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 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.

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

scholarly journals Orexin A suppresses in vivo GH secretion

2004 ◽  
pp. 731-736 ◽  
Author(s):  
LM Seoane ◽  
SA Tovar ◽  
D Perez ◽  
F Mallo ◽  
M Lopez ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Area Under The Curve ◽  
Sleep Regulation ◽  
Gh Secretion ◽  
Neuroendocrine Function ◽  
Freely Moving Rats ◽  
Freely Moving ◽  
The Brain

BACKGROUND/AIMS: Orexins (OXs) are a newly described family of hypothalamic neuropeptides. Based on the distribution of OX neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrine function. GH secretion is markedly influenced by nutritional status and body weight. To investigate the role OX-A plays in the neuroregulation of GH secretion we have studied its effect on spontaneous GH secretion as well as GH responses to GHRH and ghrelin in freely moving rats. Finally, we also assessed the effect of OX-A on in vitro GH secretion. METHODS: We administered OX-A (10 microg, i.c.v.) or vehicle (10 microl, i.c.v.) to freely moving rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. RESULTS: Administration of OX-A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (means+/-s.e.m. 4.2+/-1.7 ng/ml vs 9.4+/-2.2 ng/ml; P<0.05), mean GH amplitude (3.6+/-0.5 ng/ml vs 20.8+/-5.6 ng/ml; P<0.01) and area under the curve (848+/-379 ng/ml per 4 h vs 1957+/-458 ng/ml per 4 h; P<0.05). In contrast, OX-A failed to modify in vivo GH responses to GHRH (10 microg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 microg/kg, i.v.) (mean peak GH levels: 331+/-71 ng/ml, vehicle, vs 43+/-11 ng/ml in OX-A-treated rats; P<0.01). Finally, OX-A infusion (10(-7), 10(-8) or 10(-9) M) failed to modify in vitro basal GH secretion or GH responses to GHRH, ghrelin and KCl. CONCLUSIONS: These data indicate that OX-A plays an inhibitory role in GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth, nutritional status and sleep regulation.

scholarly journals MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1291
Author(s):  
Jean A. Boutin ◽  
Magali Jullian ◽  
Lukasz Frankiewicz ◽  
Mathieu Galibert ◽  
Philippe Gloanec ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Parent Compound ◽  
Insulin Level ◽  
Antagonistic Effect ◽  
Melanin Concentrating Hormone ◽  
The Brain ◽  
Nanomolar Range ◽  
Obesity Syndrome ◽  
Final Work

Melanin-concentrating hormone (MCH) is a 19 amino acid long peptide found in the brain of animals, including fishes, batrachians, and mammals. MCH is implicated in appetite and/or energy homeostasis. Antagonists at its receptor (MCH-R1) could be major tools (or ultimately drugs) to understand the mechanism of MCH action and to fight the obesity syndrome that is a worldwide societal health problem. Ever since the deorphanisation of the MCH receptor, we cloned, expressed, and characterized the receptor MCH-R1 and started a vast medicinal chemistry program aiming at the discovery of such usable compounds. In the present final work, we describe GPS18169, a pseudopeptide antagonist at the MCH-R1 receptor with an affinity in the nanomolar range and a Ki for its antagonistic effect in the 20 picomolar range. Its metabolic stability is rather ameliorated compared to its initial parent compound, the antagonist S38151. We tested it in an in vivo experiment using high diet mice. GPS18169 was found to be active in limiting the accumulation of adipose tissues and, correlatively, we observed a normalization of the insulin level in the treated animals, while no change in food or water consumption was observed.

scholarly journals In vivo detection of optically-evoked opioid peptide release

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ream Al-Hasani ◽  
Jenny-Marie T Wong ◽  
Omar S Mabrouk ◽  
Jordan G McCall ◽  
Gavin P Schmitz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Opioid Peptide ◽  
Neuronal Circuitry ◽  
Endogenous Peptide ◽  
In Vivo Detection ◽  
Highly Sensitive ◽  
Peptide Release ◽  
Freely Moving ◽  
The Brain

Though the last decade has seen accelerated advances in techniques and technologies to perturb neuronal circuitry in the brain, we are still poorly equipped to adequately dissect endogenous peptide release in vivo. To this end we developed a system that combines in vivo optogenetics with microdialysis and a highly sensitive mass spectrometry-based assay to measure opioid peptide release in freely moving rodents.

scholarly journals Injectable Nanoelectrodes Enable Wireless Deep Brain Stimulation of Native Tissue in Freely Moving Mice

2020 ◽  
Author(s):  
Kristen L. Kozielski ◽  
Ali Jahanshahi ◽  
Hunter B. Gilbert ◽  
Yan Yu ◽  
Önder Erin ◽  
...  
Keyword(s):  
Behavioral Changes ◽  
Less Invasive ◽  
Magnetoelectric Materials ◽  
The Central Nervous System ◽  
Freely Moving ◽  
The Brain ◽  
Deep Brain ◽  
Stimulation Of

AbstractDevices that electrically modulate the central nervous system have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices typically have centimeter-scale dimensions, requiring surgical implantation and wired-in powering. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Herein, we present injectable magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of the brain, and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

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