Inhibition of the unique repolarisation K+ channel current IKur by verapamil in human atrial myocytes

Abstract no. CVS-03published_or_final_versio

A Thermal Management System to Reuse Thermal Waste Released by High-Power Light-Emitting Diodes

© 1963-2012 IEEE. In this article, a comprehensive and efficient thermal management system is proposed to harvest and reuse the thermal waste of high-power light-emitting diodes (HP-LEDs) for the first time. Besides a conventional cooling system, including a thermoelectric (TE) cooler (TEC), a heatsink, and a fan, the proposed thermal management system also employs a TE generator (TEG), a temperature sensor, a voltage boost converter, and a microcontroller for thermal waste recycling. In this system, some of the thermal waste released by the HP-LED is harvested by the TEG and converted into electrical energy. With the help of a voltage boost converter, the harvested electrical power is used to power a temperature sensor for monitoring the surface temperature of the HP-LED. The entire system is regulated by the microcontroller. The system is elaborately established, tested, and the results are discussed. The experimental results show that the proposed system has an output electrical power of approximately 696.5μW , which is used to power a temperature sensor as a demonstration. The sensor works well, and the discrepancy of the surface temperature of the HP-LED measured by the sensor and by a thermometer is less than 5.38%, which validates the proposed thermal management system

Investigating the effects of particle shape on normal compression and overconsolidation using DEM

Discrete element modelling of normal compression has been simulated on a sample of breakable two-ball clumps and compared to that of spheres. In both cases the size effect on strength is assumed to be that of real silica sand. The slopes of the normal compression lines are compared and found to be consistent with the proposed equation of the normal compression line. The values of the coefficient of earth pressure at rest K0,nc are also compared and related to the critical state fiction angles for the two materials. The breakable samples have then been unloaded to establish the stress ratios on unloading. At low overconsolidation ratios the values of K0 follow a well-established empirical relationship and realistic Poisson ratios are observed. On progressive unloading both samples head towards passive failure, and the values of the critical state lines in extension in q–p' space are found to be consistent with the critical state angles deduced from the values of K0 during normal compression. The paper highlights the important role of particle shape in governing the stress ratio during both normal compression and subsequent overconsolidation

Differential Effects of Tyrosine Kinase Inhibitors on Volume-sensitive Chloride Current in Human Atrial Myocytes: Evidence for Dual Regulation by Src and EGFR Kinases

To determine whether protein tyrosine kinase (PTK) modulates volume-sensitive chloride current (I Cl.vol) in human atrial myocytes and to identify the PTKs involved, we studied the effects of broad-spectrum and selective PTK inhibitors and the protein tyrosine phosphatase (PTP) inhibitor orthovanadate (VO 4 -3). I Cl.vol evoked by hyposmotic bath solution (0.6-times isosmotic, 0.6T) was enhanced by genistein, a broad-spectrum PTK inhibitor, in a concentration-dependent manner (EC 50 = 22.4 μM); 100 μM genistein stimulated I Cl.vol by 122.4 ± 10.6%. The genistein-stimulated current was inhibited by DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, 150 μM) and tamoxifen (20 μM), blockers of I Cl.vol. Moreover, the current augmented by genistein was volume dependent; it was abolished by hyperosmotic shrinkage in 1.4T, and genistein did not activate Cl - current in 1T. In contrast to the stimulatory effects of genistein, 100 μM tyrphostin A23 (AG 18) and A25 (AG 82) inhibited I Cl.vol by 38.2 ± 4.9% and 40.9 ± 3.4%, respectively. The inactive analogs, daidzein and tyrphostin A63 (AG 43), did not alter I Cl.vol. In addition, the PTP inhibitor VO 4 -3 (1 mM) reduced I Cl.vol by 53.5 ± 4.5% (IC 50 = 249.6 μM). Pretreatment with VO 4 -3 antagonized genistein-induced augmentation and A23- or A25-induced suppression of I Cl.vol. Furthermore, the selective Src-family PTK inhibitor PP2 (5 μM) stimulated I Cl.vol, mimicking genistein, whereas the selective EGFR (ErbB-1) kinase inhibitor tyrphostin B56 (AG 556, 25 μM) reduced I Cl.vol, mimicking A23 and A25. The effects of both PP2 and B56 also were substantially antagonized by pretreatment with VO 4 -3. The results suggest that I Cl.vol is regulated in part by the balance between PTK and PTP activity. Regulation is complex, however. Src and EGFR kinases, distinct soluble and receptor-mediated PTK families, have opposing effects on I Cl.vol, and multiple target proteins are likely to be involved.published_or_final_versio

Core/shell Eudragit/poly(ethylene oxide) fibers for site-specific release

Electrospinning was used to prepare core/shell fibers containing the active pharmaceutical ingredients indomethacin (IMC) or mebeverine hydrochloride (MB-HCl). The shell of the fibers was fabricated from the pH sensitive Eudragit S100 polymer, while the drug-loaded core was based on the mucoadhesive polyethylene oxide (PEO). Three different drug loadings (from 9–23% w/w of the core mass) were prepared, and for MB-HCl two different molecular weights of PEO were explored. The resultant fibers generally comprise smooth cylinders, although in some cases defects such as surface particles or flattened or merged fibers were visible. Transmission electron microscopy showed all the systems to have clear core and shell compartments. The drugs are present in the amorphous physical form in the fibers. Dissolution tests found that the fibers can effectively prevent release in acidic conditions representative of the stomach, particularly for the acidic indomethacin. After transfer to a pH 7.4 medium, sustained release over between 6 and 22 h is observed. Given the mucoadhesive nature of the PEO core, after dissolution of the shell the fibers will be able to adhere to the walls of the intestinal tract and give sustained local drug release. This renders them promising for the treatment of conditions such as irritable bowel disease and colon cancer

Direct jet coaxial electrospinning of axon-mimicking fibers for diffusion tensor imaging

Hollow polymer microfibers with variable microstructural and hydrophilic properties were proposed as building elements to create axon-mimicking phantoms for validation of diffusion tensor imaging (DTI). The axon-mimicking microfibers were fabricated in a mm-thick 3D anisotropic fiber strip, by direct jet coaxial electrospinning of PCL/polysiloxane-based surfactant (PSi) mixture as shell and polyethylene oxide (PEO) as core. Hydrophilic PCL-PSi fiber strips were first obtained by carefully selecting appropriate solvents for the core and appropriate fiber collector rotating and transverse speeds. The porous cross-section and anisotropic orientation of axon-mimicking fibers were then quantitatively evaluated using two ImageJ plugins—nearest distance (ND) and directionality based on their scanning electron microscopy (SEM) images. Third, axon-mimicking phantom was constructed from PCL-PSi fiber strips with variable porous-section and fiber orientation and tested on a 3T clinical MR scanner. The relationship between DTI measurements (mean diffusivity [MD] and fractional anisotropy [FA]) of phantom samples and their pore size and fiber orientation was investigated. Two key microstructural parameters of axon-mimicking phantoms including normalized pore distance and dispersion of fiber orientation could well interpret the variations in DTI measurements. Two PCL-PSi phantom samples made from different regions of the same fiber strips were found to have similar MD and FA values, indicating that the direct jet coaxial electrospun fiber strips had consistent microstructure. More importantly, the MD and FA values of the developed axon-mimicking phantoms were mostly in the biologically relevant range

Electrospun organic–inorganic nanohybrids as sustained release drug delivery systems

In this work, the non-steroidal anti-inflammatory drugs ibuprofen (ibu) and ketoprofen (ket), both poorly soluble in water, were first intercalated into layered double hydroxide (LDH) nanoparticles. The drug–LDH composites were then mixed with poly(ε-caprolactone) (PCL) at 5% and 10% w/w ratios and processed into fibers via electrospinning, yielding organic–inorganic nanohybrids. PCL/drug fibers were additionally prepared as controls. The average diameter of the fibers ranged from 400 to 1000 nm. The fibers are found to be smooth and cylindrical, with the LDH-containing systems having more homogenous fibers than those without the inorganic filler. From in vitro drug release tests, it was determined that more than 90% of the intercalated ibu and ket were released from the drug–LDH nanohybrids within the first 4 hours. Similarly, more than 60% of the incorporated drug was freed from the PCL/drug fibers in this time period. However, the release rates of both ibu and ket from the drug–LDH loaded PCL fibers were significantly slower. Only 44–48% of ibu was released from the PCL/ibu–LDH system after 5 days, while the amount released in the case of ket was 20–25%. In addition, drug release was still ongoing after 5 days for all the PCL/drug–LDH samples. These systems are thus proposed to have potential as implantable drug delivery systems

Functionalized boron nanosheets as an intelligent nanoplatform for synergistic low-temperature photothermal therapy and chemotherapy

In this work, an innovative boron-based multifunctional nanoplatform was developed for synergistic chemotherapy/low temperature photothermal therapy (PTT). This platform is functionalized with a cRGD peptide to allow the targeting of αvβ3 integrin, which is over-expressed in the cells of tumors. The nanoparticles were further loaded with the chemotherapeutic drug doxorubicin (DOX) and a heat shock protein inhibitor (17AAG), and high loading capacities for both DOX (603 mg g−1 B-PEG-cRGD) and 17AAG (417 mg g−1) were obtained. The resultant DOX-17AAG@B-PEG-cRGD system shows both pH-controlled and near-infrared (NIR)-induced DOX and 17AAG release. It also provides significantly enhanced cellular uptake in cancerous cells over healthy cells. The presence of 17AAG allows low-temperature PTT to be combined with chemotherapy with DOX, resulting in highly effective anti-cancer activity. This has been confirmed by both in vitro assays and using an in vivo murine cancer model. It is expected that such a multifunctional nanoplatform can serve as a promising candidate for cancer therapy

Synthesis and Photophysical Characterization of Azoheteroarenes

A set of azoheteroarenes have been synthesized with Buchwald-Hartwig coupling and microwave-assisted O2oxidation as the key steps. Several compounds exhibit good to excellent photoswitching properties (high switching efficiency, good fatigue resistance, and thermal stability of Z-isomer) relevant for photocontrolled applications, which pave the way for use in photopharmacology

Characterization of Multiple Ion Channels in Cultured Human Cardiac Fibroblasts

Background: Although fibroblast-to-myocyte electrical coupling is experimentally suggested, electrophysiology of cardiac fibroblasts is not as well established as contractile cardiac myocytes. The present study was therefore designed to characterize ion channels in cultured human cardiac fibroblasts. Methods and Findings: A whole-cell patch voltage clamp technique and RT-PCR were employed to determine ion channels expression and their molecular identities. We found that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts. These include a big conductance Ca2+-activated K+ current (BKCa) in most (88%) human cardiac fibroblasts, a delayed rectifier K+ current (IKDR) and a transient outward K+ current (Ito) in a small population (15 and 14%, respectively) of cells, an inwardly-rectifying K+ current (IKir) in 24% of cells, and a chloride current (ICl) in 7% of cells under isotonic conditions. In addition, two types of voltage-gated Na+ currents (INa) with distinct properties were present in most (61%) human cardiac fibroblasts. One was a slowly inactivated current with a persistent component, sensitive to tetrodotoxin (TTX) inhibition (INa.TTX, IC50 = 7.8 nM), the other was a rapidly inactivated current, relatively resistant to TTX (INa.TTXR, IC50 = 1.8 μM). RT-PCR revealed the molecular identities (mRNAs) of these ion channels in human cardiac fibroblasts, including KCa.1.1 (responsible for BKCa), Kv1.5, Kv1.6 (responsible for IKDR), Kv4.2, Kv4.3 (responsible for Ito), Kir2.1, Kir2.3 (for IKir), Clnc3 (for ICl), NaV1.2, NaV1.3, NaV1.6, NaV1.7 (for INa.TTX), and NaV1.5 (for INa.TTXR). Conclusions: These results provide the first information that multiple ion channels are present in cultured human cardiac fibroblasts, and suggest the potential contribution of these ion channels to fibroblast-myocytes electrical coupling. © 2009 Li et al.published_or_final_versio