scholarly journals Genome-Wide Screen Identifies Drug-Induced Regulation of the Gene Giant Axonal Neuropathy (Gan) in a Mouse Model of Antiretroviral-Induced Painful Peripheral Neuropathy

2009 ◽  
Vol 11 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Susan G. Dorsey ◽  
Carmen C. Leitch ◽  
Cynthia L. Renn ◽  
Sherrie Lessans ◽  
Barbara A. Smith ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Mouse Model ◽  
Side Effect ◽  
Quantitative Polymerase Chain Reaction ◽  
Axonal Neuropathy ◽  
Protein Product ◽  
Hiv Treatment ◽  
Patient Comfort ◽  
Giant Axonal Neuropathy ◽  
Drug Induced

Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect. The mechanisms underlying the development of NRTI-induced neuropathy, however, remain unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an unbiased whole-genome microarray screen to identify molecular targets in the spinal dorsal horn, which is the location where integration of ascending sensory transmission and descending modulatory effects occur. Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy. Gan1 has not been previously linked to nerve pathologies in other populations. In this study, downregulation of the Gan1 gene and the gene protein product, gigaxonin, was validated via quantitative polymerase chain reaction ([qPCR] gene expression) and Western blot analyses (protein level). Our report is the first to suggest that Gan1 might be a novel molecular target in the development of NRTI-induced peripheral neuropathy with implications for new therapeutic approaches to preventing or reducing a significant side effect of HIV treatment.

scholarly journals Neuropathy in the setting of alcoholism-an entity less thought of

2020 ◽  
Vol 8 (12) ◽  
pp. 4518
Author(s):  
Shasthara Paneyala ◽  
Nemichandra S. C. ◽  
Harsha Sundaramurthy ◽  
Vimala Christina Colaco K.
Keyword(s):  
Peripheral Neuropathy ◽  
Side Effect ◽  
Axonal Neuropathy ◽  
Foot Drop ◽  
Sensory Loss ◽  
Adjunctive Treatment ◽  
Alcohol Dependency ◽  
Vitamin B ◽  
Motor Power ◽  
Vitamin B 12

Disulfiram is a commonly used adjunctive treatment in the management of alcohol dependency.  It has been noted that disulfiram can induce peripheral neuropathy, the mechanism of which has not been clearly determined. A 35-year-old patient, reformed alcoholic, on disulfiram presented with complaints of painful distal dysesthesias and foot drop. Clinical examination revealed bilateral foot drop without any objective sensory loss. Patient was evaluated for the same and routine blood investigations including vitamin B-12, inflammatory and virological markers were found to be normal. Nerve conductions studies revealed in excitable bilateral common peroneal and tibial nerves. Possibility of disulfiram induced peripheral neuropathy was thought of and drug was withdrawn. Patient was followed up and after two months improvement in motor power and reduction in paraesthesia’s was noted. Disulfiram is a commonly used drug, the uncommon side effect of which is distal predominant axonal neuropathy. This must be kept be kept in mind when evaluating a patient presenting with features of peripheral neuropathy, on a background of alcohol abuse.

scholarly journals Clinical Progression of Giant-Axonal Neuropathy over a Twelve Year Period

1981 ◽  
Vol 8 (4) ◽  
pp. 321-323 ◽  
Author(s):  
Joseph M. Dooley ◽  
Yasufumi Oshima ◽  
Laurence E. Becker ◽  
E. Gordon Murphy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Neuropathy ◽  
Clinical Course ◽  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy ◽  
Clinical Progression ◽  
Central Nervous System Dysfunction ◽  
Curly Hair

ABSTRACT:Giant-axonal neuropathy (GAN), a chronic peripheral neuropathy with associated Central Nervous System dysfunction and tight curly hair, is described in a 17-year-old girl. Biopsies of this girl’s muscle and nerve are characteristic of this condition. Her clinical course over a 12 year period characterizes a disease of a slowly progressive nature.

scholarly journals Metronidazole induced peripheral neuropathy

1970 ◽  
Vol 9 (2) ◽  
pp. 119-121 ◽  
Author(s):  
R Maskey ◽  
SK Sharma ◽  
KN Poudel
Keyword(s):  
Peripheral Neuropathy ◽  
Axonal Neuropathy ◽  
Drug Induced ◽  
Electrophysiologic Test ◽  
Hepatic Amebiasis

Metronidazole is a little known cause of drug-induced neuropathy.We report a patient who developed paraesthesia of both limbs after one month course of metronidazole. The electrophysiologic test confirmed a bilateral motor-axonal neuropathy. This neuropathy improved dramatically with cessation of the drug. Keywords: metronidazole; peripheral neuropathy; hepatic amebiasis DOI: http://dx.doi.org/10.3126/hren.v9i2.4986 Health Renaissance 2011: Vol.9 (No.2): 119-121

Giant Axonal Neuropathy in Siblings

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
A Naussed ◽  
I Heidrich ◽  
I Schreyer ◽  
HJ Mentzel ◽  
U Brandl
Keyword(s):  
Axonal Neuropathy ◽  
Giant Axonal Neuropathy

scholarly journals Drug Induced Encephalopathy in Patients with Chronic Kidney Disease: A Case Series

2018 ◽  
Vol 8 (2) ◽  
pp. 172-176
Author(s):  
Wasim Md Mohosin Ul Haque ◽  
Tabassum Samad ◽  
Muhammad Abdur Rahim ◽  
Shudhanshu Kumar Saha ◽  
Sarwar Iqbal
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Side Effect ◽  
Case Series ◽  
Special Group ◽  
Drug Induced ◽  
Reduced Dose

Drug induced encephalopathy is an established side effect of many drugs when used in a higher dose. Though we do not encounter this side effect frequently in our day to day practice, yet with renal impairment this is not uncommon. Even with a reduced dose many of these can precipitate encephalopathy in this special group of patients. We are presenting here a series of seven such cases of drug induced encephalopathy in patients with renal impairment.Birdem Med J 2018; 8(2): 172-176

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

2020 ◽  
pp. 109158182096151
Author(s):  
Jennifer C. Shing ◽  
Kai Schaefer ◽  
Shaun E. Grosskurth ◽  
Andy H. Vo ◽  
Tatiana Sharapova ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
Exploratory Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Small Rna Sequencing ◽  
Circulating Microrna ◽  
Testicular Toxicity ◽  
Potential Candidate ◽  
Drug Induced ◽  
Organ Systems

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.

scholarly journals Pustular Rash in Crohn’s Patient on Ustekinumab Raises Concern for Drug-Induced Paradoxical Psoriasis

2021 ◽  
pp. 662-666
Author(s):  
Mitra Barahimi ◽  
Scott Lee ◽  
Kindra Clark-Snustad
Keyword(s):  
Side Effect ◽  
De Novo ◽  
Pustular Psoriasis ◽  
Initial Weight ◽  
Drug Induced ◽  
Clinical Recurrence ◽  
Potential Side Effect ◽  
First Case ◽  
Tnf Antagonist ◽  
Subcorneal Pustular Dermatosis

We report the case of a 51-year-old male with Crohn’s disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.

Sign in / Sign up

Export Citation Format

Share Document