Intracellular Dynamics-Resolved Label-Free Scattering Reveals Real-Time Metabolism of Single Bacteria.

Nanoscopic investigation of bacterial cells is essential to reveal their physiological status, impacting all cellular functions. Currently, this requires labeled probes or targeted staining procedures. Herein, we report a new bacterial feature, intracellular dynamics-resolved Rayleigh scattering (IDRS), that visualizes spatiotemporal cytoplasmic transitions in unlabeled bacteria and characterizes their real-time physiological status in 10 s. From single-bacterium IDRS signals, we discovered unique spatial patterns and their multiple transitions in Gram-negative and Gram-positive bacteria. The magnitude of IDRS signal variation highly correlated with the metabolic status of bacteria, differentiating persistent subpopulations. This is also the first report demonstrating distinct real-time metabolic conditions of unlabeled drug-resistant bacteria that are exposed to different doses of antibiotics. Our strategy opens up a way to simultaneously trace in situ metabolic and antibiotic resistance statuses, which can be applied in single-cell level control of bacterial metabolism and efficacy with a heterogeneous nature.

Enhancing Diagnosis of Rotating Elements in Roll-to-Roll Manufacturing Systems through Feature Selection Approach Considering Overlapping Data Density and Distance Analysis.

Roll-to-roll manufacturing systems have been widely adopted for their cost-effectiveness, eco-friendliness, and mass-production capabilities, utilizing thin and flexible substrates. However, in these systems, defects in the rotating components such as the rollers and bearings can result in severe defects in the functional layers. Therefore, the development of an intelligent diagnostic model is crucial for effectively identifying these rotating component defects. In this study, a quantitative feature-selection method, feature partial density, to develop high-efficiency diagnostic models was proposed. The feature combinations extracted from the measured signals were evaluated based on the partial density, which is the density of the remaining data excluding the highest class in overlapping regions and the Mahalanobis distance by class to assess the classification performance of the models. The validity of the proposed algorithm was verified through the construction of ranked model groups and comparison with existing feature-selection methods. The high-ranking group selected by the algorithm outperformed the other groups in terms of training time, accuracy, and positive predictive value. Moreover, the top feature combination demonstrated superior performance across all indicators compared to existing methods.

Tool-Condition Diagnosis Model with Shock-Sharpening Algorithm for Drilling Process.

Fault diagnosis systems are used to improve the productivity and reduce the costs of the manufacturing process. However, the feature variables in existing systems are extracted based on the classification performance of the final model, thereby limiting their applications to models with different conditions. This paper proposes an algorithm to improve the characteristics of feature variables by considering the cutting conditions. Regardless of the frequency band, the noise of the measurement data was reduced through an oversampling method, setting a window length through a cutter sampling frequency, and improving its sensitivity to shock signal. An experiment was subsequently performed to confirm the performance of the model. Using normal and wear tools on AI7075 and SM45C, the diagnosis accuracies were 97.1% and 95.6%, respectively, with a reduction of 85% and 83%, respectively, in the time required to develop a diagnosis model. Therefore, the proposed algorithm reduced the model computation time and developed a model with high accuracy by enhancing the characteristics of the feature variable. The results of this study can contribute significantly to the establishment of a high-precision monitoring system for various processing processes.

Plasmonic Nanogap-Enhanced Raman Scattering with Nanoparticles.

Plasmonic coupling-based electromagnetic field localization and enhancement are becoming increasingly important in chemistry, nanoscience, materials science, physics, and engineering over the past decade, generating a number of new concepts and applications. Among the plasmonically coupled nanostructures, metal nanostructures with nanogaps have been of special interest due to their ultrastrong electromagnetic fields and controllable optical properties that can be useful for a variety of signal enhancements such as surface-enhanced Raman scattering (SERS). The Raman scattering process is highly inefficient, with a very small cross-section, and Raman signals are often poorly reproducible, meaning that very strong, controllable SERS is needed to obtain reliable Raman signals with metallic nanostructures and thus open up new avenues for a variety of Raman-based applications. More specifically, plasmonically coupled metallic nanostructures with ultrasmall (∼1 nm or smaller) nanogaps can generate very strong and tunable electromagnetic fields that can generate strong SERS signals from Raman dyes in the gap, and plasmonic nanogap-enhanced Raman scattering can be defined as Raman signal enhancement from plasmonic nanogap particles with ∼1 nm gaps. However, these promising nanostructures with extraordinarily strong optical signals have shown limited use for practical applications, largely due to the lack of design principles, high-yield synthetic strategies with nanometer-level structural control and reproducibility, and systematic, reliable single-molecule/single-particle-level studies on their optical properties. All these are extremely important challenges because even small changes (<1 nm) in the structure of the coupled plasmonic nanogaps can significantly affect the plasmon mode and signal intensity. In this Account, we examine and summarize recent breakthroughs and advances in plasmonic nanogap-enhanced Raman scattering with metal nanogap particles with respect to the design and synthesis of plasmonic nanogap structures, as well as ultrasensitive and quantitative Raman signal detection using these structures. The applications and prospects of plasmonic nanogap particle-based SERS are also discussed. In particular, reliable synthetic and measurement strategies for plasmonically coupled nanostructures with ∼1 nm gap, in which both the nanogap size and the position of a Raman-active molecule in the gap can be controlled with nanometer/sub-nanometer-level precision, can address important issues regarding the synthesis and optical properties of plasmonic nanostructures, including structural and signal reproducibility. Further, single-molecule/single-particle-level studies on the plasmonic properties of these nanogap structures revealed that these particles can generate ultrastrong, quantifiable Raman signals in a highly reproducible manner.

Quantitative Plasmon Mode and Surface-Enhanced Raman Scattering Analyses of Strongly Coupled Plasmonic Nanotrimers with Diverse Geometries.

Here, we quantitatively monitored and analyzed the spectral redistributions of the coupled plasmonic modes of trimeric Au nanostructures with two ∼1 nm interparticle gaps and single-dye-labeled DNA in each gap as a function of varying trimer symmetries. Our precise Mie scattering measurement with the laser-scanning-assisted dark-field microscopy allows for individual visualization of the orientations of the radiation fields of the coupled plasmon modes of the trimers and analyzing the magnitude and direction of the surface-enhanced Raman scattering (SERS) signals from the individual plasmonic trimers. We found that the geometric transition from acute-angled trimer to linear trimer induces the red shift of the longitudinally polarized mode and the blue shift of the axially polarized mode. The finite element method (FEM) calculation results show the distinct "on" and "off" of the plasmonic modes at the two gaps of the trimer. Importantly, the single-molecule-level systematic correlation studies among the near-field, far-field, and surface-enhanced Raman scattering reveal that the SERS signals from the trimers are determined by the largely excited coupled plasmon between the two competing plasmon modes, longitudinal and axial modes. Further, the FEM calculation revealed that even 0.5 nm or smaller discrepancy in the sizes of two gaps of the linear trimer led to >10-fold difference in the SERS signal. Granted that two gap sizes are not likely to be completely the same in actual experiments, one of two gaps plays a more significant role in generating the SERS signal. Overall, this work provides the knowledge and handles for the understanding and systematic control of the magnitude and polarization direction of the both plasmonic response and SERS signal from trimeric nanostructures and sets up the platform for the optical properties and the applications of plasmonically coupled trimers and higher multimeric nanostructures.

Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers.

BACKGROUND AND OBJECTIVES: Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), c.3435C>T (rs1045642)] and CYP3A5*3 (6986A>G) (rs776746) polymorphisms on the pharmacokinetics of quetiapine in humans. MATERIALS AND METHODS: Forty healthy male individuals were enrolled, and their ABCB1 and CYP3A5 polymorphisms were assessed. After a single dose of 100 mg quetiapine was administered, plasma concentrations of quetiapine were measured for 24 h and pharmacokinetic analysis was carried out. RESULTS: The ABCB1 polymorphisms including c.1236C>T, c.2677G>T/A, and c.3435C>>T did not affect plasma levels of quetiapine, and its pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the CYP3A5*3 polymorphism significantly affected the plasma level of quetiapine and its pharmacokinetics. The peak plasma concentration of quetiapine was 208.39 ng/ml for CYP3A5*1/*1, 243.46 ng/ml for CYP3A5*1/*3, and 332.94 ng/ml for CYP3A5*3/*3 (P=0.0118). The mean AUC(inf) (area under the time vs. concentration curve from 0 to infinity) value was 627.3, 712.77, and 1045.29 ng h/ml, respectively (P=0.0017). CONCLUSION: The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug.

Multiplex pyrosequencing method to determine CYP2C9*3, VKORC1*2, and CYP4F2*3 polymorphisms simultaneously: its application to a Korean population and comparisons with other ethnic groups.

Warfarin is an anticoagulant that is difficult to administer because of the wide variation in dose requirements to achieve a therapeutic effect. CYP2C9, VKROC1, and CYP4F2 play important roles in warfarin metabolism, and their genetic polymorphisms are related to the variability in dose determination. In this study we describe a new multiplex pyrosequencing method to identify CYP2C9*3 (rs1057910), VKORC1*2 (rs9923231), and CYP4F2*3 (rs2108661) simultaneously. A multiplex pyrosequencing method to simultaneously detect CYP2C9*3, VKORC1*2, and CYP4F2*3 alleles was designed. We assessed the allele frequencies of the polymorphisms in 250 Korean subjects using the multiplex pyrosequencing method. The results showed 100 % concordance between single and multiplex pyrosequencing methods, and the polymorphisms identified by pyrosequencing were also validated with the direct sequencing method. The allele frequencies of these polymorphisms in this population were as follows: 0.040 for CYP2C9*3, 0.918 for VKORC1*2, and 0.416 for CYP4F2*3. Although the allele frequencies of the CYP2C9*3 and VKROC1*2 were comparable to those in Japanese and Chinese populations, their frequencies in this Korean population differed from those in other ethnic groups; the CYP4F2*3 frequency was the highest among other ethnic populations including Chinese and Japanese populations. The pyrosequencing methods developed were rapid and reliable for detecting CYP2C9*3, VKORC1*2, and CYP4F2*3. Large ethnic differences in the frequency of these genetic polymorphisms were noted among ethnic groups. CYP4F2*3 exhibited its highest allele frequency among other ethnic populations compared to that in a Korean population.

Single-molecule and single-particle-based correlation studies between localized surface plasmons of dimeric nanostructures with ~1 nm gap and surface-enhanced Raman scattering.

Understanding the detailed electromagnetic field distribution inside a plasmonically coupled nanostructure, especially for structures with ~ 1 nm plasmonic gap, is the fundamental basis for the control and use of the strong optical properties of plasmonic nanostructures. Using a multistep AFM tip-matching strategy that enables us to gain the optical spectra with the optimal signal-to-noise ratio as well as high reliability in correlation measurement between localized surface plasmon (LSP) and surface-enhanced Raman scattering (SERS), the coupled longitudinal dipolar and high-order multipolar LSPs were detected within a dimeric structure, where a single Raman dye is located via a single-DNA hybridization between two differently sized Au-Ag core-shell particles. On the basis of the characterization of each LSP component, the distinct phase differences, attributed to different quantities of the excited quadrupolar LSPs, between the transverse and longitudinal regimes were observed for the first time. By assessing the relative ratio of dipolar and quadrupolar LSPs, we found that these LSPs of the dimer with ~ 1 nm gap were simultaneously excited, and large longitudinal bonding dipolar LSP/longitudinal bonding quadrupolar LSP value is required to generate high SERS signal intensity. Interestingly, a minor population of the examined dimers exhibited strong SERS intensities along not only the dimer axis but also the direction that arises from the interaction between the coupled transverse dipolar and longitudinal bonding quadrupolar LSPs. Overall, our high-precision correlation measurement strategy with a plasmonic heterodimer with ~ 1 nm gap allows for the observation of the characteristic spectral features with the optimal signal-to-noise ratio and the subpopulation of plasmonic dimers with a distinct SERS behavior, hidden by a majority of dimer population, and the method and results can be useful in understanding the whole distribution of SERS enhancement factor values and designing plasmonic nanoantenna structures.

SLCO2B1 genetic polymorphisms in a Korean population: pyrosequencing analyses and comprehensive comparison with other populations.

SLCO2B1, also known as OATP2B1 (Organic Anion Transporter) or OATP-B or SLC21A9, is an organic anion uptake transporter that is encoded by the SLCO2B1 gene. In this study we assessed the frequencies of SLCO2B1 polymorphisms in a Korean population using newly developed pyrosequencing methods and compared their frequencies with those in other ethnic groups. We developed pyrosequencing methods to identify the following six SLCO2B1 non-synonymous polymorphisms: c.1175C > T (rs1621378), c.1457C > T (rs2306168), c.43C > T (rs56837383), c.935G > A (rs12422149), c.601G > A (rs35199625) and c.644A > T (rs72559740). The allele frequencies of these polymorphisms were analyzed in 227 Korean subjects. The allele frequencies of SLCO2B1 polymorphisms in the population tested were as follows: 0.0 for c.1175C > T, c.43C > T and c.644A > T; 0.2687 for c.1457C > T; 0.4273 for c.935G > A; and 0.0727 for c. 601G > A. Even though the allele frequencies of the c.1175C > T and c.1457C > T polymorphisms were comparable to those in Japanese subjects, the frequencies in this Korean population differed from those in other ethnic groups. The developed pyrosequencing methods are rapid and reliable for detecting non-synonymous SLCO2B1 polymorphisms. Large ethnic differences in the frequency of SLCO2B1 genetic polymorphisms were noted among ethnic groups. The SLCO2B1 polymorphisms at c.1175C > T, c.43C > T and c.644A > T were not found in the Korean population while c.1457C > T, c.935G > A and c.601G > A exhibited mostly higher frequencies in Koreans compared with Finnish, Caucasian and African-American populations.

Nanotube-bridged wires with sub-10 nm gaps.

We report a simple but efficient method to synthesize carbon nanotube-bridged wires (NBWs) with gaps as small as 5 nm. In this method, we have combined a strategy for assembling carbon nanotubes (CNTs) inside anodized aluminum oxide pores and the on-wire lithography technique to fabricate CNT-bridged wires with gap sizes deliberately tailored over the 5-600 nm range. As a proof-of-concept demonstration of the utility of this architecture, we have prepared NBW-based chemical and biosensors which exhibit higher analyte sensitivity (lower limits of detection) than those based on planar CNT networks. This observation is attributed to a greater surface-to-volume ratio of CNTs in the NBWs than those in the planar CNT devices. Because of the ease of synthesis and high yield of NBWs, this technique may enable the further incorporation of CNT-based architectures into various nanoelectronic and sensor platforms.

Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2.

Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified. Structure-and-activity and structure-and-toxicity relationship studies demonstrated that compounds 2e and 2h were most potent against influenza A and B viruses but minimally cytotoxic. It is noteworthy that in contrast to cytotoxic gemcitabine, they inhibited viral infection with 90% effective concentrations of 14.5-34.3 and 11.4-15.9 µM, respectively, maintaining viability of mock-infected cells over 90% at 300 µM. Resulting antiviral selectivity was comparable to that of a clinically approved nucleoside analogue, favipiravir. The cell-based viral polymerase assay proved the mode-of-action of 2e and 2h targeting viral RNA replication and/or transcription. In a murine influenza A virus-infection model, intraperitoneal administration of 2h not only reduced viral RNA level in the lungs but also alleviated infection-mediated pulmonary infiltrates. In addition, it inhibited replication of severe acute respiratory syndrome virus 2 infection in human lung cells at subtoxic concentrations. The present study could provide a medicinal chemistry framework for the synthesis of a new class of viral polymerase inhibitors.

Concurrent Imaging of Surface-Enhanced Raman and Mie Scattering from Built-in Nanogap Plasmonic Particles.

We report a bimodal imaging method that can spatially resolve and concurrently correlate SERS and background-free Mie scattering signals. By examining two types of nanoparticle assemblies with different types of plasmonic junctions, namely raspberry-like metamolecules (raspberry-MMs) containing intraparticle nanogaps and groups of Au nanocubes forming interparticle gaps, we were able to rapidly screen SERS-active particles among the entire population of nanoparticles. Ratiometric analysis of SERS/Mie scattering revealed distinct behaviors for these intra- and interparticle nanogaps. In particular, raspberry-MMs showed a high fraction of SERS-active particles with the SERS intensity essentially insensitive to the nanoparticle aggregation state and a predictable environmental dependence. In comparison, nanocube clusters exhibited highly heterogeneous SERS/Mie scattering ratios and unpredictable intensity fluctuations but higher maximum SERS intensity. This dual-imaging approach constitutes an in situ visualization tool that enables simultaneous and stoichiometric analysis of dual signals consisting of elastic and inelastic scattering, which can significantly improve the reliability of SERS measurements.

Discrimination between target and non-target interactions on the viral surface by merging fluorescence emission into Rayleigh scattering.

Direct and quantitative determination of antibodies or cellular receptors dynamically binding to the surface of viral particles is the key issue for predicting the efficacy of therapeutic materials or host susceptibility to a new emerging pathogen. However, targeted visualization of infectious viruses is still highly challenging owing to their nanoscopic sizes and uncontrollable nonspecific interactions with loading molecules responsible for false signals. Here we present a multimodal single-molecule and single-particle (SMSP) visualization capable of simultaneously yet independently tracking Rayleigh scattering and fluorescence that, respectively, are generated from viruses (approximately 100 nm) and labeled interacting molecules. By analyzing real-time trajectories of fluorescent antibodies against a virus surface protein with reference to single virus-derived Rayleigh scattering, we determined heterogeneous binding stoichiometry of virus-antibody couplings irrespective of the nonspecific binder population. Therefore, our multimodal (or multi-level) SMSP assay visually identifies and selectively quantifies specific interactions between them with single binding event accuracy. As a 'specific-binding quantifier' to assess variable host susceptibility to a virus, it was further applied for distinguishing ratiometric bindings and spontaneous dissociation kinetics of synthesized isomeric receptors to influenza virus. The present framework could offer a solid analytical foundation for the development of a direct-acting antiviral agent inhibiting an integral viral enveloped protein and for nanobiological investigation for dissecting spatiotemporal nanoparticle-molecule interactions, which have been scarcely explored compared to those among plasmonic nanoparticles or among molecules only.

S1219 residue of 53BP1 is phosphorylated by ATM kinase upon DNA damage and required for proper execution of DNA damage response.

53BP1 is phosphorylated by the protein kinase ATM upon DNA damage. Even though several ATM phosphorylation sites in 53BP1 have been reported, those sites have little functional implications in the DNA damage response. Here, we show that ATM phosphorylates the S1219 residue of 53BP1 in vitro and that the residue is phosphorylated in cells exposed to ionizing radiation (IR). Transfection with siRNA targeting ATM abolished IR-induced phosphorylation at this residue, supporting the theory that this process is mediated by the kinase. To determine the functional relevance of this phosphorylation event, a U2OS cell line expressing S1219A mutant 53BP1 was established. IR-induced foci formation of MDC1 and gammaH2AX, DNA damage signaling molecules, was reduced in this cell line, implying that S1219 phosphorylation is required for recruitment of these molecules to DNA damage sites. Furthermore, overexpression of the mutant protein impeded IR-induced G2 arrest. In conclusion, we have shown that S1219 phosphorylation by ATM is required for proper execution of DNA damage response.

Epidural Nerve Blocks Increase Intraoperative Vasopressor Consumption and Delay Surgical Start Time in Deep Inferior Epigastric Perforator Free Flap Breast Reconstruction.

BACKGROUND: Epidural nerve blocks (EA) have been widely used in abdominal and thoracic surgery as an adjunct to general anesthesia (GA). The role for EA in microsurgical free flap breast reconstruction remains unclear with concerns regarding its impact on flap survival and operating room efficiency. The purpose of this study was to examine the effectiveness of epidural blocks in patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: A retrospective analysis of patients undergoing DIEP breast reconstruction under GA alone was compared with those receiving EA/GA. Electronic records were analyzed for patient demographics, intraoperative data, and postoperative outcomes. The primary outcome was 48-hour narcotic usage and secondary outcomes were intraoperative vasopressor consumption, surgical delay, and safety profile. RESULTS: Sixty-one patients underwent DIEP reconstruction, 46 (75%) underwent EA/GA and 15 (25%) underwent GA alone. Epidural blocks were associated with a significant delay in operating room start time (67.8 min versus 45.6 min; P = 0.0004.) Patients in the EA/GA group also had a significant increase in vasopressor use (n = 38 versus n = 8; P = 0.037); however, there was no difference in flap complication rate [1 (2%) versus 2 (13%); P = 0.15]. Postoperatively, patients who received an epidural block had a reduced average pain score (1.1 versus 2.2; P = 0.0235), but there was no difference in 48-hour narcotic usage. CONCLUSIONS: Although epidural blocks reduce postoperative pain following DIEP flap breast reconstruction, they increase intraoperative vasopressor use and delay the start time of the case. Further studies are required to elucidate whether the benefits of improved pain control outweigh the potential risk for increased surgical complications and increased health care costs.

Fabrication and near-field visualization of a wafer-scale dense plasmonic nanostructured array.

Developing a sensor that identifies and quantifies trace amounts of analyte molecules is crucially important for widespread applications, especially in the areas of chemical and biological detection. By non-invasively identifying the vibrational signatures of the target molecules, surface-enhanced Raman scattering (SERS) has been widely employed as a tool for molecular detection. Here, we report on the reproducible fabrication of wafer-scale dense SERS arrays and single-nanogap level near-field imaging of these dense arrays under ambient conditions. Plasmonic nanogaps densely populated the spaces among globular Ag nanoparticles with an areal density of 120 particles per µm2 upon application of a nanolithography-free simple process consisting of the Ar plasma treatment of a polyethylene terephthalate substrate and subsequent Ag sputter deposition. The compact nanogaps produced a high SERS enhancement factor of 3.3 × 107 and homogeneous (coefficient of variation of 8.1%) SERS response. The local near fields at these nanogaps were visualized using photo-induced force microscopy that simultaneously enabled near-field excitation and near-field force detection under ambient conditions. A high spatial resolution of 3.1 nm was achieved. Taken together, the generation of a large-area SERS array with dense plasmonic nanogaps and the subsequent single-nanogap level characterization of the local near field have profound implications in the nanoplasmonic imaging and sensing applications.

Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells.

Taurine-induced changes in the expression profiles of HepG2 cells were assessed using a cDNA microarray technology, and confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. Of 8,298 human genes on the microarray, 128 genes (87 known genes) were up-regulated, and 349 (206 known genes) were down-regulated more than 2.0-fold by taurine. Among the 293 known genes regulated by taurine, a total of 44 genes were involved in signal transduction; 16 genes were up-regulated greater than 2.0-fold, and 28 genes were down-regulated more than 2.0-fold by taurine. The results of RT-PCR analyses for the five genes selected were consistent with our microarray data, although the fold changes in the expression level differed somewhat between the two analytical methods. Among signal transduction-related genes affected by taurine, four genes--mitogen-activated protein kinase (MAPK) kinase kinase 7, p21-activated kinase 4, sprouty homolog 2, and MAPK kinase 1--are implicated in the MAPK signaling pathway. Taurine also regulated the expression of signal transducer and activator of transcription (STAT) 3 gene involved in the Janus kinase-STAT pathway, and diacylglycerol kinase, zeta 104 kDa, the downstream mediator of the protein kinase C transmembrane signaling pathway. In conclusion, gene expression profiling of HepG2 cells treated with taurine provided us with new insights into the novel aspects of taurine as a possible regulator of MAPK signaling cascades and protein kinase C signaling pathways involved in cellular processes such as cell growth, differentiation, and apoptosis.

Effects of different dosages of oxycodone and fentanyl on the hemodynamic changes during intubation.

OBJECTIVES: To investigate the effectiveness of oxycodone compared with fentanyl for attenuating the hemodynamic response during endotracheal intubation. METHODS: This study was conducted from June 2014 to February 2015 on healthy adults undergoing general anesthesia at the Yeungnam University Hospital, Daegu, Republic of Korea. Ninety-five patients were randomly assigned to one of 3 groups to receive the following drugs; Group F: fentanyl 2 µg/kg; Group O/70: oxycodone 140 µg/kg; Group O/100: oxycodone 200 µg/kg. Five minutes after injection of the study drug, general anesthesia was induced with propofol 1.5 mg/kg and rocuronium 0.8 mg/kg. The mean blood pressure (MBP), heart rate (HR), peripheral oxygen saturation (SpO2), and bispectral index (BIS) were compared before administration of the study drug (T1), just before endotracheal intubation (T2), one minute after endotracheal intubation (T3), and 7.5 minutes after endotracheal intubation (T4). Complications were assessed. RESULTS: The 2 oxycodone groups showed no significant differences in MBP, HR, SpO2, and BIS compared to Group F at the time points assessed. The incidence of complications was comparable among the groups.  CONCLUSIONS: Oxycodone could successfully be used to attenuate the sympathetic response during anesthetic induction. The hemodynamic profiles and incidence of complications were clinically similar among the groups, but Group O/70 tended to show a lower rate of complications of apnea.

Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans.

BACKGROUNDS: Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer. Drug transporters P-glycoprotein encoded by ABCB1 and breast cancer resistance protein (BCRP) encoded by ABCG2 are involved in the transportation of bicalutamide and its treatment failure. We evaluated the roles of ABCB1 and ABCG2 genetic polymorphisms in the pharmacokinetics of bicalutamide in humans. METHODS: After a single oral dose of 150mg bicalutamide was administered, plasma concentrations of bicalutamide were measured, and pharmacokinetic analyses were performed in 27 healthy subjects according to ABCB1 (c.1236C>T, c.2677G>T/A, and c.3435C>T) and ABCG2 (c.34G>A and c.421C>A). RESULTS: ABCB1 polymorphisms did not affect the plasma levels of bicalutamide and the pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the ABCG2 c.421C>A polymorphism significantly influenced the plasma levels and pharmacokinetics of bicalutamide gene dose-dependently. CONCLUSIONS: The ABCB1 genetic polymorphisms did not influence the pharmacokinetics of bicalutamide. However, ABCG2 c.421C>A significantly and gene dose-dependently influenced its pharmacokinetics, but c.34G>A did not.

Cortisol and IGF-1 synergistically up-regulate taurine transport by the rat skeletal muscle cell line, L6.

This study was undertaken to evaluate effects of exercise-induced hormones, cortisol, IGF-1, and beta-endorphin, on the regulation of taurine transport activity in rat skeletal myoblasts, L6 cells. Challenge of L6 cells with cortisol (100 nM) for 24 hrs resulted in a 165% increase in taurine transport activity, 220% increase in Vmax of the taurine transporter, and 55% increase in taurine transporter/ beta-actin mRNA level compared with untreated control cells. Neither IGF-1 (1 approximately 100 nM) nor beta-endorphin (1 approximately 20 nM), added in the incubation medium separately for 24 hrs, affected taurine uptake by L6 cells. However, when cells were co-treated with IGF-1 (10 nM) plus cortisol (100 nM), taurine transport activity (37% increase, p < 0.05), Vmax of the transporter (54%, p < 0.05), and taurine transporter/ beta-actin mRNA level were further increased compared to the value for cells treated with cortisol alone. These results suggest that taurine transport by skeletal muscle cells appear to be synergistically up-regulated during a prolonged exercise via elevated levels of cortisol and IGF-1 in muscle.