Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Culture of neuroblastoma cells in a medium of low-thiamine concentration (6 nM) and in the presence of the transport inhibitor amprolium leads to the appearance of overt signs of necrosis; i.e., the chromatin condenses in dark patches, the oxygen consumption decreases, mitochondria are uncoupled, and their cristae are disorganized. Glutamate formed from glutamine is no longer oxidized and accumulates, suggesting that the thiamine diphosphate-dependent alpha-ketoglutarate dehydrogenase activity is impaired. When thiamine (10 microM) is added to the cells, the O2 consumption increases, respiratory control is restored, and normal cell and mitochondrial morphology is recovered within 1 h. Succinate, which is oxidized via the thiamine diphosphate-independent succinate dehydrogenase, is also able to restore a normal O2 consumption (with respiratory control) in digitonin-permeabilized thiamine-deficient cells. Our results therefore suggest that the slowing of the citric acid cycle is the main cause of the biochemical lesion induced by thiamine deficiency as observed in Wernicke's encephalopathy.
 ...
PMID:Thiamine deficiency--induced partial necrosis and mitochondrial uncoupling in neuroblastoma cells are rapidly reversed by addition of thiamine. 759 5

Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously.
...
PMID:Wernicke's encephalopathy in a child with high dose thiamine therapy. 2555 Jul 5

Children undergoing intense cancer treatment frequently require total parenteral nutrition (TPN). Rarely, vitamins are removed due to hypersensitivity to the carrier vehicle in the formulation. We present the case of a 5-year-old patient with stage 4, high-risk neuroblastoma who developed altered mental status, ataxia, and tachycardia during consolidative autologous stem cell transplantation. Skin findings and brain MRI were consistent with thiamine (vitamin B1) deficiency and Wernicke encephalopathy. Vitamin B1 administration rapidly reversed all skin and neurologic symptoms. This case highlights the importance of close monitoring of micronutrients in pediatric patients receiving prolonged courses of chemotherapy and stem cell transplantation.
 ...
PMID:Stem Cell Transplant-Associated Wernicke Encephalopathy in a Patient with High-Risk Neuroblastoma. 2617 46