UPLC-MS/MS method for determination of schisandrin in rat plasma and brain microdialysates: application to a comparative pharmacokinetic and brain distribution study in normal and Alzheimer’s disease rats

2017 ◽  
Vol 9 (32) ◽  
pp. 4740-4746 ◽  
Author(s):  
BinBin Wei ◽  
Mingyan Liu ◽  
Zaixing Chen ◽  
Minjie Wei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Plasma ◽  
Brain Distribution ◽  
Comparative Pharmacokinetic ◽  
Distribution Study

An efficient UPLC-MS/MS method for determining schisandrin in rat plasma and brain microdialysates has been developed and validated.

Neuropeptides in Alzheimer’s Disease: An Update

2019 ◽  
Vol 16 (6) ◽  
pp. 544-558 ◽  
Author(s):  
Carla Petrella ◽  
Maria Grazia Di Certo ◽  
Christian Barbato ◽  
Francesca Gabanella ◽  
Massimo Ralli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Potential Role ◽  
Brain Distribution ◽  
Brain Areas ◽  
Small Proteins ◽  
Current Review ◽  
The Central Nervous System ◽  
Available Information

Neuropeptides are small proteins broadly expressed throughout the central nervous system, which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated the involvement of many neuropeptides in both neurophysiological functions and neuropathological conditions, among which is Alzheimer’s disease (AD). The role exerted by neuropeptides in AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain areas responsible for learning and memory processes. Confirming this point, it has been demonstrated that numerous neuropeptide-containing neurons are pathologically altered in brain areas of both AD patients and AD animal models. Furthermore, the levels of various neuropeptides have been found altered in both Cerebrospinal Fluid (CSF) and blood of AD patients, getting insights into their potential role in the pathophysiology of AD and offering the possibility to identify novel additional biomarkers for this pathology. We summarized the available information about brain distribution, neuroprotective and cognitive functions of some neuropeptides involved in AD. The main focus of the current review was directed towards the description of clinical data reporting alterations in neuropeptides content in both AD patients and AD pre-clinical animal models. In particular, we explored the involvement in the AD of Thyrotropin-Releasing Hormone (TRH), Cocaine- and Amphetamine-Regulated Transcript (CART), Cholecystokinin (CCK), bradykinin and chromogranin/secretogranin family, discussing their potential role as a biomarker or therapeutic target, leaving the dissertation of other neuropeptides to previous reviews.

A ratiometric electrochemical strategy for sensitive determination of Furin activity based on dual signal amplification and antifouling nanosurfaces

The Analyst ◽  
2017 ◽  
Vol 142 (22) ◽  
pp. 4215-4220 ◽  
Author(s):  
Dazhi Yao ◽  
Wenqi Zhao ◽  
Limin Zhang ◽  
Yang Tian
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Signal Amplification ◽  
Accurate Method ◽  
Sensitive Determination ◽  
Dual Signal Amplification

Developing a sensitive and accurate method for Furin activity is still the bottleneck for understanding the role played by Furin in cell-surface systems and even in Alzheimer's disease.

Automatic determination of white matter hyperintensity properties in relation to the development of Alzheimer's disease

2016 ◽  
Author(s):  
Sandra van der Velden ◽  
Christoph Moenninghoff ◽  
Isabel Wanke ◽  
Martha Jokisch ◽  
Christian Weimar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
White Matter Hyperintensity ◽  
Automatic Determination

scholarly journals SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Tobias Gustavsson ◽  
Stina Syvänen ◽  
Paul O’Callaghan ◽  
Dag Sehlin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ex Vivo ◽  
Photon Emission ◽  
Amyloid Β ◽  
Emission Computed Tomography ◽  
Brain Uptake ◽  
Brain Distribution ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Abstract Background Alzheimer’s disease (AD) immunotherapy with antibodies targeting amyloid-β (Aβ) has been extensively explored in clinical trials. The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants – RmAb158, the recombinant murine version of BAN2401, which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients, and the bispecific RmAb158-scFv8D3, which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis. Methods A single intravenous injection of iodine-125 (125I)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice (tg-ArcSwe). In vivo single-photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks. Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβ and CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with Aβ. Results Despite faster blood clearance, [125I]RmAb158-scFv8D3 displayed higher brain exposure than [125I]RmAb158 throughout the study. The brain distribution of [125I]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology, while [125I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times. Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for [125I]RmAb158-scFv8D3, whereas [125I]RmAb158 displayed retention and Aβ interactions in lateral ventricles. Conclusions The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging. Moreover, it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy.

scholarly journals Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Bo Li ◽  
Min Lu ◽  
Lei Jin ◽  
Maoen Zheng ◽  
Peilu Sun ◽  
...  
Keyword(s):  
High Performance ◽  
Brain Homogenate ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Brain Distribution ◽  
Single Oral Administration ◽  
Mass Spectrometric Detector ◽  
Distribution Studies ◽  
Lower Limits

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.

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