Sue Shin

A study on the effect of heat treatment on functional groups of pitch based activated carbon fiber using FTIR

Abstract Pitch based active carbon fibers (ACFs) were analyzed by a FTIR micro-ATR technique by introducing a very thin KBr layer on their surfaces. The ACFs were thermally treated at 600, 1100, and 1200 °C respectively, to investigate the change of their surface functionalities. As the heat treatment temperature increased, the amount of oxygen containing surface functional groups were reduced and the ACFs became more hydrophobic. When the ACFs were thermally treated, the decrease of carboxylic acid groups occurred first and ketone or quinone groups subsequently disappeared at higher heat treatment temperatures. The degree of graphitization of the ACF was increased significantly when it was treated at 1100 and 1200 °C and this was partially attributed to the release of the CO groups in the conjugated ketone or quinone structures.

A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea

Sir, Studies on the molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) have demonstrated their genetic and geographic diversity in comparisons between the community-associated (CA) and hospitalassociated (HA) strains. In addition, it has been suggested that the CA-MRSA found in Korea is genetically different from those found in other regions of the world. – 3 Recently, Kim et al. reported a nationwide survey of CA-MRSA in Korea. We also published an article on the same subject in Korea. Both studies confirmed the unique features of the Korean MRSA strains. Kim et al. designed a prospective sentinel hospital laboratory-based survey from seven hospitals in Korea. After dividing the strains into CA-MRSA and HA-MRSA, 72 isolates from each group were compared. Pathogens, colonizers and an ‘undetermined’ group were all included in the study. However, we have collected isolates from blood, wounds and pus from six hospitals in an effort to exclude possible colonization and contaminants. The enrolled hospitals did not overlap in the two articles. The definitions of CA-MRSA and multidrug resistance (MDR), and the number of antibiotics used in susceptibility testing, were slightly different in comparisons between the two articles. Kim et al. calculated the resistance rate as the number of intermediate and resistance strains over the total number of strains. In contrast, we did not consider ‘intermediate’ as resistance. Finally, we clustered MRSA isolates into representative groups based on genetic backgrounds, and clonal types were redefined according to staphylococcal chromosome cassette mec (SCCmec) type and susceptibilities. Despite these differences, both articles demonstrated similar features of the MRSA in Korea: SCCmec type IVA/ST72/Panton–Valentine leucocidin (PVL)-negative and SCCmec type II or III/ST5 or ST239/ PVL-negative strains were predominant in CA-MRSA and HA-MRSA, respectively. Kim et al. reported that for CA-MRSA, the prevalence of SCCmec type IVA was 43% and the prevalence of ST72 was 35%, and that for HA-MRSA, the prevalence of SCCmec type II or III was 82% and the prevalence of ST5 or ST239 was 86%. Similarly, our data showed that for CA-MRSA, the prevalence of SCCmec type IVA was 53.1% and the prevalence of ST72 was 27.2%, and that for HA-MRSA, the prevalence of SCCmec type II or III was 73.6% and the prevalence of ST5 or ST239 was 73.7%. PVL toxin was rarely identified in either study. In Korea, SCCmec type II or III /ST5 or ST239 was prevalent in HA-MRSA. The articles by Kim et al. and Park et al. elucidated the characteristics of CAand HA-MRSA in Korea. It is interesting that both studies were nationwide studies performed at the same time and had very similar results. We think the data shown in these articles represent the current features of both CAand HA-MRSA in Korea. However, we would like to recommend caution with regard to the conclusion that MDR in CA-MRSA was high (64%), as suggested by Kim et al. Jung et al. also reported that 60.7% of the CA-MRSA isolates were MDR. However, most of their CA-MRSA (82%) were community-onset HA-MRSA cases based on the definition of Kim et al. Another study in Korea showed that ,50% of the strains, among 20 SCCmec type IVA, were MDR when standardized according to the definition of Kim et al. After conforming to the definitions of Kim et al., we re-analysed our data and found that the overall MDR rate, in CA-MRSA, was 51.9%. However, we grouped the clonal types according to their genetic backgrounds and SCCmec type, and found antibiotic susceptibility patterns more distinctly classified (Table 1; modified from Park et al.). For example, most ST72 belonging to B-I were not MDR. B-I, D-I and E-I corresponded to SCCmec type IVA, and most of B-I and D-I were not MDR either. Therefore, the SCCmec type IVA/ST72/PVL-negative clones, the dominant CA-MRSA strains in Korea, were not MDR at least. The clonal types could have the advantage of demonstrating antibiotic susceptibility patterns more precisely than the groups defined by SCCmec only. We agree with Kim et al. and Jung et al. that there were multiple clones of CA-MRSA circulating in communities in Korea and some clones had MDR characteristics similar to HA-MRSA. Even in the dominant SCCmec type IVA in CA-MRSA, our data showed that there would be at least three different groups; however, only 30.2% were MDR. As commented on by Park et al., isolates classified as ‘undetermined’ (46.4%) were all recovered from patients with chronic otitis media; most of them belonged to ST5 or ST239, which was predominant in the HA-MRSA. These findings may explain why the authors concluded that the MDR rate was high in the CA-MRSA. If the subgroup analysis was performed for the pathogen, colonizer and undetermined groups, or the clonal type was used in the analysis, a different conclusion would be expected. In order to confirm the epidemiological characteristics, standardization of study design, classifications and definitions are required. Further study is required to monitor the current trends and detect changes when they occur both locally and worldwide.

Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.

Pharmacokinetic and pharmacodynamic profiles of lorazepam and valproate were analyzed according to uridine 5′‐diphosphate‐glucuronosyltransferase (UGT)2B7 genotype in 14 healthy subjects with UGT2B15*2/*2 genotype. Systemic clearance of lorazepam (2 mg intravenously) and area under the concentration–time curve (AUC) of valproate (600 mg once daily for 4 days) were analyzed as pharmacokinetic parameters, and area under the effect–time curve (AUEC) of psychomotor coordination tests (Vienna) was used for pharmacodynamic parameter. No significant differences were found in systemic clearances of lorazepam by UGT2B7 genotype. AUCs of valproate showed an increasing tendency as the number of UGT2B7*2 alleles increased, but the difference was insignificant. Psychometric results were significant among the UGT2B7 genotype group (AUEC_tracking 261.5±298.9 in *1/*1, and 3,396.8±947 in *2/*2, P=0.047) when the two drugs were coadministered. Our study suggests that the UGT2B7 genotype probably affects lorazepam–valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT2B7 and UGT2B15, although the effects on the pharmacokinetics are less significant.

Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin.

SummaryWe have investigated changes in the pharmacokinetics of prednisolone caused by co-administration or discontinuation of rifampin.Serial IV pharmacokinetic studies of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of rifampin co-treatment or after its withdrawal, revealed significant changes in the area under the curve, the total clearance, the non-renal clearance and the half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold plateau after 2 weeks and the half maximal effect was attained within 5 days. Neither the volume of distribution nor the protein binding of prednisolone were significantly altered.

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in healthy Korean subjects.

What is known and Objective:  Dexmedetomidine is a selective alpha2‐adrenoreceptor agonist used for sedation in critically ill patients. The current study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics and tolerability of intravenous dexmedetomidine in healthy Korean subjects.

Comparison of Explant-Derived and Enzymatic Digestion-Derived MSCs and the Growth Factors from Wharton’s Jelly

Whartons jelly is not only one of the most promising tissue sources for mesenchymal stem cells (MSCs) but also a source of natural growth factors. To prove that we can get both natural growth factors and MSCs from Whartons jelly, we compared cellular characteristics and the level of basic fibroblast growth factor (bFGF) from samples using the explant culture method to those derived from the traditional enzymatic culture method. The levels of bFGF were 27.0 ± 11.7 ng/g on day 3, 15.6 ± 11.1 ng/g on day 6, and decreased to 2.6 ± 1.2 ng/g on day 14. The total amount of bFGF released was 55.0 ± 25.6 ng/g on explant culture. Compared with the traditional enzymatic digestion method, the explant culture method showed a tendency to release higher levels of bFGF in supernatant media for the first week of culture, and the higher cellular yield at passage 0 (4.89 ± 3.2 × 105/g versus 1.75 ± 2.2 × 105/g, P = 0.01). In addition, the genes related to mitosis were upregulated in the explant-derived MSCs.

Modeling of brain D2 receptor occupancy-plasma concentration relationships with a novel antipsychotic, YKP1358, using serial PET scans in healthy volunteers

YKP1358 is a novel serotonin (5‐HT2A) and dopamine (D2) antagonist that, in preclinical studies, fits the general profile of an atypical antipsychotic. We conducted a D2 receptor occupancy study with YKP1358 in healthy volunteers using positron emission tomography (PET) to measure the D2 receptor occupancy of YKP1358 and to characterize its relationship to plasma drug concentrations. A single oral dose, parallel group, dose‐escalation (100, 200, and 250 mg) study was performed in 10 healthy male volunteers with the PET radiotracer [11C]raclopride. The D2 receptor occupancy of striatum was measured pre‐dose, and at 2, 5, and 10 h after YKP1358 administration. Serial blood samples were taken for measurement of plasma YKP1358 concentrations. D2 receptor occupancy by YKP1358 increased to 53–83% at 2 h, and then decreased afterwards, ranging from 40–64% at 5 h to 20–51% at 10 h. The YKP1358 dose‐plasma concentration relationship exhibited extensive variability, but there was a good relationship between plasma concentrations and D2 receptor occupancy that was well predicted by a sigmoid Emax model using nonlinear mixed effects modeling. To our knowledge, this is the first study in which the relationship between plasma concentration and the biomarker of D2 receptor occupancy was modeled using nonlinear mixed effects modeling. It is anticipated that these results will be useful in estimating for subsequent studies the initial doses of YKP1358 required to achieve a therapeutically effective range of D2 receptor occupancy.

Doxorubicin-induced platelet procoagulant activities: an important clue for chemotherapy-associated thrombosis.

Thrombotic risk associated with chemotherapy including doxorubicin (DOX) has been frequently reported; yet, the exact mechanism is not fully understood. Here, we report that DOX can induce procoagulant activity in platelets, an important contributor to thrombus formation. In human platelets, DOX increased phosphatidylserine (PS) exposure and PS-bearing microparticle (MP) generation. Consistently, DOX-treated platelets and generated MPs induced thrombin generation, a representative marker for procoagulant activity. DOX-induced PS exposure appeared to be from intracellular Ca²⁺ increase and ATP depletion, which resulted in the activation of scramblase and inhibition of flippase. Along with this, apoptosis was induced by DOX as determined by the dissipation of mitochondrial membrane potential (Δψ), cytochrome c release, Bax translocation, and caspase-3 activation. A Ca²⁺ chelator ethylene glycol tetraacetic acid, caspase inhibitor Q-VD-OPh, and antioxidants (vitamin C and trolox) can attenuate DOX-induced PS exposure and procoagulant activity significantly, suggesting that Ca²⁺, apoptosis, and reactive oxygen species (ROS) were involved in DOX-enhanced procoagulant activity. Importantly, rat in vivo thrombosis model demonstrated that DOX could manifest prothrombotic effects through the mediation of platelet procoagulant activity, which was accompanied by increased PS exposure and Δψ dissipation in platelets.

Black soybean extract can attenuate thrombosis through inhibition of collagen-induced platelet activation☆

Many clinical trials have demonstrated the beneficial effects of soybean (Glycine max) on general cardiovascular health. Among a variety of soybeans, black soybean is known to display diverse biological activities superior to those of yellow and green soybeans, such as in antioxidant, anti-inflammatory and anticancer activities. However, few studies have been directed on the effect of black soybean on cardiovascular function. In this study, we aimed to investigate the effect of black soybean extract (BB) on platelet activation, a key contributor to thrombotic diseases. In freshly isolated human platelets, BB has shown potent inhibitory activity on collagen-induced platelet aggregation, while yellow soybean extract had marginal activity only. BB also attenuated serotonin secretion and P-selectin expression, which are important factors for the platelet-tissue interaction along with thromboxane A(2) formation. These in vitro results were further confirmed in an ex vivo platelet aggregation measurement and in vivo venous thrombosis model where oral administration of BB reduced collagen-induced platelet aggregation and FeCl(3)-induced thrombus formation significantly. A potential active ingredient for antiplatelet effects of BB was isolated and identified to be adenosine through bioassay-directed fractionation and NMR and ESI-MS analyses. These results indicate that black soybean can be a novel dietary supplement for the prevention of cardiovascular risks and the improvement of blood circulation.

Optimizing Platelet-Rich Plasma Gel Formation by Varying Time and Gravitational Forces During Centrifugation

Despite the increasing clinical use of topical platelet-rich plasma (PRP) to enhance tissue healing and regeneration, there is no properly standardized method of autologous PRP gel preparation. This study examined the effect of the centrifugation time and gravitational force (g) on the platelet recovery ratio of PRP and determined the most effective centrifugation conditions for preparing PRP. Two-step centrifugations for preparing PRP were used in 39 subjects who had consented prior to the studys start. The separating centrifugation (Step 1, used to separate whole blood into its two main components: red blood cells and plasma) was tested from 500g to 1900g at 200g increments for 5 minutes (min), and from 100g to 1300g at 200g increments for 10 minutes. After separating centrifugation, upper plasma layer was transferred to another plain tube for the condensation centrifugation and remaining lower cell layer was discarded. The condensation centrifugation (Step 2, used to condense the platelets in the separated plasma) was tested at 1000g for 15 min, 1500g for 15 min, 2000g for 5 min and 3000g for 5 min, additionally at 1000g for 10 min and 1500g for 10 min. Platelet gelation was induced by adding 10% calcium gluconate to final PRP with volume ratio of 1:10. The optimal separating centrifugation conditions were followed by 900g for 5 minutes and the condensation conditions were followed by 1500g for 15 minutes, of which recovery ratios were 92.0 ± 3.1% and 84.3 ± 10.0%, respectively.