Enhancement of availability of cloricromene at brain level by a lipophilic prodrug

Transcranial alternating current stimulation (tACS) has emerged as a promising technique to non-invasively modulate the endogenous oscillations in the human brain. Despite its clinical potential to be applied in routine rehabilitation therapies, the underlying modulation mechanism has not been thoroughly understood, especially for patients with neurological disorders, including stroke. In this study, we aimed to investigate the frequency-specific stimulation effect of tACS in chronic stroke. Thirteen chronic stroke patients underwent tACS intervention, while resting-state functional magnetic resonance imaging (fMRI) data were collected under various frequencies (sham, 10 Hz and 20 Hz). The graph theoretical analysis indicated that 20 Hz tACS might facilitate local segregation in motor-related regions and global integration at the whole-brain level. However, 10 Hz was only observed to increase the segregation from whole-brain level. Additionally, it is also observed that, for the network in motor-related regions, the nodal clustering characteristic was decreased after 10 Hz tACS, but increased after 20 Hz tACS. Taken together, our results suggested that tACS in various frequencies might induce heterogeneous modulation effects in lesioned brains. Specifically, 20 Hz tACS might induce more modulation effects, especially in motor-related regions, and they have the potential to be applied in rehabilitation therapies to facilitate neuromodulation. Our findings might shed light on the mechanism of neural responses to tACS and facilitate effectively designing stimulation protocols with tACS in stroke in the future.

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Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma [Corrigendum]

International Journal of Nanomedicine ◽

10.2147/ijn.s145516 ◽

2017 ◽

Vol Volume 12 ◽

pp. 5119-5120

Author(s):

Anna Alekseeva ◽

Ekaterina Moiseeva ◽

Natalia Onishchenko ◽

Ivan Boldyrev ◽

Alexander Singin ◽

...

Keyword(s):

T Cell ◽

Tumor Cells ◽

Liposomal Formulation ◽

Lipophilic Prodrug

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[18F]FBAU 3′,5′-dibenzoate, a lipophilic prodrug, enhances brain uptake of the cell proliferation tracer [18F]FBAU

Nuclear Medicine and Biology ◽

10.1016/j.nucmedbio.2008.04.004 ◽

2008 ◽

Vol 35 (5) ◽

pp. 635-643 ◽

Cited By ~ 2

Author(s):

Chih-Hao K. Kao ◽

Heng-Li Xie ◽

Chia-Hsin Liao ◽

Wen-Min Chen ◽

Pan-Fu Kao

Keyword(s):

Cell Proliferation ◽

Brain Uptake ◽

Lipophilic Prodrug

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Demonstrating brain-level interactions between working memory load and frustration while driving using functional near-infrared spectroscopy

Frontiers in Human Neuroscience ◽

10.3389/conf.fnhum.2018.227.00091 ◽

2018 ◽

Vol 12 ◽

Author(s):

Anirudh Unni ◽

Benedikt Kretzmeyer ◽

Klas Ihme ◽

Frank Koester ◽

Meike Jipp ◽

...

Keyword(s):

Working Memory ◽

Infrared Spectroscopy ◽

Near Infrared Spectroscopy ◽

Near Infrared ◽

Memory Load ◽

Working Memory Load ◽

Functional Near Infrared Spectroscopy ◽

Brain Level

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Demonstrating brain-level interactions between working memory load and driving demand level using fNIRS

Frontiers in Human Neuroscience ◽

10.3389/conf.fnhum.2018.227.00141 ◽

2018 ◽

Vol 12 ◽

Author(s):

Jochem Rieger ◽

Jakob Scheunemann ◽

Klas Ihme ◽

Frank Köster ◽

Meike Jipp ◽

...

Keyword(s):

Working Memory ◽

Memory Load ◽

Working Memory Load ◽

Brain Level

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Exploring the dynamic mechanisms of steady-state visual evoked potentials at the whole-brain level: evidence from a computational study

10.1101/2021.02.05.429877 ◽

2021 ◽

Author(s):

Ge Zhang ◽

Yan Cui ◽

Yangsong Zhang ◽

Hefei Cao ◽

Guanyu Zhou ◽

...

Keyword(s):

Steady State ◽

Evoked Potentials ◽

Visual Evoked Potentials ◽

Large Scale ◽

Whole Brain ◽

Frequency Sensitivity ◽

Dynamic Mechanisms ◽

Brain Level ◽

The Brain ◽

Visual Evoked

AbstractPeriodic visual stimulation can induce stable steady-state visual evoked potentials (SSVEPs) distributed in multiple brain regions and has potential applications in both neural engineering and cognitive neuroscience. However, the underlying dynamic mechanisms of SSVEPs at the whole-brain level are still not completely understood. Here, we addressed this issue by simulating the rich dynamics of SSVEPs with a large-scale brain model designed with constraints of neuroimaging data acquired from the human brain. By eliciting activity of the occipital areas using an external periodic stimulus, our model was capable of replicating both the spatial distributions and response features of SSVEPs that were observed in experiments. In particular, we confirmed that alpha-band (8-12 Hz) stimulation could evoke stronger SSVEP responses; this frequency sensitivity was due to nonlinear resonance and could be modulated by endogenous factors in the brain. Interestingly, the stimulus-evoked brain networks also exhibited significant superiority in topological properties near this frequency-sensitivity range, and stronger SSVEP responses were demonstrated to be supported by more efficient functional connectivity at the neural activity level. These findings not only provide insights into the mechanistic understanding of SSVEPs at the whole-brain level but also indicate a bright future for large-scale brain modeling in characterizing the complicated dynamics and functions of the brain.

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Lymphatic Targeting of Anti-Human Immunodeficiency Virus Nucleosides: Pharmacokinetics of G′-Deoxy-2′,3′-Didehydrothymidine after Intravenous and Oral Administration of Dipalmitoylphosphatidyl Prodrug to Mice

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029700800503 ◽

1997 ◽

Vol 8 (5) ◽

pp. 409-415 ◽

Cited By ~ 2

Author(s):

KK Manouilov ◽

Z-S Xu ◽

LS Manouilova ◽

FD Boudinot ◽

RF Schinazi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Lymph Nodes ◽

Extended Release ◽

Lymphatic System ◽

Parent Compound ◽

Equimolar Dose ◽

Lipophilic Prodrug ◽

Immunodeficiency Virus ◽

Intravenous And Oral Administration ◽

Therapy Strategies

The lymphatic system is a primary target for early anti-human immunodeficiency virus drug therapy. Strategies are currently being sought to enhance the delivery of nucleoside analogues such as 3′-deoxy-2′,3′-didehydrothymidine (stavudine; d4T) toward the lymph and lymph nodes. The purpose of this study was to synthesize dipalmitoylphosphatidyl-d4T (DPP-d4T) as a lipophilic prodrug of d4T and to evaluate the lymphatic distribution of d4T following administration of d4T and DPP-d4T to mice. The pharmacokinetics of d4T were characterized following administration of a single intravenous or oral dose of 50 mg kg−1 d4T and an equimolar dose (214 mg kg−1) of DPP-d4T. Concentrations of d4T in serum and lymph nodes were determined by HPLC. Following administration of d4T, the distribution of d4T into lymph nodes was rapid with maximum concentrations observed within 5 min after dosing. The AUC and half-life values of d4T in three groups of lymph nodes were similar to those in serum. Administration of DPP-d4T resulted in significantly lower concentrations of d4T in serum and lymph nodes. Approximately 67% of the intravenously administered DPP-d4T was biotransformed to parent compound. The apparent oral bioavailability of DPP-d4T was low. While the phospholipid prodrug did not increase d4T concentrations in the lymph nodes, it did provide an extended release of the parent nucleoside, resulting in sustained concentrations of d4T.

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Modeling Self-Efficacy as a Dynamic Cognitive Process with the Computational-Unified Learning Model (C-ULM)

International Journal of Cognitive Informatics and Natural Intelligence ◽

10.4018/ijcini.2015070101 ◽

2015 ◽

Vol 9 (3) ◽

pp. 1-24 ◽

Cited By ~ 4

Author(s):

Duane F. Shell ◽

Leen-Kiat Soh ◽

Vlad Chiriacescu

Keyword(s):

Neural Plasticity ◽

Self Efficacy ◽

Teaching And Learning ◽

Learning Task ◽

Human Action ◽

Learning Model ◽

Cognitive Computing ◽

Brain Level ◽

Subjective Confidence ◽

Model C

Self-efficacy is a person's subjective confidence in their capability of effectively executing behaviors and actions including problem solving. Research has shown it to be one of the most powerful motivators of human action and strongest predictors of performance across a variety of domains. This paper reports on the computational modeling of self-efficacy based on principles derived from the Unified Learning Model (ULM) as instantiated in the multi-agent Computational ULM (C-ULM). The C-ULM simulation is unique in tying self-efficacy directly to the evolution of knowledge itself and in dynamically updating self-efficacy at each step during learning and task attempts. Self-efficacy beliefs have been associated with neural and brain level cognitive processes. Because C-ULM models statistical learning consistent with neural plasticity, the C-ULM simulation provides a model of self-efficacy that is more compatible with neural and brain level instantiation. Results from simulations of self-efficacy evolution due to teaching and learning, task feedback, and knowledge decay are presented. Implications for research into human motivation and learning, cognitive informatics, and cognitive computing are discussed.

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