Fabrication and Evaluation of Ultrasound-Responsive Emulsion Loading Paclitaxel for Targeted Chemotherapy.

Chemotherapy is the most widely used cancer treatment, but it has several drawbacks such as adverse side effects and low bioavailability. To address these limitations, various drug delivery systems have been investigated, including liposomes, micelles, and emulsions. These drug delivery technologies have been improving the efficacy and safety of conventional chemotherapy. This study presents an emerging drug delivery technology for targeted chemotherapy using drug-loaded ultrasound-responsive emulsion (URE) as a drug carrier and ultrasound technology for external activation. URE was designed to be responsive to ultrasound energy and fabricated by using an emulsification technique. To investigate this technology, paclitaxel, as a model drug, was used and encapsulated into URE. The size distribution, morphology, and drug release behavior of paclitaxel-loaded URE (PTX-URE) were characterized, and the echogenicity of PTX-URE was assessed by using ultrasound imaging equipment. The cellular uptake and cytotoxicity of PTX-URE with ultrasound were evaluated in breast cancer cells (MDA-MB-231). Our in vitro results indicate that the combination of PTX-URE and ultrasound significantly enhanced cellular uptake by 10.6-fold and improved cytotoxicity by 24.1% compared to PTX alone. These findings suggest that the URE platform combined with ultrasound is a promising technology to improve the drug delivery efficiency for chemotherapy.

Design of a Brownian ratchet based on repetitive aggregation and dispersion of stimuli-responsive molecules.

We propose a Brownian ratchet for the unidirectional transport of stimuli-responsive molecules confined in a series of asymmetric geometries. It relies on repetitive cycles of aggregation and dispersion, which cause significant changes in molecular distribution within the confining geometry and enable the Brownian motion of the molecules to be ratcheted in a specific direction. To demonstrate the feasibility of the proposed Brownian ratchet, we conducted Brownian dynamics simulations where stimuli-responsive molecules were repeatedly aggregated and dispersed in a series of truncated conical tubes by altering intermolecular interactions. These simulations demonstrated the unidirectional transport of the molecules, indicating the efficacy of the proposed Brownian ratchet. Furthermore, we found that it becomes more effective with higher concentrations of molecules. This study suggests that, through the deliberate control of molecular assembly and disassembly by stimuli-responsive intermolecular interactions, it is possible to achieve directional and controlled molecular transport in various nanoscale applications.

Chronic Intestinal Inflammation Suppresses Brain Activity by Inducing Neuroinflammation in Mice.

Chronic gut inflammation such as inflammatory bowel disease is believed to be associated with neurodegenerative diseases in humans. However, the direct evidence for and the underlying mechanism of this brain-gut interaction remain elusive. In this study, manganese-enhanced magnetic resonance imaging was used to assess functional brain activity from awake and freely moving mice with chronic colitis. Manganese ion uptake (indicative of Ca2+ influx into neuronal cells) and accumulation were reduced in the hippocampus of chronic colitis mice compared with control mice. Long-term memory declined and neuroinflammatory signals, including IL-1ß production and activation of caspase-1, caspase-11, and gasdermin, were induced. High-mobility group box 1 (HMGB1) levels were elevated both in the serum and in the hippocampus; however, lipopolysaccharide (LPS) levels remained at low levels without significant changes in these samples. The blood-brain barrier permeability was increased in chronic colitis mice. In the presence of LPS, HMGB1 treatment induced the activation of caspase-11 and gasdermin in the mouse microglial cell line SIM-A9. These findings suggest that HMGB1 released from the inflamed intestine may move to the brain through the blood circulatory system; in conjunction with a low level of endogenous LPS, elevated HMGB1 can subsequently activate caspase-mediated inflammatory responses in the brain.

Dissolution Behavior of Fluoroalkylated Diazonaphthoquinone and Its Blends with Fluorinated Copolymers under UV Irradiation.

This article reports on the synthesis of materials containing both a fluoroalkyl group and a diazonaphthoquinone (DNQ) moiety as well as the fabrication of negative- and positive-tone stencil patterns. Additionally, the photoreaction mechanism that contributes to the pattern formation process is discussed, and the application of these materials is explored in the pixel-formation process in organic light-emitting diode (OLED) displays. Fluoroalkylated diazonaphthoquinone (RF2D1) was synthesized using chemically binding a DNQ unit, which can be converted into carboxylic acid derivatives having stronger polarity, with two fluorinated alkyl chains. The purified compound is found to be soluble in a nonpolar fluorous solvent and can be uniformly coated as a thin film. When the thin film of RF2D1 is exposed to 365 nm UV light, its solubility in a fluorous solvent decreases due to the Wolff rearrangement and subsequent hydrolysis of a ketene moiety. In contrast, when a mixture of RF2D1 and a hydrophobic, fluorinated copolymer is tested for the patterning process, the copolymer delays the conversion of the ketene intermediate to carboxylic acid, resulting in the dissolution of the exposed areas in the fluorous solvent. Finally, the applicability of these materials in micropatterning is demonstrated by adopting them in the orthogonal photolithography process to create pixels of OLEDs.

Percutaneous Bone-Anchored Hearing Implant: Is It Clinically Useful in Korean?

BACKGROUND: The aim of this study is to investigate the clinical effectiveness of Ponto in Korea, a recently released percutaneous bone-anchored hearing implant. METHODS: 16 patients with single-sided deafness (SSD) and mixed or conductive hearing loss who underwent Ponto implantation from December 2018 to September 2020 were enrolled in the study. Puretone audiometry, the Korean version of the Hearing in Noise Test (K-HINT), sound localization test (SLT), and Pupillometry were performed pre- and three months post-operation. Standardized questionnaires, the Hearing Handicap Inventory for the Elderly (HHIE) and Speech, Spatial and Qualities of Hearing Scale (SSQ), were administered. RESULTS: The mean age of subjects was 55.5 (range, 48-67) years. Four males and 12 females participated in the study. The mean puretone average was 73.17 dB hearing level (HL) before surgery and significantly improved to 36.72 dB HL three months after surgery. The mean word recognition score improved from 26.0% to 90.75% after implantation. In the case of K-HINT, there was a significant difference in summation (Z = -2.250, P = 0.024) and head shadow effects (Z = -3.103, P = 0.002). There was no significant difference in root mean square error degree (RMSE) and hemifield identification scores for SLT testing. Pupillometry was performed to measure listening effort and the results revealed that the degree of pupillary dilatation decreased under the condition of quiet, 0 dB signal to noise ratio (SNR) and 3 dB SNR. The total score for HHIE decreased significantly (Z = -3.130, P = 0.002) while the SSQ score increased significantly (Z = -2.216, P = 0.027). CONCLUSIONS: The Ponto bone-anchored hearing system showed significant clinical benefit in Korean patients with conductive and mixed hearing loss and SSD.

Hearing and Speech Perception for People With Hearing Loss Using Personal Sound Amplification Products.

BACKGROUND: Hearing loss (HL) is the most common chronic disease and has been linked to negative health outcomes. Hearing aids (HAs) are regarded as the gold standard for HL management, however, the adoption rate of HAs is relatively low for various reasons. With this background, hearing devices, such as personal sound amplification products (PSAPs) received significant attention as an alternative to conventional HAs. This study aimed to evaluate the clinical efficacy of PSAPs in patients with mild to moderately severe HL. METHODS: Nineteen patients with mild hearing loss (MHL), 23 with moderate hearing loss (MDHL), and 15 with moderately severe hearing loss (MSHL) participated in the study. Electroacoustic analysis, simulated real-ear measurements (REMs), and three clinical evaluations were implemented. RESULTS: All devices satisfied the electroacoustic tolerances. All devices provided sufficient gain for MHL and MDHL audiograms. However, in MSHL audiogram, the gains of PSAPs were insufficient, especially for high frequencies. In terms of clinical evaluations, sound-field audiometry showed significant improvements between aided and unaided thresholds in all groups for all devices (P < 0.001). Significant improvements of word recognition scores were only shown for HAs between aided and unaided conditions. The Korean version of the Hearing In Noise Test did not show any consistent findings for all devices and groups. CONCLUSION: Certain PSAPs are beneficial for improving hearing and speech perception in patients with HL. Well-chosen PSAPs could be an alternative hearing rehabilitation option for these patients.

Factors Influencing Hearing Aid Adoption in Patients With Hearing Loss in Korea.

BACKGROUND: The purpose of this study was two-fold: 1) to identify differences in the characteristics of adopters and non-adopters of hearing aids (HAs); and 2) to investigate factors influencing the purchase of HA. METHODS: This study was conducted among 1,464 subjects (818 male and 646 female) with hearing loss. A national face-to-face survey was performed from August 2019 to October 2020 by otologists or HA experts. The questionnaire consisted of three domains: demographic, audiological, and HA-related domains. Multivariate logistic regression analysis was performed after adjusting for degree of hearing loss. RESULTS: The mean age of the participants was 70.4 ± 12.2 years. Of the 1,464 respondents, 1,190 (81.3%) had already purchased HA. We identified educational level, household income, hearing loss period, place of HA purchase, and government HA assistance program status as factors influencing HA adoption. Among these factors, third party reimbursement was the most important factor affecting HA purchase intent. The main reasons for not adopting HA were feeling that their hearing was adequate, inability to afford HA, and perceptions that HA are uncomfortable. CONCLUSION: Various factors are involved in the purchase of HA, but disabled registration status and third party reimbursement were identified as the most critical factors. In the future, the government should take a more active role in increasing the distribution of HA to patients with hearing loss.

Duty-Cycle-Based Pre-Emption Protocol for Emergency Networks.

This paper proposes a new duty-cycle-based protocol for transmitting emergent data with high priority and low latency in a sensor network environment. To reduce power consumption, the duty cycle protocol is divided into a listen section and a sleep section, and data can only be received when the receiving node is in the listen section. In this paper, high-priority transmission preempts low-priority transmission by distinguishing between high-priority preamble and low-priority preamble. However, even when a high priority transmission preempts a low priority transmission such that the high priority transmission is received first, if the sleep period is very long, the delay may be large. To solve this problem, the high priority short preamble and high priority data reduce receiver sensitivity and increase coverage through repeated transmission. If there are several receiving nodes within a wide coverage, the receiving node that wakes up first can receive the transmission, thus reducing the delay. The delay can also be further reduced by alternately reducing the sleep cycle of one node among the receiving nodes that can receive it. This paper shows that emergent data can be transmitted effectively and reliably by reducing the delay of high-priority data to a minimum through the use of preemption, coverage extension, and an asymmetric sleep cycle.

Alleviation of LPS-Induced Inflammation and Septic Shock by Lactiplantibacillus plantarum K8 Lysates.

We previously showed that Lactiplantibacillus plantarum K8 and its cell wall components have immunoregulatory effects. In this study, we demonstrate that pre-treatment of L. plantarum K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The down-regulation of signals may be caused by the induction of negative regulators involved in toll-like receptor (TLR)-mediated signaling. However, co-treatment with high concentrations of L. plantarum K8 lysates and lipopolysaccharide (LPS) activated the late signaling of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB pathways and resulted in the induction of absent in melanoma 2 (AIM2) inflammasome-mediated interleukin (IL)-1ß secretion. Intraperitoneal injection of L. plantarum K8 lysates in LPS-induced endotoxin shock mice alleviated mortality and reduced serum tumor-necrosis factor (TNF)-α, IL-1ß, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In addition, the mRNA levels of TNF-α, IL-1ß, and IL-6 decreased in livers from mice injected with L. plantarum K8 followed by LPS. Hematoxylin and eosin (H&E) staining of the liver showed that the cell size was enlarged by LPS injection and slightly reduced by L. plantarum K8 lysate pre-injection followed by LPS injection. Macrophage infiltration of the liver also decreased in response to the combination injection compared with mice injected with only LPS. Taken together, our results show that although L. plantarum K8 lysates differentially regulated the production of LPS-induced inflammatory cytokines in THP-1 cells, the lysates inhibited overall inflammation in mice. Thus, this study suggests that L. plantarum K8 lysates could be developed as a substance that modulates immune homeostasis by regulating inflammation.

Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer.

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.

Longitudinal analysis of serum neurofilament light chain: A potential therapeutic monitoring biomarker for multiple sclerosis.

OBJECTIVES: Serum neurofilament light chain (sNfL) has been proposed a potential biomarker in multiple sclerosis (MS) based on mainly cross-sectional observations in Western population. To clarify clinical implication of sNfL, we longitudinally analysed sNfL levels at multiple time points in Korean MS patients undergoing alemtuzumab therapy. METHODS: Between 2016 and 2018, 144 sera from 17 MS patients treated with alemtuzumab at National Cancer Centre and 35 sera from 35 age- and gender-matched healthy controls (HCs) were collected for a longitudinal study with a mean 21-month follow-up. The sera were measured for sNfL levels using single molecule array. Patients were classified into two groups: evidence of disease activity (EDA) or no evidence of disease activity (NEDA). RESULTS: During alemtuzumab therapy, sNfL levels in EDA patients were significantly higher than those in NEDA patients and HCs (p < 0.001). In longitudinal analysis, the sNfL levels were consistently low in NEDA patients, while it consistently increased in radiologically and/or clinically active status in EDA patients. All sNfL levels in radiologically and/or clinically active status samples were higher than those in inactive status samples. CONCLUSION: These results suggest that sNfL is a promising monitoring biomarker for personalized therapeutics in MS patients.

Severe B cell-mediated disease activation despite two cycles of alemtuzumab in a patient with multiple sclerosis.

Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell-mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell-mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab.

Restoration of regulatory B cell deficiency following alemtuzumab therapy in patients with relapsing multiple sclerosis.

BACKGROUND: Regulatory B cells (Bregs), which protect from autoimmunity, are deficient in multiple sclerosis (MS). Novel regulatory B cell subsets CD19+CD24hiCD38hi cells and CD19+PD-L1hi cells, with disparate regulatory mechanisms have been defined. Alemtuzumab provides a long-lasting suppression of disease activity in MS. In contrast to its documented efficacy, alemtuzumab's mechanism of action is not fully understood and information about the composition of repopulating B cell pool is scarce. AIM: To characterize repopulated B cell subsets and elucidate alemtuzumab's mechanism of action in B cell perspective. METHODS: The frequency and the absolute number of Bregs were studied in peripheral blood mononuclear cells (PBMC) of 37 MS patients and 11 healthy controls (HC). Longitudinal analysis of the frequency and the absolute number of Bregs in PBMC of 11 MS patients was evaluated, before and at 6, 9, and 12 months post alemtuzumab. RESULTS: We found deficiency of CD19+CD24hiCD38hi cells during relapse compared to remission and HC (relapse vs remission: p = 0.0006, relapse vs HC: p = 0.0004). CD19+PD-L1hi cells were deficient during relapse than remission and HC (relapse vs remission: p = 0.0113, relapse vs HC: p = 0.0007). Following alemtuzumab, the distribution of B cells shifts towards naïve phenotype and Breg deficiency is restored. The frequency of CD19+CD24hiCD38hi cells was significantly increased at 6 M and 9 M compared to 0 M (6 M vs 0 M: p = 0.0004, 9 M vs 0 M: p = 0.0079). At 9 M, the frequency of CD19+CD24hiCD38hi cells started to decrease and by 12 M the frequency was reduced compared to 6 M, although it was significantly higher than baseline level (12 M vs 0 M: p = 0.0257). The absolute number was significantly increased at 6 M and 9 M post-alemtuzumab (6 M vs 0 M: p = 0.0063, 9 M vs 0 M: p = 0.02). The frequency of CD19+PD-L1hi cells significantly increased until 12 M (6 M vs 0 M: p = 0.0004, 12 M vs 0 M: p = 0.0036). The frequency of CD19+PD-L1hi cells at 12 M was significantly higher than 9 M (p = 0.0311). We further pinpoint that CD19+CD24hiCD38hi cells were deficient at severe relapses following alemtuzumab infusion and restored during recovery. CONCLUSIONS: Our results highlight the preferential reconstitution of Bregs as a possible mechanism of action of alemtuzumab and CD19+CD24hiCD38hi cells as a potential biomarker for disease activity.

The effect of resistant starch (RS) on the bovine rumen microflora and isolation of RS-degrading bacteria.

Resistant starch (RS) in the diet reaches the large intestine without degradation, where it is decomposed by the commensal microbiota. The fermentation of RS produces secondary metabolites including short-chain fatty acids (SCFAs), which have been linked to a variety of physiological and health effects. Therefore, the availability of RS as a prebiotic is a current issue. The objectives of this study were (1) to use metagenomics to observe microbial flora changes in Bos taurus coreanae rumen fluid in the presence of RS and (2) to isolate RS-degrading microorganisms. The major microbial genus in a general rumen fluid was Succiniclasticum sp., whereas Streptococcus sp. immediately predominated after the addition of RS into the culture medium and was then drastically replaced by Lactobacillus sp. The presence of Bifidobacterium sp. was also observed continuously. Several microorganisms with high RS granule-degrading activity were identified and isolated, including B. choerinum FMB-1 and B. pseudolongum FMB-2. B. choerinum FMB-1 showed the highest RS-hydrolyzing activity and degraded almost 60% of all substrates tested. Coculture experiments demonstrated that Lactobacillus brevis ATCC 14869, which was isolated from human feces, could grow using reducing sugars generated from RS by B. choerinum FMB-1. These results suggest that Bifidobacterium spp., especially B. choerinum FMB-1, are the putative primary degrader of RS in rumen microbial flora and could be further studied as probiotic candidates.

Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases.

BACKGROUND: We evaluated the seroprevalence of myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG) and associated clinical features of patients from a large adult-dominant unselected cohort with mainly relapsing central nervous system (CNS) inflammatory diseases. We also investigate the clinical relevance of MOG-IgG through a longitudinal analysis of serological status over a 2-year follow-up period. METHODS: Serum samples from 505 patients with CNS inflammatory diseases at the National Cancer Center were analysed using cell-based assays for MOG-IgG and aquaporin-4 immunoglobulin G (AQP4-IgG). MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up. RESULTS: Twenty-two of 505 (4.4%) patients with CNS inflammatory diseases were positive for MOG-IgG. Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgG-negative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). No relapses were seen in patients when they became MOG-IgG seronegative, whereas a persistent positive serological status was observed in patients with clinical relapses despite immunotherapy. CONCLUSIONS: In a large adult-predominant unselected cohort of mainly relapsing CNS inflammatory diseases, we confirmed that NMOSD phenotype was most commonly observed in patients with MOG-IgG. A longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses.

Highly Microporous Nitrogen-doped Carbon Synthesized from Azine-linked Covalent Organic Framework and its Supercapacitor Function.

Porous carbons with nitrogen-doped (N-doped) structures are promising materials for advanced energy conversion and storage applications, including supercapacitors and fuel cell catalysts. In this study, microporous N-doped carbon was successfully fabricated through carbonization of covalent organic frameworks (COFs) with an azine-linked two-dimensional molecular network (ACOF1). In the carbonized ACOF1, micropores with diameters smaller than 1 nm are selectively formed, and a high specific surface area (1596 cm2 g-1 ) is achieved. In addition, the highly porous structure with N-doped sites results in enhancement of the electrochemical capacitance. Detailed investigation for the micropore-forming process reveals that the formation of nitrogen gas during the thermal degradation of the azine bond contributes to the microporous structure formation. Therefore, the present direct carbonization approach using COFs allows the fabrication of microporous heteroatom-doped carbons, based on molecularly designed COFs, toward future electrochemical and energy applications.

Arhgef16, a novel Elmo1 binding partner, promotes clearance of apoptotic cells via RhoG-dependent Rac1 activation.

Elmo is an evolutionarily conserved mammalian ortholog of Caenorhabditis elegans CED-12 with proposed roles during the removal of apoptotic cells, cell migration, neurite outgrowth, and myoblast fusion (Katoh and Negishi (2003) [1], Park and Tosello (2007) [2], Grimsley et al. (2004) [3], Hamoud et al. (2014) [4]). Elmo mediates these cellular processes by interacting with various proteins located in the plasma membrane, cytoplasm and nucleus, and by modulating their activities although it has no intrinsic catalytic activity (Park and Tosello (2007) [2], Hamoud et al. (2014) [4], Li et al. (2013) [5], Margaron, Fradet and Cote (2013) [6], and Mauldin et al. (2013)[7]). Because there are a limited number of proteins known to interact with Elmo, we performed a yeast two-hybrid screen using Elmo1 as bait to identify Elmo1-interacting proteins and to evaluate their mode of regulation. Arhgef16 was one of the proteins identified through the screen and subsequent analyses revealed that Arhgef16 interacted with Elmo1 in mammalian cells as well. Expression of Arhgef16 in phagocytes promoted engulfment of apoptotic cells, and engulfment mediated by Arhgef16 increased synergistically in the presence of Elmo1 but was abrogated in the absence of Elmo1. In addition, Arhgef16-mediated removal of apoptotic cells was dependent on RhoG, but independent of Dock1. Taken together, this study suggests that the newly identified Elmo1-interacting protein, Arhgef16, functions synergistically with Elmo1 to promote clearance of apoptotic cells in a RhoG-dependent and Dock1-independent manner.

The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects.

AIMS: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol. METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment. RESULTS: The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBE vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments. CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.

Carbon-nanotube-grafted glass-fiber-reinforced composites: Synthesis and mechanical properties.

Glass fibers (GFs) are commonly used as reinforcements for advanced polymer composites. To improve the interfacial shear properties and mechanical properties of GF-reinforced composites (GFRPs), carbon nanotubes (CNTs) are directly grafted onto GFs using chemical vapor deposition (CVD). However, this process requires high temperatures, which causes thermal degradation of GFs, deteriorating their mechanical properties. In this study, a low-temperature CNT-grafting process was investigated using a bimetallic catalyst introduced onto a GF fiber surface via precursor solutions. The mechanical properties of the CNT-grafted GFs fabricated at different CVD temperatures were evaluated; they consistently showed low tensile strengths at temperatures above 400 °C. Subsequently, various CNT-grafted GFRPs were manufactured, and their mechanical properties were characterized. Interestingly, the flexural strengths of the composites increased with maintained tensile strength, despite a deterioration of the CNT-grafted GF reinforcements due to the CVD process. This could be attributed to the improved interfacial shear strength (IFSS) of the CNT-grafted GFs at the fiber level, and the enhanced compressive strength and interlaminar shear strength (ILSS) of CNT-grafted GFRPs at the composite level. Considering the properties of GF through CVD processes, particularly in relation to temperature, and factors such as IFSS, ILSS, tensile, compressive and flexural properties of composite materials, grafting CNTs on GF via a CVD system demonstrated its highest optimality at 450 °C.