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Madison, WI, United States

Carlson N.G.,GRECC | Carlson N.G.,Neurovirology Laboratory 151B | Carlson N.G.,Research Service | Carlson N.G.,University of Utah | And 2 more authors.
Expert Opinion on Medical Diagnostics | Year: 2013

Introduction: Vitamin D has attracted a lot of attention in relation to multiple sclerosis (MS) and many other disorders; however, the evidence for a major role(s) for vitamin D in MS is compelling and multifactorial involving results from epidemiology, immunology, genetics, biochemistry and translational medicine. Areas covered: Multiple studies that illustrate that insufficient levels of vitamin D not only contribute to the risk of getting MS but may also worsen disease progression for MS patients are discussed. Genetic evidence also implicates vitamin D as being important in MS since individuals are at greater risk of getting MS if they harbor a mutation in a gene responsible for vitamin D synthesis (25-hydroxylase). Other modifiers of MS disease appear to interact with the vitamin D receptor. The Epstein-Barr virus (EBV) is a risk factor for MS and may in part worsen disease through the interactions between one of its gene products (EBNA-3) and the vitamin D receptor to attenuate vitamin D-regulated genes. Retrospective studies have shown that higher vitamin D levels are associated with a significant improvement of clinical and magnetic resonance imaging outcomes. Increasing clinical observations are also indicating adverse effects of low vitamin D in MS. Expert opinion: Mounting evidence from epidemiology, genetic, retrospective clinical studies and emerging basic science studies support a strong rationale for how vitamin D could be an important modifier of MS disease. Well-designed clinical trials are now ongoing and will provide further insight on how vitamin D supplementation may impact MS. © 2013 Informa UK, Ltd. Source

Xu G.,GRECC | Xu G.,University of Wisconsin - Madison | Rowley H.A.,University of Wisconsin - Madison | Wu G.,General Electric | And 7 more authors.
NMR in Biomedicine | Year: 2010

Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo-continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received 15O-water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross-modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/ white matter perfusion ratio (r=-0.62, p<0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional 15O-water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non-invasive in vivo examination of early pathophysiological changes in AD. Copyright © 2009 John Wiley & Sons, Ltd. Source

Erickson M.A.,GRECC | Erickson M.A.,University of Washington | Erickson M.A.,University of Pennsylvania | Banks W.A.,GRECC | Banks W.A.,University of Washington
Journal of Cerebral Blood Flow and Metabolism | Year: 2013

The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-β (Aβ) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Aβ pathology. © 2013 ISCBFM All rights reserved. Source

The examination of the contemporary legislative evolutions leads us to retain the implementation of a legislative device developing the obligation of care and the order of care in evolutionary transgressive contexts. In this evolution, the psychiatric examination sees its frame of intervention widening and its missions complicating, exceeding the question of the search for the institution of care, to become an object of functioning within a procedure. © 2014 Published by Elsevier Masson SAS. Source

Banks W.A.,GRECC | Banks W.A.,University of Washington | Morley J.E.,GRECC | Morley J.E.,Saint Louis University | And 4 more authors.
Peptides | Year: 2010

Insulin detemir has a different profile of action on the central nervous system (CNS) than human insulin. It has been hypothesized that this is caused by an altered ability of insulin detemir to cross the blood-brain barrier (BBB). Here, we measured the permeability of the BBB to insulin detemir. We labeled insulin detemir with radioactive iodine (I-Det) and examined its ability to cross the BBB of the mouse. Permeation was assessed after intravenous injection and by brain perfusion in the presence or absence of excess insulin detemir. The ability of insulin detemir to inhibit human insulin transport across the BBB was also assessed. I-Det did not cross the BBB either after intravenous injection or when studied by brain perfusion, a method which removes or reduces the influence of circulating proteins. Unlabeled detemir was about 10 times less potent than human insulin at inhibiting the transport of radioactive human insulin across the BBB. The altered CNS profile of insulin detemir may be caused by its poor access to CNS receptors and by a block of human insulin from crossing the BBB. Source

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