika Petruck, Iain J Webb, Neil H Bander, David M Nanus, Howard I Scher
BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m(2); 12 patients); every 2 weeks (120, 168, 236, and 330mg/m(2); 15 patients); every 3 weeks (330 and 426mg/m(2); 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m(2); 17 patients)...
October 17, 2016: Urologic Oncology
J M Parrott, L Redus, D Santana-Coelho, J Morales, X Gao, J C O'Connor
The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression...
October 18, 2016: Translational Psychiatry
M Andriamamonjy, J-B Delmotte, F Savinelli, H Beaussier, F Coudore
INTRODUCTION: Oxaliplatin is a platinum derivate widely used in cancer treatment but producing dose-limiting peripheral neurotoxicity. Acute neuropathy is characterized by a transient cold-induced distal allodynia whereas chronic neuropathy leads to sensory loss. In order to design a method for quantitative assessment of oxaliplatin-induced peripheral neuropathy, we developed a study that aims to characterize the most appropriate skin area of the hand to perform sensory tests. METHODS: We included patients treated during at least 6 months with oxaliplatin...
October 1, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
N Rajasekar, Chandishwar Nath, Kashif Hanif, Rakesh Shukla
Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test...
October 11, 2016: Molecular Neurobiology
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
October 5, 2016: Critical Reviews in Toxicology
A Hadar, E Milanesi, A Squassina, P Niola, C Chillotti, M Pasmanik-Chor, O Yaron, P Martásek, M Rehavi, D Weissglas-Volkov, N Shomron, I Gozes, D Gurwitz
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques...
October 4, 2016: Translational Psychiatry
Hiroshi Kuroda, Yoshiyuki Mukai, Shuhei Nishiyama, Takayuki Takeshita, Maki Tateyama, Atsushi Takeda, Masashi Aoki
Thallium intoxication was reported in cases with accidental ingestion, suicide attempt, and criminal adulteration. Reported cases were mostly one-time ingestion, therefore, the clinical course of divisional ingestion has not been fully known. Here, we report a case with two-step thallium intoxication manifesting as tardily accelerated neurologic deterioration. A 16-year-old adolescent was cryptically poisoned with thallium sulfate twice at an interval of 52days. After the first ingestion, neurologic symptoms including visual loss, myalgia, and weakness in legs developed about 40days after the development of acute gastrointestinal symptoms and alopecia...
September 28, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
W Huang, M Calvo, T Pheby, D L H Bennett, A S C Rice
HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours...
September 23, 2016: Pain
Tejaswi Kandula, Susanna B Park, Richard J Cohn, Arun V Krishnan, Michelle A Farrar
BACKGROUND: The dramatic increase in the number of childhood cancer survivors over the last 60years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches...
September 10, 2016: Cancer Treatment Reviews
Elham Memari, Mohammad-Ali Hosseinian, Ali Mirkheshti, Ali Arhami-Dolatabadi, Mojtaba Mirabotalebi, Mohsen Khandaghy, Yahya Daneshbod, Leila Alizadeh, Sadegh Shirian
Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0...
September 17, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Huaping Huang, Mei He, Lihua Liu, Lili Huang
AIM OF THIS STUDY: Chemotherapy-induced peripheral neuropathy (CIPN) is a major complication of cancer patients with chemotherapy. Although many interventions have been evaluated in previous studies, findings are controversial. The aim of this meta-analysis is to assess the efficacy of vitamin E supplementation in preventing CIPN. MATERIAL AND METHODS: The electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched from their inception to December 31, 2013 to identify relevant randomised controlled trials...
2016: Contemporary Oncology Współczesna Onkologia
Thiago Carrazoni, Marines de Avila Heberle, Ana Paula Artusi Perin, Ana Paula Zanatta, Polyana Veloso Rodrigues, Fabiola Duarte Machado Dos Santos, Carlos Gabriel Moreira de Almeida, Ricardo Vaz Breda, Douglas Silva Dos Santos, Paulo Marcos Pinto, Jaderson Costa da Costa, Celia Regina Carlini, Cháriston André Dal Belo
BACKGROUND: Ureases of Canavalia ensiformis are natural insecticides with a still elusive entomotoxic mode of action. We have investigated the mechanisms involved in the neurotoxicity induced by Jack Bean Urease (JBU) in Nauphoeta cinerea (Olivier). METHODS: To carry out this study we have employed biochemical and neurophysiological analysis of different cockroach organ systems. RESULTS AND CONCLUSIONS: The injection of the insects with JBU (0...
August 10, 2016: Toxicology
Allison M Bradbury, Jessica H Bagel, Xuntian Jiang, Gary P Swain, Maria L Prociuk, Caitlin A Fitzgerald, Patricia A O'Donnell, Kyle G Braund, Daniel S Ory, Charles H Vite
Globoid cell leukodystrophy (GLD), or Krabbe's disease, is a debilitating and always fatal pediatric neurodegenerative disease caused by a mutation in the gene encoding the hydrolytic enzyme galactosylceramidase (GALC). In the absence of GALC, progressive loss of myelin and accumulation of a neurotoxic substrate lead to incapacitating loss of motor and cognitive function and death, typically by 2 years of age. Currently, there is no cure. Recent convincing evidence of the therapeutic potential of combining gene and cell therapies in the murine model of GLD has accelerated the requirement for validated markers of disease to evaluate therapeutic efficacy...
November 2016: Journal of Neuroscience Research
Je-Seong Won, Avtar K Singh, Inderjit Singh
Krabbe's disease (KD; also called globoid cell leukodystrophy) is a genetic disorder involving demyelination of the central (CNS) and peripheral (PNS) nervous systems. The disease may be subdivided into three types, an infantile form, which is the most common and severe; a juvenile form; and a rare adult form. KD is an autosomal recessive disorder caused by a deficiency of galactocerebrosidase activity in lysosomes, leading to accumulation of galactoceramide and neurotoxic galactosylsphingosine (psychosine [PSY]) in macrophages (globoid cells) as well as neural cells, especially in oligodendrocytes and Schwann cells...
November 2016: Journal of Neuroscience Research
Shigeru Tsuyuki, Noriko Senda, Yookija Kanng, Ayane Yamaguchi, Hiroshi Yoshibayashi, Yuichiro Kikawa, Nobuyuki Katakami, Hironori Kato, Takashi Hashimoto, Toshitaka Okuno, Akira Yamauchi, Takashi Inamoto
PURPOSE: To investigate the efficacy of using surgical glove (SG) compression therapy to prevent nanoparticle albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Patients with primary and recurrent breast cancer who received 260 mg/m(2) of nab-PTX were eligible for this case-control study. Patients wore two SGs of the same size, i.e., one size smaller than the size that fit their dominant hand, for only 90 min. They did not wear two SGs on the non-dominant hand, which served as the control hand...
November 2016: Breast Cancer Research and Treatment
Dimitra Zagoura, David Canovas-Jorda, Francesca Pistollato, Susanne Bremer-Hoffmann, Anna Bal-Price
Human induced pluripotent stem cells (hiPSCs) are considered as a powerful tool for drug and chemical screening and development of new in vitro testing strategies in the field of toxicology, including neurotoxicity evaluation. These cells are able to expand and efficiently differentiate into different types of neuronal and glial cells as well as peripheral neurons. These human cells-based neuronal models serve as test systems for mechanistic studies on different pathways involved in neurotoxicity. One of the well-known mechanisms that are activated by chemically-induced oxidative stress is the Nrf2 signalling pathway...
September 8, 2016: Neurochemistry International
Yueh-Ling Hsieh, Li-Wei Chou, Shao-Fu Hong, Fei-Chi Chang, Szu-Wen Tseng, Chi-Chou Huang, Ching-Hsiang Yang, Chen-Chia Yang, Wei-Feng Chiu
BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited...
October 2016: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
Janet M Schloss, Maree Colosimo, Caroline Airey, Paul Masci, Anthony W Linnane, Luis Vitetta
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy. METHODS: A pilot, randomised, placebo-controlled trial was conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin or vincristine were invited to participate...
September 9, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Mark R Kelley, James H Wikel, Chunlu Guo, Karen E Pollok, Barbara J Bailey, Randy Wireman, Melissa L Fishel, Michael R Vasko
Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating side effect of a number of chemotherapeutic agents. There are currently no U.S. Food and Drug Administration-approved interventions or prevention strategies for CIPN. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. DNA damage in sensory neurons after chemotherapy correlates with symptoms of CIPN...
November 2016: Journal of Pharmacology and Experimental Therapeutics
Guy Madison, Michael A Woodley Of Menie, Justus Sänger
There are indications that simple reaction time might have slowed in Western populations, based on both cohort- and multi-study comparisons. A possible limitation of the latter method in particular is measurement error stemming from methods variance, which results from the fact that instruments and experimental conditions change over time and between studies. We therefore set out to measure the simple auditory reaction time (SRT) of 7,081 individuals (2,997 males and 4,084 females) born in Sweden 1959-1985 (subjects were aged between 27 and 54 years at time of measurement)...
2016: Frontiers in Human Neuroscience
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