ChemInform Abstract: Photocontrol of Neural Activity: Biophysical Mechanisms and Performance in vivo

ChemInform ◽  
2008 ◽  
Vol 39 (33) ◽  
Author(s):  
Lucas Sjulson ◽  
Gero Miesenboeck
Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 710
Author(s):  
Tanja Ilić ◽  
Ivana Pantelić ◽  
Snežana Savić

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Maria Natalia Calienni ◽  
Daniela Maza Vega ◽  
C. Facundo Temprana ◽  
María Cecilia Izquierdo ◽  
David E. Ybarra ◽  
...  

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.


2020 ◽  
Vol 39 (1) ◽  
pp. 209-221
Author(s):  
Jiafeng Wan ◽  
Xiaoyuan Zhang ◽  
Kai Zhang ◽  
Zhiqiang Su

Abstract In recent years, nanomaterials have attracted lots of attention from researchers due to their unique properties. Nanometer fluorescent materials, such as organic dyes, semiconductor quantum dots (QDs), metal nano-clusters (MNCs), carbon dots (CDs), etc., are widely used in biological imaging due to their high sensitivity, short response time, and excellent accuracy. Nanometer fluorescent probes can not only perform in vitro imaging of organisms but also achieve in vivo imaging. This provides medical staff with great convenience in cancer treatment. Combined with contemporary medical methods, faster and more effective treatment of cancer is achievable. This article explains the response mechanism of three-nanometer fluorescent probes: the principle of induced electron transfer (PET), the principle of fluorescence resonance energy transfer (FRET), and the principle of intramolecular charge transfer (ICT), showing the semiconductor QDs, precious MNCs, and CDs. The excellent performance of the three kinds of nano fluorescent materials in biological imaging is highlighted, and the application of these three kinds of nano fluorescent probes in targeted biological imaging is also introduced. Nanometer fluorescent materials will show their significance in the field of biomedicine.


2009 ◽  
Vol 12 (01) ◽  
pp. 21-43 ◽  
Author(s):  
BINHUA TANG ◽  
LI HE ◽  
QING JING ◽  
BAIRONG SHEN

The loss of cell cycle control is often associated with cancers and other different diseases. With the accumulation of omics data, the network for molecule interactions in the cell cycle process will become much clearer. The identification of the crucial modules in a giant network and investigation of inherent control relations are very important to the understanding of the molecular mechanisms of diseases for new drug design. The paper proposes novel techniques in analyzing such core regulatory modules based on network and system control theories. We initially define the degree of participation (DOP) and the rate of activity (ROA) for indentifying core module components, and then the diverse contribution elasticity functions for quantifying pairwise regulatory or control activities between those components, thus facilitating the decomposition of expanded core modules and the formation of feedback loops within the control schema. Motivated by the inherent regulatory mechanisms, we expound a kind of multiphase nonlinear adaptive control algorithm in repelling abnormal genetic mutations, which directly and indirectly impact cancer development in biological cells and organs. Experimental predictions are also elucidated within the work, helping those in vivo design, verification and performance evaluation.


1990 ◽  
Vol 12 (2) ◽  
pp. 132-143 ◽  
Author(s):  
Deborah L. Feltz ◽  
Camala A. Riessinger

An experiment was conducted to investigate the relative merits of in vivo emotive imagery and performance feedback in enhancing self-efficacy beliefs and performance on a competitive muscular endurance task. College males (n=60) and females (n=60) were randomly assigned to one of three conditions: mastery imagery plus feedback, feedback alone, or control condition. Subjects in the imagery-plus-feedback condition were told that one of the pair (always the subject) would receive imagery exposure while the other (always the confederate) would wait outside. Subjects performed two trials against the confederate, who always won by 10 seconds. A Group x Trials interaction for self-efficacy revealed a significant increase for the imagery group after brief exposure. Also, imagery subjects had significantly higher efficacy scores than feedback alone or control subjects after each performance trial. A Group x Trials interaction for performance indicated that imagery subjects initially had significantly longer performance times than did feedback alone or control subjects. Performance feedback alone did not influence efficacy beliefs or performance.


2008 ◽  
Vol 15 (4) ◽  
pp. 468-484 ◽  
Author(s):  
Timothy J. Corbett ◽  
Anthony Callanan ◽  
Liam G. Morris ◽  
Barry J. Doyle ◽  
Pierce A. Grace ◽  
...  

2021 ◽  
Vol 2021 (9) ◽  
pp. pdb.prot106872
Author(s):  
Ayako Yamaguchi

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.


2020 ◽  
Vol 30 (34) ◽  
pp. 2000896
Author(s):  
Ji‐Won Seo ◽  
Kiup Kim ◽  
Ki‐Won Seo ◽  
Mi Kyung Kim ◽  
Sohyeon Jeong ◽  
...  
Keyword(s):  

2020 ◽  
Vol 12 ◽  
Author(s):  
Emma Arvidsson ◽  
Sarolta Gabulya ◽  
Alvin Tore Brodin ◽  
Tobias Erik Karlsson ◽  
Lars Olson

Structural synaptic reorganizations needed to permanently embed novel memories in the brain involve complex plasticity-enhancing and plasticity-inhibiting systems. Increased neural activity is linked to rapid downregulation of Nogo receptor 1 (NgR1), needed to allow local structural synaptic plasticity. This local regulation of plasticity is thought to be moderated by global systems, such as the ascending cholinergic and monoaminergic systems, adding significance to locally increased neural activity. Here we address the reverse possibility that the global systems may also be influenced by the status of local plasticity. Using NgR1-overexpressing mice, with impaired plasticity and long-term memory, we measured the ability to release dopamine (DA), implicated in regulating plasticity and memory. In vivo chronoamperometric recording with high temporal and spatial resolution revealed severe impairment of potassium chloride (KCl)-induced increase of extracellular DA in the dorsal striatum of mice overexpressing NgR1 in forebrain neurons. A similar, but lesser, impairment of DA release was seen following amphetamine delivery. In contrast, potassium chloride-evoked DA release in NgR1 knockout (KO) mice led to increased levels of extracellular DA. That NgR1 can impair DA signaling, thereby further dampening synaptic plasticity, suggests a new role for NgR1 signaling, acting in synergy with DA signaling to control synaptic plasticity.Significance Statement:The inverse correlation between local NgR1 levels and magnitude of KCl-inducible amounts of DA release in the striatum reinforces the rule of NgR1 as a regulator of structural synaptic plasticity and suggests synergy between local and global plasticity regulating systems.


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