Fwu-Shan Sheu

Pt–Pb alloy nanoparticle/carbon nanotube nanocomposite: a strong electrocatalyst for glucose oxidation

A Pt–Pb alloy nanoparticle/multi-walled carbon nanotube (Pt–Pb/MWCNT) nanocomposite was prepared by electrodepositing Pt–Pb alloy onto MWCNTs that were vertically aligned on Ta plates. The 10–40 nm diameter Pt–Pb alloy nanoparticles were mainly deposited at the tips, and sparsely dispersed on the sidewalls of the bamboo-like MWCNTs, as demonstrated by scanning electron microscopy, transmission electron microscopy (TEM), and x-ray diffraction. The high resolution TEM (HRTEM) image showed a snowflake-like morphology for the Pt–Pb nanoparticles. This Pt–Pb/MWCNT nanocomposite exhibited much stronger electrocatalytic activity toward glucose oxidation than pristine MWCNTs, Pt–Pb on glassy carbon, and Pt/MWCNT and Au/MWCNT nanocomposites, in both neutral and alkaline solutions. This Pt–Pb/MWCNT nanocomposite electrode is hence promising for development as a nonenzymatic glucose sensor.

Dissociation of Cortical Regions Modulated by Both Working Memory Load and Sleep Deprivation and by Sleep Deprivation Alone

Working memory is an important mental capacity that is compromised following sleep deprivation (SD). To understand how working memory load interacts with state to influence brain activation in load-sensitive regions, and the extent to which SD-related changes are common across different loads, we used fMRI to study twelve healthy subjects following 24 h of SD using a verbal n-back task with three load levels. Performance decline was observed by way of reduced accuracy and slower response times following SD. The left prefrontal region and thalamus showed load dependent activity modulation that interacted with state. The right parietal and anterior medial frontal regions showed load dependent changes in activity as well as an effect of state. The anterior cingulate and occipital regions showed activation that displayed state effects that were independent of working memory load. These findings represent a step toward identifying how different brain regions exhibit varying vulnerability to the deleterious effects of SD on working memory.

Technology behind commercial devices for blood glucose monitoring in diabetes management: A review

The blood glucose monitoring devices (BGMDs) are an integral part of diabetes management now-a-days. They have evolved tremendously within the last four decades in terms of miniaturization, rapid response, greater specificity, simplicity, minute sample requirement, painless sample uptake, sophisticated software and data management. This article aims to review the developments in the technologies behind commercial BGMD, especially those in the areas of chemistries, mediators and other components. The technology concerns, on-going developments and future trends in blood glucose monitoring (BGM) are also discussed.

Interfacing Carbon Nanotubes with Living Mammalian Cells and Cytotoxicity Issues

The unique structures and properties of carbon nanotubes (CNTs) have attracted extensive investigations for many applications, such as those in the field of biomedical materials and devices, biosensors, drug delivery, and tissue engineering. Anticipated large-scale productions for numerous diversified applications of CNTs might adversely affect the environment and human health. For successful applications in the biomedical field, the issue of interfacing between CNTs and mammalian cells in vitro needs to be addressed before in vivo studies can be carried out systematically. We review the important studies pertaining to the internalization of CNTs into the cells and the culturing of cells on the CNT-based scaffold or support materials. The review will focus on the description of a variety of factors affecting CNT cytotoxicity: type of CNTs, impurities, lengths of CNTs, aspect ratios, dispersion, chemical modification, and assaying methods of cytotoxicity.

Frontal cortical α7 and α4β2 nicotinic acetylcholine receptors in working and reference memory

The alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimers disease, but the subtype-specific role of frontal cortical nAchRs in memory has not been well characterized. Hence, we sought to understand the role of frontal cortical alpha7 and alpha4beta2 nAchR subtypes in both working and reference memory by observing the effects of subtype specific agonists and antagonists on radial arm maze performance. It was found that alpha7 nAchRs in the frontal cortex are involved in working and reference memory, while alpha4beta2 nAchRs are only involved in working memory. Throughout the study, drug treatments did not affect motor functionality in the animals. Our data thus sheds further light on the frontal cortex as an important anatomical locus for nAchR-mediated memory function in the brain, and highlights the differing role of alpha7 and alpha4beta2 nAchRs in long and short term memory.

Hypochlorous acid induces apoptosis of cultured cortical neurons through activation of calpains and rupture of lysosomes

3‐Chlorotyrosine, a bio‐marker of hypochlorous acid (HOCl) in vivo, was reported to be substantially elevated in the Alzheimers disease (AD) brains. Thus, HOCl might be implicated in the development of AD. However, its effect and mechanism on neuronal cell death have not been investigated. Here, we report for the first time that HOCl treatment induces an apoptotic‐necrotic continuum of concentration‐dependent cell death in cultured cortical neurons. Neurotoxicity caused by an intermediate concentration of HOCl (250 µm) exhibited several biochemical markers of apoptosis in the absence of caspase activation. However, the involvement of calpains was demonstrated by data showing that calpain inhibitors protect cortical neurons from apoptosis and the formation of 145/150 kDa α‐fodrin fragments. Moreover, an increase in cytosolic Ca2+ concentration was associated with HOCl neurotoxicity and Ca2+ channel antagonists, and Ca2+ chelators prevented cleavage of α‐fodrin and the induction of apoptosis. Finally, we found that calpain activation ruptured lysosomes. Stabilization of lysosomes by calpain inhibitors or imidazoline drugs, as well as inhibition of cathepsin protease activities, rescued cells from HOCl‐induced neurotoxicity. Our results showed for the first time that HOCl induces apoptosis in cortical neurons, and that the cell death process involves calpain activation and rupture of lysosomes.

Nanostructured platinum-lipid bilayer composite as biosensor.

The present work describes the preparation of supported bilayer lipid membrane (s-BLM) doped with metal nanoparticles for the design of biosensors. Platinum (Pt) nanoparticles were deposited through s-BLM to build a hybrid device of nanoscale electrode array by potential cycling in 1 mM K(2)PtCl(6) solution containing 0.1 M KCl. The properties of Pt nanoparticle-doped s-BLM composite were then characterized by cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM). Our results showed that Pt nanoparticles grew in voids of the s-BLMs, through which the underlying glassy carbon (GC) electrode was connected, with maximum length extended out of the lipid membrane around 40 nm. Doping of Pt nanoparticles through s-BLM increased the membrane capacitance and decreased the membrane resistance of s-BLM. Pt nanoparticles array in s-BLM electrocatalyzed the reduction of oxygen (O(2)) in phosphate buffer solution (PBS). Practical application of Pt nanoparticle-doped s-BLM for the construction of glucose biosensor was also demonstrated in terms of its dose-response curve, stability and reproducibility. Thus, lipid membrane doped with Pt nanoparticles is a novel electrode system at nanoscale that can penetrate through the insulating membrane to probe molecular recognition and catalytic events at the lipid membrane-solution interface.

Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra.

Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (Plumen) was approximately 7-fold higher than that based on drug appearance in the blood (Pblood). Glabridin was mainly metabolized by glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides abolished the polarized transport of glabridin across Caco-2 cells. Incubation of verapamil significantly altered the intracellular accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was significantly higher in MDCKII cells overexpressing PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of digoxin with an IC50 value of 2.56 μM, but stimulated PgP/MDR1 ATPase activity with a Km of 25.1 μM. The plasma AUC0–24h of glabridin in mdr1a(–/–) mice was 3.8-fold higher than that in wild-type mice. These findings indicate that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and first-pass metabolism contribute to the low oral bioavailability of glabridin.

Graphene versus Multi-Walled Carbon Nanotubes for Electrochemical Glucose Biosensing

A simple procedure was developed for the fabrication of electrochemical glucose biosensors using glucose oxidase (GOx), with graphene or multi-walled carbon nanotubes (MWCNTs). Graphene and MWCNTs were dispersed in 0.25% 3-aminopropyltriethoxysilane (APTES) and drop cast on 1% KOH-pre-treated glassy carbon electrodes (GCEs). The EDC (1-ethyl-(3-dimethylaminopropyl) carbodiimide)-activated GOx was then bound covalently on the graphene- or MWCNT-modified GCE. Both the graphene- and MWCNT-based biosensors detected the entire pathophysiological range of blood glucose in humans, 1.4–27.9 mM. However, the direct electron transfer (DET) between GOx and the modified GCE’s surface was only observed for the MWCNT-based biosensor. The MWCNT-based glucose biosensor also provided over a four-fold higher current signal than its graphene counterpart. Several interfering substances, including drug metabolites, provoked negligible interference at pathological levels for both the MWCNT- and graphene-based biosensors. However, the former was more prone to interfering substances and drug metabolites at extremely pathological concentrations than its graphene counterpart.

Do Mitochondria make Nitric Oxide? No?

Several papers have claimed that mitochondria contain nitric oxide synthase (NOS) and make nitric oxide (NO•) in amounts sufficient to affect mitochondrial respiration. However, we found that the addition of l-arginine or the NOS inhibitor l-NMMA to intact rat liver mitochondria did not have any effect on the respiratory rate in both State 3 and State 4. We did not detect mitochondrial NO• production by the oxymyoglobin oxidation assay, or electrochemically using an NO• electrode. An apparent NO• production detected by the Griess assay was identified as an artifact. NO• generated by eNOS added to the mitochondria could easily be detected, although succinate-supplemented mitochondria appeared to consume NO•. Our data show that NO• production by normal rat liver mitochondria cannot be detected in our laboratory, even though the levels of production claimed in the literature should easily have been measured by the techniques used. The implications for the putative mitochondrial NOS are discussed.