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https://www.readbyqxmd.com/read/29156491/long-term-calcineurin-inhibitor-therapy-and-brain-function-in-patients-after-liver-transplantation
#1
Henning Pflugrad, Anna-Kristina Schrader, Anita Blanka Tryc, Xiaoqi Ding, Heinrich Lanfermann, Elmar Jäckel, Harald Schrem, Jan Beneke, Hannelore Barg-Hock, Jürgen Klempnauer, Karin Weissenborn
BACKGROUND AND AIMS: Calcineurin inhibitors (CNI) frequently induce neurological complications early after orthotopic liver transplantation (OLT). We hypothesize that long-term CNI therapy after OLT causes dose-dependent cognitive dysfunction and alteration of brain structure. METHODS: Eighty-five OLT patients (20 with CNI free, 35 with CNI low dose and 30 with standard dose CNI immunosuppression) underwent psychometric testing and cerebral magnetic resonance tomography about 10 years after OLT to assess brain function and structural brain alterations...
November 20, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29118206/social-origins-of-developmental-risk-for-mental-and-physical-illness
#2
Judy L Cameron, Kathie L Eagleson, Nathan A Fox, Takao K Hensch, Pat Levitt
Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29116375/uncoupling-n-acetylaspartate-from-brain-pathology-implications-for-canavan-disease-gene-therapy
#3
Georg von Jonquieres, Ziggy H T Spencer, Benjamin D Rowlands, Claudia B Klugmann, Andre Bongers, Anne E Harasta, Kristina E Parley, Jennie Cederholm, Orla Teahan, Russell Pickford, Fabien Delerue, Lars M Ittner, Dominik Fröhlich, Catriona A McLean, Anthony S Don, Miriam Schneider, Gary D Housley, Caroline D Rae, Matthias Klugmann
N-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease-a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation...
November 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29114910/n-acetylcysteine-attenuates-the-cuprizone-induced-behavioral-changes-and-oligodendrocyte-loss-in-male-c57bl-7-mice-via-its-anti-inflammation-actions
#4
Lin Zhang, Shuqin Xu, Qingjun Huang, Haiyun Xu
Previous animal studies have linked white matter damage to certain schizophrenia-like behaviors in cuprizone (CPZ)-exposed mouse. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and oligodendrocyte loss coexist in the brain of such mice. The aim of this study was to examine effects of the antioxidant N-acetylcysteine (NAC) on CPZ-induced behavioral changes and concurrent oligodendrocyte loss, oxidative stress, and neuroinflammation in these animals. Male C57BL/6 mice were given intraperitoneal saline or NAC at doses of 100, 200, and 400 mg/kg/day for 2 weeks; animals were fed a CPZ-containing diet (0...
November 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29073552/chemotherapy-induced-cognitive-impairments-white-matter-pathologies
#5
REVIEW
A Matsos, M Loomes, I Zhou, E Macmillan, I Sabel, E Rotziokos, W Beckwith, I N Johnston
Whilst chemotherapeutic agents show promising results in the amelioration of cancerous tumors, patients often experience cognitive disturbances associated with chemotherapy long after treatment has ceased. Research has suggested that the structural integrity of white matter fibres in the brain are susceptible to the harmful effects of chemotherapy. Post-chemotherapy, white matter tracts often display altered morphology with a reduction in glial cells such as oligodendrocytes. Demyelination, gliosis and leukoencephalopathy during or post chemotherapy is associated with changes in processing speed and IQ...
October 12, 2017: Cancer Treatment Reviews
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
#6
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 18F-fluoro-ethyl tyrosine PET...
November 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
#7
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
#8
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
#9
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
#10
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 (27-219 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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