In vivo determination of multiexponential T2 relaxation in the brain of patients with multiple sclerosis

1991 ◽  
Vol 9 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Jean-Paul Armspach ◽  
Daniel Gounot ◽  
Lucien Rumbach ◽  
Jacques Chambron
Keyword(s):  
Multiple Sclerosis ◽  
T2 Relaxation ◽  
The Brain

Sensitive enzyme electrodes

1990 ◽  
Vol 333 (1628) ◽  
pp. 49-61 ◽  
Keyword(s):  
Packed Bed ◽  
Current Time ◽  
Enzyme Electrodes ◽  
Freely Moving ◽  
The Brain ◽  
Nanomolar Range ◽  
Inhibited Enzyme ◽  
Micromolar Range

Conventional enzyme electrodes are relatively insensitive devices capable of measuring analytes in the micromolar range. Inhibited enzyme electrodes work by measuring the inhibition of an enzyme turning over undersaturated conditions. This increased turnover gives greater sensitivity. The detection limits are controlled either by the thermodynamic amplitude or by the kinetic discrimination. Software has been developed to analyse the current time transient to produce concentrations of the inhibitor. Results for CN- and H 2 S are presented. The packed bed wall jet electrode is an electrode assembly that allows complete reaction of the substrate with the enzyme coupled to an efficient hydrodynamic régime for electrochemical detection. Results for the determination of acetylcholine are presented. The electrode can also be used in an immunoassay for the determination of human immunoglobulin in the nanomolar range. Finally results will be presented for in vivo changes in ascorbate in the brain of the freely moving rat as a result of tail pinch; changes on a timescale of half a second can be followed.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals An argument for broad use of high efficacy treatments in early multiple sclerosis

2019 ◽  
Vol 7 (1) ◽  
pp. e636 ◽  
Author(s):  
James M. Stankiewicz ◽  
Howard L. Weiner
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Approach ◽  
Disease Course ◽  
Long Term Outcomes ◽  
The Past ◽  
Recent Developments ◽  
The Brain

Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of the disease course is fraught, the amount of damage to the brain that MS causes is underappreciated, and its impact on patient function oftentimes is underestimated. These concerns, coupled with the recent availability of agents that allow a better therapeutic effect without compromising safety, lead us to believe that initiating higher efficacy treatments early is the best way to achieve the best possible long-term outcomes for people with MS.

scholarly journals Measurement of Bmax and Kd with the Glycine Transporter 1 Radiotracer 18F-MK6577 using a Novel Multi-Infusion Paradigm

2015 ◽  
Vol 35 (12) ◽  
pp. 2001-2009 ◽  
Author(s):  
Yan Xia ◽  
Ming-Qiang Zheng ◽  
Daniel Holden ◽  
Shu-fei Lin ◽  
Michael Kapinos ◽  
...  
Keyword(s):  
Rank Order ◽  
Target Concentration ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Positron Emission ◽  
Fitting Method ◽  
The Brain

Glycine is a co-agonist of glutamate at the NMDA receptor. Glycine transporter 1 (GlyT1) inhibitors are reported to be potential therapeutic agents for schizophrenia. 18F-MK6577 is a new positron emission tomography (PET) radiotracer useful for imaging brain GlyT1 and its occupancy in humans. We devised a novel multi-infusion paradigm of radiolabeled and unlabeled compound and an iterative linear/nonlinear alternating fitting method to allow for the determination of in vivo affinity ( Kd) and target concentration ( Bmax) images, constraining Kd to be uniform across the brain. This paradigm was tested with 18F-MK6577 in baboons. Voxel-based analysis produced high quality Bmax images and reliable Kd estimates, and also suggested that the nondisplaceable distribution volume ( VND) is not uniform throughout the brain. In vivo GlyT1 Kd was estimated to be 1.87 nmol/L for 18F-MK6577, and the rank order of GlyT1 distribution measured in the baboon brain was: high in the brainstem (133 nmol/L), medium in the cerebellum (83 nmol/L), and low in the cortex (30 nmol/L). These in vivo Kd and Bmax values agreed well with those determined in vitro, thus validating our novel multi-infusion approach.

Assessment of demyelination, edema, and gliosis byin vivo determination of T1 and T2 in the brain of patients with acute attack of multiple sclerosis

1989 ◽  
Vol 11 (3) ◽  
pp. 337-348 ◽  
Author(s):  
H. B. W. Larsson ◽  
J. Frederiksen ◽  
J. Petersen ◽  
A. Nordenbo ◽  
I. Zeeberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Acute Attack ◽  
T1 And T2 ◽  
The Brain

Determination of in vivo steady-state unbound drug concentration in the brain interstitial fluid by microdialysis

1992 ◽  
Vol 81 (2-3) ◽  
pp. 143-152 ◽  
Author(s):  
Terasaki Tetsuya ◽  
Deguchi Yoshiharu ◽  
Kasama Yuko ◽  
William M. Pardridge ◽  
Tsuji Akira
Keyword(s):  
Steady State ◽  
Drug Concentration ◽  
Interstitial Fluid ◽  
Brain Interstitial Fluid ◽  
The Brain
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