Although prion propagation is well understood, the signaling pathways activated by neurotoxic forms of prion protein (PrP) and those able to mitigate pathological phenotypes remain largely unknown. Here, we identify src-2, a Fyn-related kinase, as a gene required for human PrP with an insertional mutation to be neurotoxic in Caenorhabditis elegans, and the longevity modulator sir-2.1/SIRT1, a s...

We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1-1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed ...

Cisplatin, carboplatin, and oxaliplatin anticancer drugs are commonly used to treat lung, colorectal, ovarian, breast, head and neck, and genitourinary cancers. However, the efficacy of platinum-based drugs is often compromised because of the substantial risk for severe toxicities, including neurotoxicity. Neurotoxicity can result in both acute and chronic debilitation. Moreover, colorectal can...

AIM The aim of the study was to compare two different neurotoxicity scales in grading chemotherapy-induced neurotoxicity. PATIENTS AND METHODS The study sample consisted of 114 cancer patients who started chemotherapy with vinca alcaloids, platinum derivatives or taxanes. Neurotoxicity was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) and oxaliplatin scales a...

To examine the role of Ca2+ in early neuronal death, we studied the impact of free intracellular calcium concentration ([Ca2+]i) on survivability in populations of cultured mouse spinal neurons. We asked whether early neurotoxicity was triggered by Ca2+ influx, whether elevated [Ca2+]i was a predictive indicator of impending neuronal death, and whether factors other than [Ca2+]i increases influ...

Behavioral end points are being used with greater frequency in neurotoxicology to detect and characterize the adverse effects of chemicals on the nervous system. Behavioral measures are particularly important for neurotoxicity risk assessment since many known neurotoxicants do not result in neuropathology. The chlorinated hydrocarbon class consists of a wide variety of chemicals including polyc...

Oxaliplatin use in palliative and adjuvant treatment of colon cancer is frequently limited by cumulative neurotoxicity, leading to reduced quality of life and decreased dose. The mechanism of this neurotoxicity is unclear, but may relate to neuronal voltage-gated sodium channels involving calcium chelation by a metabolite of the drug. Various preventative measures have been tested to reduce the...

Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is commonly associated with excitotoxicity, oxidative stress, and neuroinflammation. The pathological process of neurotoxicity induces neuronal death, interrupts synaptic plasticity in the brain, and is similar to that of diverse neurodegenerative diseases. Animal models of neurotoxicity have revealed that clinical sy...

INTRODUCTION C eftriaxone (CTRX) is a third-generation cephalosporin widely used to treat common infections such as pneumonia and urinary tract infections. The therapeutic dose is usually 1 to 2 g/d administered i.v. and can be increased up to 4 g/d for severe infections. Because CTRX is excreted via the biliary and the urine, patients with renal failure require no adjustment in dosage. However...

each, although toxicities were not directly attributed to the agent.2 In their letter, Chamberlain and Glantz comment on the neurologic syndromes we reported and question attribution to liposomal cytarabine. Our attributions were based on 15-year experience in nearly 500 adults with acute lymphoblastic leukemia without central nervous system (CNS) disease, treated with hyperCVAD (cyclophosphami...