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Drug induced peripheral neuropathy

Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Arthur Carvalho Silva, Rodolpho Campos Braga, Salomão Dória Jorge, José Alexandre Marzagão Barbuto, Carolina Horta Andrade, Adilson Kleber Ferreira
Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jewel L Podratz, Han Lee, Patrizia Knorr, Stephanie Koehler, Steven Forsythe, Kelsey Lambrecht, Suzette Arias, Kiley Schmidt, Gabrielle Steinhoff, Georgiy Yudintsev, Amy Yang, Eugenia Trushina, Anthony Windebank
Cisplatin is an effective chemotherapy drug that induces peripheral neuropathy in cancer patients. In rodent dorsal root ganglion neurons, cisplatin binds nuclear and mitochondrial DNA (mtDNA) inducing DNA damage and apoptosis. Platinum-mtDNA adducts inhibit mtDNA replication and transcription leading to mitochondrial degradation. Cisplatin also induces climbing deficiencies associated with neuronal apoptosis in adult Drosophila melanogaster. Here we used Drosophila larvae that express green fluorescent protein in the mitochondria of motor neurons to observe the effects of cisplatin on mitochondrial dynamics and function...
October 17, 2016: Neurobiology of Disease
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi, Anurag Kuhad
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain...
October 18, 2016: Inflammopharmacology
Brian H Cohen, Michael P Gaspar, Alan H Daniels, Edward Akelman, Patrick M Kane
Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms...
October 14, 2016: Journal of Hand Surgery
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
Hong Wei, Hai-Yun Wu, Zuyue Chen, Ai-Niu Ma, Xiao-Fang Mao, Teng-Fei Li, Xin-Yan Li, Yong-Xiang Wang, Antti Pertovaara
Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by d-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH)...
September 24, 2016: Pharmacology, Biochemistry, and Behavior
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
Giulia Donvito, Jenny L Wilkerson, M Imad Damaj, Aron H Lichtman
Chemotherapy-induced peripheral neuropathy (CIPN) represents a serious complication associated with anticancer drugs. Although there are no medications available that effectively prevent CIPN, many classes of drugs have been used to treat this condition, including anticonvulsants, serotonin and noradrenaline reuptake inhibitors, and opioids. However, these theraputic options yielded inconclusive results in CIPN clincal trials and produce assorted side effects with their prolonged use. Thus, there is an urgent need to develop efficacious and safe treatments for CIPN...
September 8, 2016: Journal of Pharmacology and Experimental Therapeutics
F Yavuz, U Guzelkucuk
Leflunomide is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. Leflunomide induced side effects are hepatotoxicity, immunosuppression, skin reactions, peripheral neuropathy, hypertension, diarrhea, interstitial lung disease, and rarely oral mucosal lesions. Here, we presented an unusual case of gingival overgrowth associated with the use of leflunomide, which improved after ceasing the drug.
April 2016: Acta Reumatológica Portuguesa
Ramón García-Sanz, Luis Antonio Corchete, Miguel Alcoceba, María Carmen Chillon, Cristina Jiménez, Isabel Prieto, María García-Álvarez, Noemi Puig, Immaculada Rapado, Santiago Barrio, Albert Oriol, María Jesús Blanchard, Javier de la Rubia, Rafael Martínez, Juan José Lahuerta, Marcos González Díaz, María Victoria Mateos, Jesús Fernando San Miguel, Joaquín Martínez-López, María Eugenia Sarasquete
Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide...
September 8, 2016: Hematological Oncology
Maria Apellániz-Ruiz, Héctor Tejero, Lucía Inglada-Pérez, Lara Sánchez-Barroso, Gerardo Gutiérrez-Gutiérrez, Isabel Calvo, Beatriz Castelo, Andrés Redondo, Jesus García-Donás, Nuria Romero-Laorden, Maria Sereno, María Merino, Maria Currás-Freixes, Cristina Montero-Conde, Veronika Mancikova, Elisabeth Åvall-Lundqvist, Henrik Green, Fatima Al-Shahrour, Alberto Cascon, Mercedes Robledo, Cristina Rodriguez-Antona
PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes. EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment...
August 31, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Deirdre R Pachman, Rui Qin, Drew Seisler, Ellen M Lavoie Smith, Suneetha Kaggal, Paul Novotny, Kathryn J Ruddy, Jacqueline M Lafky, Lauren E Ta, Andreas S Beutler, Nina D Wagner-Johnston, Nathan P Staff, Axel Grothey, Patrick M Dougherty, Guido Cavaletti, Charles L Loprinzi
PURPOSE: Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes. METHODS: Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3 weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12 months post-treatment...
August 18, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Dariusz Iżycki, Adam Andrzej Niezgoda, Maciej Kaźmierczak, Tomasz Piorunek, Natalia Iżycka, Bogusława Karaszewska, Ewa Nowak-Markwitz
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi-ties and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN...
2016: Ginekologia Polska
Ujjawal Roy, Ajay Panwar, Alak Pandit, Susanta Kumar Das, Bhushan Joshi
Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as "metronidazole induced encephalopathy"(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication...
June 2016: Journal of Clinical and Diagnostic Research: JCDR
Gokmen Umut Erdem, Mutlu Dogan, Nebi Serkan Demirci, Nurullah Zengin
Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular deoxyribonucleic acid (DNA) by leading covalent bifunctional DNA adducts with cellular DNA. Major side effects of oxaliplatin are neurotoxicity (peripheral neuropathy), myelosuppression with moderate thrombocytopenia and gastrointestinal toxicity (diarrhea). Thrombocytopenia might be related to myelosuppression and/or drug-induced immune thrombocytopenia (DIIT)...
April 2016: Journal of Cancer Research and Therapeutics
Jing-Dun Xie, Shao-Rui Chen, Hong Chen, Wei-An Zeng, Hui-Lin Pan
Painful peripheral neuropathy is a severe adverse effect of chemotherapeutic drugs such as paclitaxel (Taxol). The glutamate N-methyl-d-aspartate receptors (NMDARs) are critically involved in the synaptic plasticity associated with neuropathic pain. However, paclitaxel treatment does not alter the postsynaptic NMDAR activity of spinal dorsal horn neurons. In this study, we determined whether paclitaxel affects presynaptic NMDAR activity by recording excitatory postsynaptic currents (EPSCs) of dorsal horn neurons in spinal cord slices...
September 9, 2016: Journal of Biological Chemistry
Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang
The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines...
2016: American Journal of Cancer Research
Chiara Campo, Miguel Inacio Da Silva Filho, Niels Weinhold, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The introduction of proteasome inhibitors in the treatment of multiple myeloma (MM) patients has been a therapeutic success. Peripheral neuropathy (PNP) remains one of the most frequent side-effects experienced by patients who receive these novel agents. Recent investigations on the mechanisms of PNP in patients treated with bortezomib have suggested genetic susceptibility to neurotoxicity. We used data from a genome-wide association study conducted on 646 bortezomib-treated German MM patients to replicate the previously reported associations between single-nucleotide polymorphisms (SNPs) in candidate genes and PNP in MM patients, including 298 SNPs with a nominal significance (p value <0...
July 16, 2016: Neurochemical Research
Ayumu Matsuoka, Ayako Mitsuma, Osamu Maeda, Hiroaki Kajiyama, Hitoshi Kiyoi, Yasuhiro Kodera, Masato Nagino, Hidemi Goto, Yuichi Ando
Chemotherapy-induced peripheral neurotoxicity (CIPN) seriously impairs patients' quality of life cumulatively and dose-dependently. Because assessment of CIPN usually depends on patients' subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point-of-care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck(®) , NeuroMetrix Inc...
July 14, 2016: Cancer Science
Aniqa Tasnim, Zoe Rammelkamp, Amy B Slusher, Krystyna Wozniak, Barbara S Slusher, Mohamed H Farah
BACKGROUND: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol(®)), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degeneration of peripheral axons, whether they also cause degeneration of central nervous system axons is not clear...
2016: BMC Neuroscience
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