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https://www.readbyqxmd.com/read/29054380/toxicity-and-efficacy-of-re-irradiation-of-high-grade-glioma-in-a-phase-i-dose-and-volume-escalation-trial
#1
Søren Møller, Per Munck Af Rosenschöld, Junia Costa, Ian Law, Hans Skovgaard Poulsen, Svend Aage Engelholm, Silke Engelholm
INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy of PET and MRI guided re-irradiation of recurrent high-grade glioma (HGG) and to assess the impact of radiotherapy dose, fractionation and irradiated volume. MATERIAL AND METHODS: Patients with localized, recurrent HGG (grades III-IV) and no other treatment options were eligible for a prospective phase I trial. Gross tumor volumes for radiotherapy were defined using T1-contrast enhanced MRI and (18)F-fluoro-ethyl tyrosine PET...
October 17, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29047014/a-callosal-catastrophe-toxic-leukoencephalopathy-associated-with-thermogenic-weight-loss-supplement-use
#2
Zakraus K Mahdavi, Ram Narayan, Shraddha Mainali, Benjamin M Greenberg, Venkatesh Aiyagari, David L McDonagh
BACKGROUND: The use of weight loss drugs and dietary supplements is common, but safety profiles for these drugs are largely unknown. Reports of toxicity have been published, and the use of these agents should be considered in clinical differential diagnoses. METHODS: We report the case of a patient with toxic leukoencephalopathy and hyponatremia associated with oral consumption of a thermogenic dietary supplement and essential oils. RESULTS: A 30-year-old woman presented after 2 days of headache, blurred vision, photophobia, vomiting, and hand spasms...
October 18, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28910618/ran-translation-regulated-by-muscleblind-proteins-in-myotonic-dystrophy-type-2
#3
Tao Zu, John D Cleary, Yuanjing Liu, Monica Bañez-Coronel, Jodi L Bubenik, Fatma Ayhan, Tetsuo Ashizawa, Guangbin Xia, H Brent Clark, Anthony T Yachnis, Maurice S Swanson, Laura P W Ranum
Several microsatellite-expansion diseases are characterized by the accumulation of RNA foci and RAN proteins, raising the possibility of a mechanistic connection. We explored this question using myotonic dystrophy type 2, a multisystemic disease thought to be primarily caused by RNA gain-of-function effects. We demonstrate that the DM2 CCTG⋅CAGG expansion expresses sense and antisense tetrapeptide poly-(LPAC) and poly-(QAGR) RAN proteins, respectively. In DM2 autopsy brains, LPAC is found in neurons, astrocytes, and glia in gray matter, and antisense QAGR proteins accumulate within white matter...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28893007/mri-in-chemotherapy-induced-leukoencephalopathy-report-of-two-cases-and-radiologist-s-perspective
#4
Geetika Sindhwani, Manali Arora, Vishal Dhirenbhai Thakker, Abhinav Jain
Leukoencephalopathy is a progressive white matter disease primarily caused due to myelin damage by a variety of factors. Chemotherapy for oncological treatment is an uncommon but important cause of potentially reversible leukoencephalopathy. In current radiological setting, conventional and diffusion weighted MRI play a significant role in early and accurate detection of this entity. We are hereby presenting MRI evaluation of two cases of methotrexate and 5-fluorouracil induced toxic leukoencephalopathy.
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28875553/human-brain-imaging-of-nicotinic-acetylcholine-%C3%AE-4%C3%AE-2-receptors-using-18-f-nifene-selectivity-functional-activity-toxicity-aging-effects-gender-effects-and-extrathalamic-pathways
#5
Jogeshwar Mukherjee, Patrick J Lao, Tobey J Betthauser, Gurleen K Samra, Min-Liang Pan, Ishani H Patel, Christopher Liang, Raju Metherate, Bradley T Christian
Nicotinic acetylcholinergic receptors (nAChR's) have been implicated in several brain disorders, including addiction, Parkinson's disease, Alzheimer's disease and schizophrenia. Here we report in vitro selectivity and functional properties, toxicity in rats, in vivo evaluation in humans, and comparison across species of [(18) F]Nifene, a fast acting PET imaging agent for α4β2* nAChRs. Nifene had subnanomolar affinities for hα2β2 (0.34 nM), hα3β2 (0.80 nM) and hα4β2 (0.83 nM) nAChR but weaker (27 to 219 nM) for hβ4 nAChR subtypes and 169 nM for hα7 nAChR...
September 5, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28875534/postmortem-dti-reveals-altered-hippocampal-connectivity-in-wild-sea-lions-diagnosed-with-chronic-toxicosis-from-algal-exposure
#6
Peter F Cook, Gregory S Berns, Kathleen Colegrove, Shawn Johnson, Frances Gulland
Hundreds of wild California sea lions (Zalophus californianus) exposed to the algal neurotoxin domoic acid are treated in veterinary rehabilitation centers each year. Common chronic effects of toxic exposure in these animals are seizures and hippocampal damage, and they have been proposed as a natural animal model for human epilepsy. Humans with medial temporal lobe epilepsy present with white matter pathology in a number of tracts including the fornix and increased structural connectivity between the hippocampus and thalamus...
September 5, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28854700/comparison-of-spinocerebellar-ataxia-type-3-mouse-models-identifies-early-gain-of-function-cell-autonomous-transcriptional-changes-in-oligodendrocytes
#7
Biswarathan Ramani, Bharat Panwar, Lauren R Moore, Bo Wang, Rogerio Huang, Yuanfang Guan, Henry L Paulson
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene. This expansion leads to misfolding and aggregation of mutant ataxin-3 (ATXN3) and degeneration of select brain regions. A key unanswered question in SCA3 and other polyglutamine diseases is the extent to which neurodegeneration is mediated through gain-of-function versus loss-of-function. To address this question in SCA3, we performed transcriptional profiling on the brainstem, a highly vulnerable brain region in SCA3, in a series of mouse models with varying degrees of ATXN3 expression and aggregation...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28805273/neurotoxicosis-in-horses-associated-with-consumption-of-trema-micrantha
#8
M P Lorenzett, P R Pereira, D M Bassuino, G Konradt, W Panziera, M V Bianchi, F F Argenta, M E Hammerschmitt, R A Caprioli, C S L de Barros, S P Pavarini, D Driemeier
BACKGROUND: Trema micrantha is a tree widely distributed throughout the Americas. The tree produces highly palatable leaves that have been associated with natural poisoning in goats, sheep and horses, in which hepatic necrosis and hepatic encephalopathy have been observed. OBJECTIVES: This study describes malacia and haemorrhage in the central nervous system (CNS) due to T. micrantha consumption, with minimal to absent hepatic lesions. STUDY DESIGN: Retrospective case series...
August 14, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28714395/five-decades-of-cuprizone-an-updated-model-to-replicate-demyelinating-diseases
#9
Jose M Vega-Riquer, Gerardo Mendez-Victoriano, Raul A Morales-Luckie, Oscar Gonzalez-Perez
Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others comprise a group of demyelinating diseases characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter of the brain. To date, the etiology of these disorders is not well known and no effective treatments are currently available. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology of these diseases...
July 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28699400/regulatory-forum-opinion-piece-effective-sectioning-of-spinal-cord-during-regulatory-type-nonclinical-toxicity-studies
#10
Brad Bolon
Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord evaluation but do not specify a trimming scheme. The Society of Toxicologic Pathology (STP) "best practices" for nervous system sampling during nonclinical general toxicity studies recommend that spinal cord be assessed in both longitudinal/oblique and transverse sections. This article defines possible longitudinal/oblique orientations, describes their benefits and challenges, and provides an expert recommendation regarding suitable trimming planes...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28685296/methamphetamine-induced-toxic-leukoencephalopathy-clinical-radiological-and-autopsy-findings
#11
Jiao Mu, Meiyu Li, Ying Guo, Bin Lv, Mingjie Qiu, Hongmei Dong
Toxic leukoencephalopathy represents a process of structural alteration of the white matter. It is caused by substance abuse including drugs such as heroin, cocaine, toluene and ethanol. We reported the clinical, radiological and autopsy findings of a rare case of toxic leukoencephalopathy following chronic methamphetamine (MA) usage. A 34-year-old man with a 3-year history of MA abuse experienced progressive sluggish state, limb weakness, inability to stand and eating disorders, followed by rapid progression to coma and death...
July 6, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28670166/splenial-lesions-of-the-corpus-callosum-disease-spectrum-and-mri-findings
#12
Sung Eun Park, Dae Seob Choi, Hwa Seon Shin, Hye Jin Baek, Ho Cheol Choi, Ji Eun Kim, Hye Young Choi, Mi Jung Park
The corpus callosum (CC) is the largest white matter structure in the brain, consisting of more than 200-250 million axons that provide a large connection mainly between homologous cerebral cortical areas in mirror image sites. The posterior end of the CC is the thickest part, which is called the splenium. Various diseases including congenital to acquired lesions including congenital anomalies, traumatic lesions, ischemic diseases, tumors, metabolic, toxic, degenerative, and demyelinating diseases, can involve the splenium of the CC and their clinical symptoms and signs are also variable...
July 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28656068/toxins-in-brain-magnetic-resonance-mr-imaging-of-toxic-leukoencephalopathy-a-pictorial-essay
#13
REVIEW
Yogesh Kumar, Douglas Drumsta, Manisha Mangla, Nishant Gupta, Kusum Hooda, Jeevak Almast, Rajiv Mangla
Toxic leukoencephalopathy results from damage to the white matter caused by various toxins. It manifests itself as white matter signal abnormalities with or without the presence of restricted diffusion. These changes are often reversible if the insulting agent is removed early, with the exception of posthypoxic leukoencephalopathy that can manifest itself 1-2 weeks after the initial insult. However, many other potential causes of white matter signal abnormalities can mimic the changes of toxic leukoencephalopathy...
2017: Polish Journal of Radiology
https://www.readbyqxmd.com/read/28648949/welding-related-brain-and-functional-changes-in-welders-with-chronic-and-low-level-exposure
#14
Eun-Young Lee, Michael R Flynn, Mechelle M Lewis, Richard B Mailman, Xuemei Huang
Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e...
June 23, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28627273/nanoparticle-interactions-with-co-existing-contaminants-joint-toxicity-bioaccumulation-and-risk
#15
Rui Deng, Daohui Lin, Lizhong Zhu, Sanghamitra Majumdar, Jason C White, Jorge L Gardea-Torresdey, Baoshan Xing
With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants...
June 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28617152/impact-of-immunoablation-and-autologous-hematopoietic-stem-cell-transplantation-on-gray-and-white-matter-atrophy-in-multiple-sclerosis
#16
Hyunwoo Lee, Kunio Nakamura, Sridar Narayanan, Robert Brown, Jacqueline Chen, Harold L Atkins, Mark S Freedman, Douglas L Arnold
BACKGROUND: Immunoablation and autologous hematopoietic stem cell transplantation (IA/aHSCT) halts relapses, white matter (WM) lesion formation, and pathological whole-brain (WB) atrophy in multiple sclerosis (MS) patients. Whether the latter was due to effects on gray matter (GM) or WM warranted further exploration. OBJECTIVE: To model GM and WM volume changes after IA/aHSCT to further understand the effects seen on WB atrophy. METHODS: GM and WM volume changes were calculated from serial baseline and follow-up magnetic resonance imaging (MRI) ranging from 1...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28586011/microglia-activation-triggers-oligodendrocyte-precursor-cells-apoptosis-via-hsp60
#17
Yunhong Li, Rui Zhang, Xiaolin Hou, Yumei Zhang, Feijia Ding, Fan Li, Yao Yao, Yin Wang
Reactive microglia are present in lesions of myelin‑associated white matter disorders resulting in injuries to oligodendrocyte precursor cells (OPCs). Therefore, protection of OPCs from injury due to excessive activation of microglia is important in treating these diseases. Heat shock protein 60 (HSP60) has been demonstrated to be released extracellularly in the failing heart upon stress or injury. However, the role of HSP60 in the central nervous system and whether it participates in the toxic effects of microglia on OPCs remains unclear...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28543541/human-schwann-cells-exhibit-long-term-cell-survival-are-not-tumorigenic-and-promote-repair-when-transplanted-into-the-contused-spinal-cord
#18
Johana Bastidas, Gagani Athauda, Gabriela De La Cruz, Wai-Man Chan, Roozbeh Golshani, Yerko Berrocal, Martha Henao, Anil Lalwani, Chikato Mannoji, Mazen Assi, P Anthony Otero, Aisha Khan, Alexander E Marcillo, Michael Norenberg, Allan D Levi, Patrick M Wood, James D Guest, W Dalton Dietrich, Mary Bartlett Bunge, Damien D Pearse
The transplantation of rodent Schwann cells (SCs) provides anatomical and functional restitution in a variety of spinal cord injury (SCI) models, supporting the recent translation of SCs to phase 1 clinical trials for human SCI. Whereas human (Hu)SCs have been examined experimentally in a complete SCI transection paradigm, to date the reported behavior of SCs when transplanted after a clinically relevant contusive SCI has been restricted to the use of rodent SCs. Here, in a xenotransplant, contusive SCI paradigm, the survival, biodistribution, proliferation and tumorgenicity as well as host responses to HuSCs, cultured according to a protocol analogous to that developed for clinical application, were investigated...
August 2017: Glia
https://www.readbyqxmd.com/read/28534662/neuroprotection-of-brain-permeable-iron-chelator-vk-28-against-intracerebral-hemorrhage-in-mice
#19
Qian Li, Jieru Wan, Xi Lan, Xiaoning Han, Zhongyu Wang, Jian Wang
Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model...
September 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28506192/the-expanding-prominence-of-toxic-leukoencephalopathy
#20
Christopher M Filley, Brice V McConnell, C Alan Anderson
Toxic leukoencephalopathy (TL) is a disorder of brain white matter caused by exposure to leukotoxic agents. Magnetic resonance imaging (MRI) can readily identify this syndrome, and, together with diffusion tensor imaging, MRI continues to offer important insights into its nature. Since the first formal description of TL in 2001, many new leukotoxic disorders have been recognized, and the range of leukotoxins has expanded to include more therapeutic drugs, drugs of abuse, and environmental insults. While the understanding of pathophysiology remains incomplete, TL is increasingly common in clinical practice, and the potential long-term cognitive sequelae of toxic white matter injury merit attention...
May 16, 2017: Journal of Neuropsychiatry and Clinical Neurosciences
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