An enzyme has been discovered and characterized from Silene cucubalus cell suspension cultures that catalyzes the transfer of the y-glutamylcysteine dipeptide moiety of glutathione to an acceptor glutathione molecule or a growing chain of [Glu(-Cys)],-Gly oligomers, thus synthesizing phytochelatins, the metal-binding peptides of higher plants and select fungi. The enzyme was named y-glutamylcysteine dipeptidyl transpeptidase and given the trivial name phytochelatin synthase. The primary reaction catalyzed is [Glu(-Cys)]-Gly + [Glu(-Cys)],,-Gly -* [Glu(-Cys)],k+-Gly + Gly. The enzyme is isoelectric near pH 4.8 and has temperature and pH optima at 35'C and 7.9, respectively. Phytochelatin synthase is constitutively present in cell cultures of various plant species and its formation is not noticeably induced by heavy metal ions in the growth medium. The enzyme (Mr 95,000) seems to be composed of four subunits, the dimer (Mr 50,000) being also catalytically active. Cd2+ is by far the best metal activator of the enzyme followed by Ag+, Bi3+, Pb2+, Zn2+, Cu2+, Hg2+, and Au+. The Km for glutathione is 6.7 mM. The enzyme activity seems to be self-regulated in that the product of the reaction (the phytochelatins) chelates the enzyme-activating metal, thus terminating the enzyme reaction. The molar ratio of the y-glutamylcysteine dipeptide in phytochelatin to Cd2+ in the newly formed complex was 2:1.

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A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e., replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat's brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS) cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes.

Membrane transporters have long been utilized to improve the oral, hepatic, and renal (re)absorption. In the brain, however, the transporter-mediated drug delivery has not yet been fully achieved due to the complexity of the blood−brain barrier (BBB). Because L-type amino acid transporter 1 (LAT1) is a good candidate to improve the brain delivery, we developed here four novel LAT1-utilizing prodrugs of four nonsteroidal anti-inflammatory drugs. As a result, all the prodrugs were able to cross the BBB and localize into the brain cells. The brain uptake of salicylic acid (SA) was improved five times, not only across the mouse BBB but also into the cultured mouse and human brain cells. The naproxen prodrug was also transported efficiently into the mouse brain achieving less peripheral exposure, but the brain release of naproxen from the prodrug was not improved. Contrarily, the high plasma protein binding of the flurbiprofen prodrug and the premature bioconversion of the ibuprofen prodrug in the mouse blood hindered the efficient brain delivery. Thus, the structure of the parent drug affects the successful brain delivery of the LAT1-utilizing prodrugs, and the small-sized LAT1-utilizing prodrug of SA constituted a successful model to specifically deliver its parent drug across the mouse BBB and into the cultured mouse and human brain cells.

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Abstract:Organic bioelectronics forms the basis of conductive polymer tools with great potential for application in biomedical science and medicine. It is a rapidly growing field of both academic and industrial interest since conductive polymers bridge the gap between electronics and biology by being electronically and ionically conductive. This feature can be employed in numerous ways by choosing the right polyelectrolyte system and tuning its properties towards the intended application. This review highlights how active organic bioelectronic surfaces can be used to control cell attachment and release as well as to trigger cell signaling by means of electrical, chemical or mechanical actuation. Furthermore, we report on the unique properties of conductive polymers that make them outstanding materials for labeled or label-free biosensors. Techniques for electronically controlled ion transport in organic bioelectronic devices are introduced, and examples are provided to illustrate their use in self-regulated medical devices. Organic bioelectronics have great potential to become a primary platform in future bioelectronics. We therefore introduce current applications that will aid in the development of advanced in vitro systems for biomedical science and of automated systems for applications in neuroscience, cell biology and infection biology. Considering this broad spectrum of applications, organic bioelectronics could lead to timely detection of disease, and facilitate the use of remote and personalized medicine. As such, organic bioelectronics might contribute to efficient healthcare and reduced hospitalization times for patients. OPEN ACCESSElectronics 2015, 4 880

Content List -Read more articles from the symposium: 13th Key Symposium -Bioelectronic Medicine: Technology Targeting Molecular Mechanisms.Abstract. L€ offler S, Melican K, Richter-Dahlfors A.

A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 μm axial resolution was used. A composite 125 μm diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 μm) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.