Kyung-Sun Kim

Doxorubicin-induced platelet cytotoxicity: a new contributory factor for doxorubicin-mediated thrombocytopenia.

Summary.  Background: Doxorubicin (DOX) is a widely used anticancer drug for solid tumors and hematologic malignancy, but its active use is hampered by serious adverse effects, including thrombocytopenia. Although bone marrow toxicity of DOX has been suggested to be the sole mechanism underlying the reduced platelet counts, the direct effects of DOX on platelets have never been examined. Objective: Here, we investigated the DOX‐induced platelet cytotoxicity and its underlying mechanism in an effort to elucidate the contribution of platelet cytotoxicity to DOX‐induced thrombocytopenia. Results: In freshly isolated human platelets, DOX induced platelet cytotoxicity in a time‐dependent and concentration‐dependent manner. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent protein thiol depletion were shown to underlie the DOX‐induced platelet cytotoxicity. Conspicuously, DOX‐treated platelets displayed apoptotic features such as caspase‐3 activation, reduced mitochondrial transmembrane potential, and phosphatidylserine exposure. Decreased glutathiolation of procaspase‐3 was shown to be a link between protein thiol depletion and caspase‐3 activation. It is of note that DOX‐mediated platelet cytotoxicity was significantly enhanced by shear stress, a common complicating factor in cancer patients. These in vitro results were further confirmed by an in vivo animal model, where administration of DOX induced a platelet count decrease, ROS generation, caspase‐3 activation, protein thiol depletion, and damaged platelet integrity. Conclusion: We demonstrated that DOX can directly induce platelet cytotoxicity through ROS generation, decreased glutathione levels, and protein thiol depletion. We believe that this study provides important evidence for the role of DOX‐induced platelet cytotoxicity in the development of thrombocytopenia in DOX‐treated patients.

Plasma uniformity and phase-controlled etching in a very high frequency capacitive discharge

The influence of controlled phase shift between very high frequency (100MHz) voltages applied to the powered electrodes on the plasma uniformity and etch rate was studied in a capacitive triode-type reactor. Radial profiles of plasma optical emission were measured as a function of the phase shift in process (C4F8∕O2∕Ar) plasma with the low frequency bias power both turned off and on. Radial profiles of KrF photoresist etch rate over a 300mm wafer were obtained in the same conditions (with the bias power turned on). Besides, plasma density at the wafer center and edge was measured versus the phase shift in pure Ar plasma. It occurred that all measured characteristics strongly depend on the phase shift and correlate with each other. It has been shown that the phase-shift control can considerably improve both the plasma and etch-rate uniformity in very high-frequency capacitive reactors.

Changes in salivary periodontal pathogens after orthodontic treatment: An in vivo prospective study.

OBJECTIVE   To analyze the initial changes in salivary levels of periodontal pathogens after orthodontic treatment with fixed appliances. MATERIALS AND METHODS   The subjects consisted of 54 adult patients. The Simplified Oral Hygiene Index, Plaque Index, and Gingival Index were measured as periodontal parameters. Both the plaque and gingival indexes were obtained from the central and lateral incisors and first molars of both arches. Whole saliva and periodontal parameters were obtained at the following four time points: immediately before debonding (T1), 1 week after debonding (T2), 5 weeks after debonding (T3), and 13 weeks after debonding (T4). Repeated measures analysis of variance was used to determine salivary bacterial levels and periodontal parameters among the four time points after quantifying salivary levels of Aggregatibacter actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythia (Tf), and total bacteria using the real-time polymerase chain reaction. RESULTS   All periodontal parameters were significantly decreased immediately after debonding (T2). The salivary levels of total bacteria and Pg were decreased at T3, while Pi and Tf levels were decreased at T4. However, the amount of Aa and Fn remained at similar levels in saliva during the experimental period. Interestingly, Aa and Fn were present in saliva at higher levels than were Pg, Pi, and Tf. CONCLUSION   The higher salivary levels of Aa and Fn after debonding suggests that the risk of periodontal problems cannot be completely eliminated by the removal of fixed orthodontic appliances during the initial retention period, despite improved oral hygiene.

An effect of nitrogen on magnetic properties and microstructure of Fe–Nb–B–N nanocrystalline thin films

Fe–Nb–B–N films with good soft magnetic properties were fabricated by Ar+N2 reactive sputtering. The quaternary films have better soft magnetic properties than that of Fe–Nb–B films. The best magnetic properties are saturation magnetization of 16.5 kG, coercivity of 0.13 Oe and effective permeability of about 5000 up to 10 MHz. It was observed by transmission electron microscopy that the Fe–Nb–B–N thin film annealed at 590 °C consisted of three phases: a fine α-Fe phase whose grain size is around 7 nm, a Nb–B rich amorphous phase and NbN precipitates with the size of less than 3 nm. The fine grained α-Fe structure, together with finely dispersed NbN precipitates and the amorphous boundary phase are considered to be a main factor for the good magnetic properties.

Compositional differences in multi-species biofilms formed on various orthodontic adhesives

Objectives To investigate the aspects of multi-species biofilm formation on various orthodontic adhesives with different surface characteristics. Methods Multi-species biofilms using 13 bacterial species were grown on the surfaces of composite, compomer, and resin-modified glass-ionomer cement (RMGI). The changes in Streptococcus mutans (Sm), Streptococcus sobrinus (Ss), Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and total bacteria were determined at day 1 (T1) and day 4 (T2) using real-time polymerase chain reaction. Surface roughness (SR), surface free energy (SFE), and surface texture were analyzed to explain the differences in bacterial compositions among the adhesives. Repeated measures analysis of variance was used to determine time-related changes in bacterial compositions with respect to adhesive type. The Kruskal-Wallis test was used to determine differences in SR and SFE among the adhesives. Results There were no significant differences in the adhesion of total bacteria among the adhesives; however, the adhesion of Sm, Ss, and Pg was higher to RMGI than the other adhesives. The amount of Sm, Ss, and total bacteria increased from T1 to T2, while Pg and Aa decreased from T1 to T2. RMGI showed a rougher surface relative to composite or compomer due to the presence of micro-pores and/or flaws. Compomer had the greatest SFE followed by RMGI and composite. Interestingly, SR differences were about 10 times greater than SFE differences among the adhesives. Conclusions Considering the greater differences in SR than SFE among the adhesives, the rougher surface of RMGI may cause greater adhesion of Sm, Ss, and Pg.

Antimicrobial and physical characteristics of orthodontic primers containing antimicrobial agents.

OBJECTIVE To compare the antimicrobial and physical properties of experimental primers containing chlorhexidine (CHX) or ursolic acid (UA) with a commercial primer. MATERIALS AND METHODS Two antibacterial agents, 3 mg each of CHX and UA were incorporated respectively into 1 ml of Transbond XT primer (TX) to form antibacterial primers, TX-CHX and TX-UA. The antimicrobial activity of the three primers (TX, TX-CHX, and TX-UA) against Streptococcus mutans in both planktonic and biofilm phases was analyzed by determining minimum inhibitory and bactericidal concentrations and by performing growth and biofilm assays. Growth and biofilm assays were performed in both the absence and presence of thermocycling in a water tank to analyze the effects of water aging on the antimicrobial activities of primers. After bonding brackets onto bovine incisors using the primers, shear bond strength and mode of fracture were analyzed to compare physical properties. RESULTS TX-CHX had stronger antimicrobial activity against S. mutans in the planktonic and biofilm phases than did TX or TX-UA. When applied, TX-CHX completely inhibited the growth and biofilm formation of S. mutans . In addition, the antimicrobial activity of TX-CHX was maintained after thermocycling. However, TX-UA did not show significant antimicrobial activity compared with TX. There was no significant difference in either shear bond strength or bond failure interface among the primers. CONCLUSION Incorporation of CHX into an orthodontic primer may help prevent enamel demineralization around surfaces without compromising its physical properties.

Adhesion of periodontal pathogens to self-ligating orthodontic brackets: An in-vivo prospective study

INTRODUCTION Our aims were to analyze adhesion of periodontopathogens to self-ligating brackets (Clarity-SL [CSL], Clippy-C [CC] and Damon Q [DQ]) and to identify the relationships between bacterial adhesion and oral hygiene indexes. METHODS Central incisor brackets from the maxilla and mandible were collected from 60 patients at debonding after the plaque and gingival indexes were measured. Adhesions of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), and Tannerella forsythia (Tf) were quantitatively determined using real-time polymerase chain reactions. Factorial analysis of variance was used to analyze bacterial adhesion in relation to bracket type and jaw position. Correlation coefficients were calculated to determine the relationships between bacterial adhesion and the oral hygiene indexes. RESULTS Total bacteria showed greater adhesion to CSL than to DQ brackets, whereas Aa, Pg, and Pi adhered more to DQ than to CSL brackets. CC brackets showed an intermediate adhesion pattern between CSL and DQ brackets, but it did not differ significantly from either bracket type. Adhesion of Fn and Tf did not differ significantly among the 3 brackets. Most bacteria were detected in greater quantities in the mandibular than in the maxillary brackets. The plaque and gingival indexes were not strongly correlated with bacterial adhesion to the brackets. CONCLUSIONS Because Aa, Pg, and Pi adhered more to the DQ brackets in the mandibular area, orthodontic patients with periodontal problems should be carefully monitored in the mandibular incisors where the distance between the bracket and the gingiva is small, especially when DQ brackets are used.

Effect of Bisphenol A Glycol Methacrylate on Virulent Properties of Streptococcus mutans UA159

Bisphenol A glycidyl methacrylate (bis-GMA), which is released into the oral environment by dental composites through incomplete polymerization, hydrolysis, and mechanical degradation, can significantly influence oral ecology around resin-based materials. The purpose of this study was to investigate how bis-GMA changes the virulence properties of Streptococcus mutans, a major cariogenic bacterium in humans. The results show that bis-GMA not only inhibited the planktonic growth of cells in medium containing glucose, fructose, or mannose, but also reduced the viability of S. mutans. However, the presence of bis-GMA increased sugar transport and intracellular polysaccharide accumulation in S. mutans, thereby increasing the potential of cell persistence. In addition, bis-GMA could enhance S. mutans’s adhesion to hard surfaces and glucan synthesis, which could contribute to biofilm formation. Although free bis-GMA made cells vulnerable to acidic stress, it also provided increased resistance to hydrogen peroxide, which might confer an advantage in competition with other oral microorganisms during the early stage of biofilm development. Interestingly, the presence of bis-GMA did not change the ability of S. mutans to interact with saliva. The results suggest that leachable bis-GMA could contribute to biofilm-related secondary dental caries at the marginal interface between resin-based materials and teeth by altering the virulent properties of S. mutans, although bis-GMA reduced the planktonic growth and viability of S. mutans.