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Background/Aims To investigate an effect of ML204 (an inhibitor of transient receptor potential canonical 4 and 5 [TRPC4/5] channels) on interstitial cells of Cajal (ICCs) and therefore determine whether TRPC4/5 channels act on ICC-generated pacemaker activity. Methods We enforced whole cell patch clamp analysis, measurements of the intracellular Ca2+ concentration, and reverse transcription polymerase chain reaction to determine the effect of ML204 (10 μM) or englerin A (a selective activator of TRPC4/5 channeles, 10 μM) and the existence of TRPC4/5 in mouse small intestinal ICC. Results Treatment of ICCs with ML204 or englerin A caused the membrane potentials to depolarize. This depolarization effect of membrane potentials by ML204 in ICCs was observed to be concentration-dependent. After treating Ca2+- and Na+-free solutions or flufenamic acid (a non-selective cation channel blocker), the pacemaker potentials in the ICCs were abolished. A specific anoctamin 1 channel blocker did not have any effect on the pacemaker activity in ML204-untreated control cells; however, they blocked ML204-induced pacemaker activity in ICCs. Specific primers designed against TRPC4 and TRPC5 detected the presence of TRPC4/5 in small intestinal ICCs, and the application of ML204 increased raise the frequency of Ca2+ oscillations in ICCs, as assessed using Fluo-4 AM. Conclusion The results implied that ML204 could not inhibit the pacemaker activity but depolarized the membrane potential of ICCs by regulating intracellular Ca2+ oscillations and anoctamin 1 channels. [ABSTRACT FROM AUTHOR]

We theoretically propose a method based on the combination of a nonlinear optical mass sensor using a hybrid spin-microcantilever and the nanoparticle-enhanced technique, to detect and monitor DNA mutations. The technique theoretically allows the mass of external particles (ssDNA) landing on the surface of a hybrid spin-microcantilever to be detected directly and accurately at 300 K with a mass responsivity 0.137 Hz/ag in situ in liquid. Moreover, combined with the nanoparticle-enhanced technique, even only one base pair mutation in the target DNA sequence can be identified in real time accurately, and the DNA hybridization reactions can be monitored quantitatively. Furthermore, in situ detection in liquid and measurement of the proposed nonlinear optical spin resonance spectra will minimize the experimental errors. [ABSTRACT FROM AUTHOR]

Effects of geometric structure parameters of 10 mm-diameter hydrocyclones on the particle separation efficiency are studied using computational fluid dynamics (CFD). The fluid velocity profiles and particle trajectories are simulated using RFLOW software with a standard isotropic k-ε turbulent model. The JIS standard CaCO3-17 particles are adopted as a particulate sample in simulations and experiments. Comparing the simulated results with experimental data, a maximum deviation about 20% in partition curves occurs for 5-10 µm particles. However, fairly good agreements for the cut-size predictions and the fish-hook phenomenon are obtained. The simulated cut-size d50 is only 2 µm larger than that measured in experiments, while the value of d100 can be accurately predicted. An increase in overflow diameter or a decrease in underflow diameter leads to a lower separation efficiency but a clearer separation sharpness due to lower fluid underflow rate. A short-and-wide rectangular inlet is more efficient for particle separation than a tall-and-narrow one. An inclined inlet conduit plays an inessential role on the efficiency improvement but gains a 2 µm reduction in d100. Comparing the simulated results, the hydrocyclone used in the experiments of this study exhibits a higher separation sharpness than the Rietema type and a higher efficiency than the Bradley type based on the same operation capacity and hydrocyclone size. [ABSTRACT FROM AUTHOR]

The use of a high k composite dielectric composed of La2O3 and HfO2 layers as the gate dielectric for In0.53Ga0.47As MOS application is proposed. Two multi-layer structures of La2O3 (1 nm)/HfO2 (1 nm) and La2O3 (0.5 nm)/HfO2 (0.5 nm) were deposited and annealed at 450 and 500°C for device performance comparison. X-ray photoelectron spectroscopy, TEM and C-V measurements were used for the interface analysis between the oxide and the semiconductor. Finally, a 1 nm equivalent-oxide-thickness dielectric with small hysteresis of 88 mV and Dit of 1.9 × 1012 cm-2 eV-1 was achieved for six layers of an La2O3 (0.5 nm)/HfO2 (0.5 nm) composite oxide structure on an In0.53Ga0.47As MOS capacitor with a post-deposition annealing temperature of 450°C. [ABSTRACT FROM AUTHOR]

Motivated by recent experimental progress towards the detection and manipulation of Majorana fermions in ferromagnetic atomic chains on a superconductor, we present a novel proposal based on a single-crystal diamond (SCD) microcantilever with a single nitrogen-vacancy (NV) center spin embedded in ultrapure diamond substrate to probe Majorana fermions in an all-optical domain. With this scheme, a possible distinct Majorana signature is investigated via the electron spin resonance spectrum. In the proposal, the SCD microcantilever behaves as a phonon cavity and is robust for detecting of Majorana fermions, while the NV center spin can be considered as a sensitive probe. Further, the vibration of the microcantilever will enhance the coupling effect, which makes the Majorana fermions more sensitive to detection and the well-established optical NV spin readout technology will certainly promote the detection. This proposed method may provide a potential supplement for the detection of Majorana fermions. [ABSTRACT FROM AUTHOR]

Nowadays hybrid spin-micro/nanomechanical systems are being actively explored for potential quantum sensing applications. In combination with the pump-probe technique or the spin resonance spectrum, we theoretically propose a realistic, feasible, and an exact way to measure the cantilever frequency in a hybrid spin-micromechanical cantilever system which has a strong coherent coupling of a single nitrogen vacancy center in the single-crystal diamond cantilever with the microcantilever. The probe absorption spectrum which exhibits new features such as mechanically induced three-photon resonance and ac Stark effect is obtained. Simultaneously, we further develop this hybrid spin-micromechanical system to be an ultrasensitive mass sensor, which can be operated at 300 K with a mass responsivity 0.137 Hz ag−1, for accurate sensing of gaseous or aqueous environments, chemical vapors, and biomolecules. And the best performance on the minimum detectable mass can be in vacuum. Finally, we illustrate an in situ measurement to detect Angiopoietin-1, a marker of tumor angiogenesis, accurately with this hybrid microcantilever at room temperature. [ABSTRACT FROM AUTHOR]

Please cite this paper as: CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy. Experimental Dermatology 2010; 19: 246–251. Although immunotherapy is not accepted as a curative treatment for atopic dermatitis (AD), most studies have shown positive effects of immunotherapy on AD patients. The serum levels of CC chemokine ligand 17 (CCL17), CCL22 and CCL18 have been reported to be highly correlated with disease severity, which suggests important roles for CC chemokines in the pathogenesis of AD. Objective: The purpose of this study was to investigate the changes in clinical and immunologic markers before and after immunotherapy and to find which CC chemokines correlate with clinical improvement after immunotherapy with house dust mite (HDM) allergens in AD patients. Methods and Results: A total of 20 AD patients who were sensitized to HDM allergens through a skin-prick test and Pharmacia CAP system were treated with subcutaneous immunotherapy using HDM allergens (treatment duration 12–60 months). Eczema area and severity index scores in 20 patients with AD decreased significantly after immunotherapy ( P < 0.001). Serum total immunoglobulin E (IgE) and Dermatophagoides pteronyssinus-specific IgE levels tended to decrease after treatment although this was not statistically significant, and the D. farinae-specific IgE level showed no change. Serum CCL17, CCL22 and CCL18 levels decreased significantly from baseline after treatment ( P = 0.043, 0.017 and <0.001, respectively). The percentage reductions in serum CCL17 and CCL22 level were significantly correlated with reductions in disease severity ( P = 0.007, R2 = 0.301 and P = 0.037, R2 = 0.177, respectively). Conclusion: We suggest that CCL17 and CCL22 are good immunological marker candidates that can be used to assess clinical improvement after immunotherapy in AD patients. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic IL-23/Th17 pathway-associated skin disease. An increased expression of lesional CCL20 can recruit CCR6+ Th17, and lesional cytokine milieu persistently activates keratinocytes to produce CCL20. Lipid-lowering drugs, statins, are known to possess immune-modulating functions. In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL-1β, TNF-α, and IL-17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells towards CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells. [ABSTRACT FROM AUTHOR]

Background: Polydeoxyribonucleotide (PDRN) influencing cellular growth and differentiation is recognized to promote wound healing by stimulating tissue repair. Although PDRN can be extracted from human placentas, PDRN medications have recently been extracted from the semen of trout (Oncorhynchus mykiss) and salmon (Oncorhynchus keta). The present study was designed to evaluate the wound healing effects of O. keta -derived PDRN for injection (Rejuvenex) and PDRN cream (Rejuvenex Cream) in comparison with those of O. mykiss -derived PDRN injection (Placentex). Methods: Full-thickness skin defects were made on the back of mice (n=60). The mice were divided into the following four groups according to the dressing used for the wounds: O. mykiss -derived PDRN injection group, O. keta -derived PDRN injection group, O. keta - derived PDRN cream group, and normal saline soaked dressing group (control group). We analyzed the gross findings, wound sizes, histological findings, immunohistochemistry and enzyme-linked immunosorbent assays for the groups immediately after the treatment, and again after 4, 7, and 10 days of treatment. Results: The wound healing effects were the greatest in the O. keta -derived PDRN injection and O. mykiss -derived PDRN injection groups, which showed similar scores, followed by the O. keta -derived cream and normal saline soaked dressing groups. Conclusion: The injection of PDRN extracted from O. keta was found to be as effective at healing full-thickness skin defects as the O. mykiss -derived PDRN injection, which is currently used in the clinic. Moreover, the O. keta -derived PDRN injection was also found to reduce the time required for wound healing. [ABSTRACT FROM AUTHOR]

Children are more susceptible to medication errors because of differences in pharmacokinetics and pharmacodynamics compared to adults. Weight changes are common with growth in children and computer systems frequently are not updated with current information, which result in inaccurate weight-based dosing and thus harm children. This study evaluated the impact of a Computerized Physician Order Entry system with standardized pediatric dosing decision support (PDDS) function on reducing pediatric dosing errors. Outpatient prescriptions were analyzed from January to March during 2010 and 2011. The total number of pediatric prescriptions was 72,431 and 80,532 prior to and after system implementation, respectively. Out of 72,431 prescriptions, 1617 (2.23%) dosing errors were retrospectively detected by the system, whereas 15 dosing errors (0.02%) were detected by pharmacists prior to system implementation. Incorporating the system into practice resulted in a total of 210 successfully blocked dosing near misses, including 14 potentially fatal and 11 serious near misses. The final dosing error rate was significantly reduced from 2.23% to 0.66% ( p < 0.001). A 10-fold increase of the near miss correction rate (0.02% vs. 0.26%, p < 0.001) was observed. The Computerized Physician Order Entry system with standardized pediatric dosing decision support system provided real-time warning and significantly decreased the dose error rate among pediatric patients. [ABSTRACT FROM AUTHOR]

Psychological stress and atopic dermatitis (AD) symptoms appear to form a vicious cycle. This study compared the degree of stress and impairment of dermatology life quality between patients with AD and healthy controls, and examined for neuropeptides and neurotrophins associated with stress in AD. Questionnaires, comprising five tests evaluating depression, anxiety, interaction anxiousness, private body consciousness, and dermatology life quality, were examined in age- and sex-matched patients with AD (n=28) and healthy controls (n=28). Immunohistochemical staining of nerve growth factor, substance P, corticotrophin-releasing factor receptor and neuropeptide Y was performed in the AD-involved and normal skin. Patients with AD showed high scores on all of the questionnaires, including Beck Depression Inventory, state anxiety, trait anxiety, Interaction Anxiousness Scale, Private Both Consciousness subscale, and Dermatology Life Quality Index. All of the parameters, except for Beck Depression Inventory, showed higher values in AD than healthy controls (p<0.001). Statistically significant correlations were observed between each psychological parameter and Dermatology Life Quality Index. Among the clinical parameters, only pruritus was positively correlated with state anxiety (R=0.573,p<0.05) and trait anxiety (R=0.525,p<0.05). The Eczema Area and Severity Index score did not show any significant correlations with psychological parameters. Nerve growth factor-reactive cells were observed more abundantly and intensely in both epidermis and dermis of AD involved skin (n=4) than in healthy controls (n=3) (p=0.022 and 0.029, respectively). Also, the number and intensity of neuropeptide Y-positive cells was significantly greater in the entire epidermis of patients with AD than in healthy controls (n=3) (p0.029 and 0.026, respectively). We conclude that anxiety may be associated with the induction of pruritus through neuropeptide Y and nerve growth factor. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin-releasing factor (CRF), which activates the hypothalamo-pituitary-adrenal (HPA) axis under stress, also has pro-inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte-derived DC (MoDC) of atopic dermatitis patients and non-atopic healthy controls. In this study, mRNAs for CRF-R1α and 1β, as well as the CRF-R1 protein, were detected in MoDCs. CRF-R2α (but not R2β or R2γ) mRNA and the CRF-R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL-18 in both atopic dermatitis patients and non-atopic healthy controls. However, CRF did not alter the expression of IL-6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs. [ABSTRACT FROM AUTHOR]

Background: Although most patients with atopic dermatitis (AD) show high total and allergen-specific serum immunoglobulin E (IgE) levels, a small subgroup of AD patients have normal total IgE levels and negative serum allergen-specific IgE. This subgroup has been termed ‘intrinsic’ AD (IAD) as a counterpart to ‘extrinsic’ AD (EAD). However, the difference of chemokines between IAD and EAD has not yet been evaluated. Objective: We investigated the expression of CC chemokine ligand (CCL) 17, CCL22, and CCL18 in patients with IAD and EAD, which are known to be highly expressed in AD patients. Methods: We assessed the protein levels of these chemokines in peripheral blood mononuclear cells (PBMCs), sera and lesional skins. We also evaluated CCL18 mRNA levels in monocytes, Langerhans cell (LC)-like dendritic cells (DCs) and inflammatory dendritic epidermal cell (IDEC)-like DCs from both types of AD patients. Results: There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with IAD and EAD. CCL18 expression did not differ in PBMCs, sera and LC-like DCs from the two subgroups, but strong CCL18 expression was observed in lesional skins and IDEC-like DCs in patients with EAD. Lastly, serum CCL18 levels significantly decreased after immunotherapy. Conclusion: This study suggests that the chemokine micromilieu, especially the level of CCL18, is different between EAD and IAD patients. High FcεRI surface-expressing DCs, such as IDEC, were the major source of CCL18, and produced a prominent CCL18 microenvironment in EAD patients compared with IAD patients. [ABSTRACT FROM AUTHOR]