Complete mitochondrial genome of agar-producing red alga <i>Gracilariopsis chorda</i> (Gracilariales)

Yang, Eun Chan,Kim, Kyeong Mi,Kim, Su Yeon,Yoon, Hwan Su Informa UK Ltd. 2014 Mitochondrial DNA Vol.25 No.5

<P>We sequenced the complete mitochondrial genome of <I>Gracilariopsis chorda</I> (Gracilariales, Rhodophyta), which is an agar-producing economic red algal species distributed in the northwest Pacific. The mitogenome is 26,534  bp in length with 27.7% GC content that consists of 52 genes including 26 protein-coding, 2 rRNA and 24 tRNA genes. We compared <I>G. chorda</I> mitogenome with that of recently published <I>G. lemaneiformis</I>. Nucleotide sequence similarity between these two mitogenomes was 99.82%, however, there was significant difference in length caused by <I>trnR trnS</I> and <I>trnY</I> genes missing in <I>G. lemaneiformis</I>.</P>

Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers

Lim, Mi-sun,Seong, Sook Jin,Park, Jeonghyeon,Seo, Jeong Ju,Lee, Joomi,Yu, Kyung-Sang,Lee, Hae Won,Yoon, Young-Ran Informa UK, Ltd. 2012 Expert opinion on drug metabolism & toxicology Vol.8 No.4

<P><B><I>Objective</I>:</B> Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS).</P><P><B><I>Methods</I>:</B> Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS.</P><P><B><I>Results</I>:</B> For levofloxacin, the mean values for dose-normalized C<SUB>max</SUB> and AUC<SUB>last</SUB> with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C<SUB>max</SUB> and AUC<SUB>last</SUB> were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively.</P><P><B><I>Conclusion</I>:</B> In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.</P>

Evaluation of information in nanomaterial safety data sheets and development of international standard for guidance on preparation of nanomaterial safety data sheets

Lee, Ji Hyun,Kuk, Won Kwen,Kwon, Miran,Lee, Jong Han,Lee, Kwon Sub,Yu, Il Je Informa UK, Ltd. 2013 Nanotoxicology Vol.7 No.3

<P>Safety data sheets (SDSs) and labelling are the basic hazard communication tools for hazardous chemicals as regards their manufacture, storage, transport and other handling activities. Thus, in the context of the growing use of nanomaterials and nanomaterial-containing materials, this study evaluated the information provided in 97 nanomaterial-related SDSs according to the criteria set by the GHS (Globally Harmonized System of Classification and Labelling of Chemicals) and found that most of the SDSs did not include sufficient information on the safety of nanomaterials, such as their toxicity and physicochemical properties. The reasons for this lack of information in the nanomaterial SDSs can mainly be attributed to (1) a lack of toxicity and physicochemical property information on nanomaterials, (2) unawareness of the effectiveness of conventional exposure controls, such as local exhaust ventilation and encapsulation, and personal protective equipment (PPE), in protecting against nanomaterial exposure, (3) a lack of information on emergency and firefighting measures and (4) a lack of knowledge on how existing regulations apply to nanomaterials. Therefore, to create a consistent standard for the information provided on safety, health and environmental matters for manufactured nanomaterial-containing products, guidance for the preparation of nanomaterial-specific SDSs, including both nanomaterials and mixtures of nanomaterials with conventional non-nanoscale materials, was recently initiated by the ISO TC 229. Their guidance, in the form of a technical report, recommends that nanomaterial-related SDSs should be prepared based on a precautionary approach in terms of the toxicity and other risks associated with the nanomaterial contents within the mixture in question. One of the key recommendations in the technical report is to include additional physicochemical properties, including the particle size (average and range), size distribution aggregation/agglomeration state, shape and aspect ratio, crystallinity, specific surface area, dispersibility and dustiness, which help to distinguish the characteristics of nanomaterials from those of non-nanoscale materials. The technical report also recommends the preparation of SDSs for all nanomaterials and mixtures that meet the GHS criteria for physical, health or environmental hazards, and for all mixtures containing nanomaterials that meet the criteria for carcinogenic, toxic to reproduction or specific target organ toxicity in concentrations exceeding the cut-off limits for an SDS specified by the criteria for mixtures. Finally, the technical report recommends that SDSs be prepared for all nanomaterials, unless there is evidence that they are not hazardous.</P>

Investigation of the heating properties of platinum nanoparticles under a radiofrequency current

San, Boi Hoa,Moh, Sang Hyun,Kim, Kyeong Kyu Informa UK, Ltd. 2013 International journal of hyperthermia Vol.29 No.2

<P><I>Purpose</I>: For the potential application of platinum nanoparticles (PtNPs) in hyperthermia therapy, the heating efficiency of PtNPs in the presence of radiofrequency (RF) current generated by a capacitive electric transfer (CET) system was compared with that of gold nanoparticles (AuNPs).</P><P><I>Materials and methods</I>: PtNPs and AuNPs synthesised by citrate capping (5 nm) were exposed to an RF current of 0.35 ± 0.05 MHz in a CET system. The temperature of the solution containing various concentrations of platinum or gold NPs was monitored for 5 min at various power ranges.</P><P><I>Results</I>: When both NP solutions were exposed to an RF field at a fixed power, the temperature of the NP solution increased continuously over the 5 min of measurement. In contrast, the NP-free solutions did not show any temperature change. Both PtNPs and AuNPs can be heated in a concentration- and power-dependent manner. However, PtNPs showed a higher efficiency in generating heat compared with AuNPs in both water and the physiological buffer.</P><P><I>Conclusions</I>: The heat generating efficiency of 5-nm PtNPs was about 50% higher than that of AuNPs when they were exposed to electric current through RF. This result suggests that PtNPs are promising nanomaterials for RF-induced hyperthermia therapy.</P>

Radiofrequency ablation lesion detection using MR-based electrical conductivity imaging: A feasibility study of <i>ex vivo</i> liver experiments

Chauhan, Munish,Jeong, Woo Chul,Kim, Hyung Joong,Kwon, Oh In,Woo, Eung Je Informa UK Ltd. 2013 International journal of hyperthermia Vol.29 No.7

<P><I>Purpose</I>: The aim of this study was to show the potential of magnetic resonance electrical impedance tomography (MREIT) conductivity imaging in terms of its capability to detect ablated lesions and differentiate tissue conditions in liver radiofrequency (RF) ablation. <I>Materials and methods</I>: RF ablation procedures were performed in bovine livers using a LeVeen RF needle electrode. Ablation lesions were created using a power-controlled mode at 30, 50, and 70 W for 1, 3, and 5 min of exposure time, respectively. After the ablation, the liver was cut into several blocks including the ablated lesion, and positioned inside a phantom filled with agarose gel. Electrodes were attached on the side of the phantom and it was placed inside the MRI bore. For MREIT imaging, multi-spin-echo pulse sequence was used to obtain the magnetic flux density data according to the injection currents. <I>Results</I>: The conductivity of ablation lesions was significantly changed with the increase of exposure time (pKW < 0.01, Kruskal-Wallis test). With RF powers of 30 and 50 W, significant differences between the coagulation necrosis and hyperaemic rim were observed for more than 5 min and 3 min, respectively (pMW < 0.01, Mann-Whitney test). At 70 W, all cases showed significant differences except 3 min (pMW < 0.01). The positive correlation between the exposure time and tissue conductivity was observed in both two ablation areas (pSC < 0.01, Spearman correlation). <I>Conclusions</I>: This <I>ex vivo</I> feasibility study demonstrates that current MREIT conductivity imaging can detect liver RF ablation lesions without using any contrast media or additional MR scan.</P>

Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents

Nam, Nguyen-Hai,Huong, Tran Lan,Dung, Do Thi Mai,Dung, Phan Thi Phuong,Oanh, Dao Thi Kim,Park, Sang Ho,Kim, Kyungrok,Han, Byung Woo,Yun, Jieun,Kang, Jong Soon,Kim, Youngsoo,Han, Sang-Bae Informa UK Ltd. 2014 Journal of enzyme inhibition and medicinal chemist Vol.29 No.5

<P>Since the first histone deacetylase (HDAC) inhibitor (Zolinza®, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, <I>N<SUP>1</SUP></I>-hydroxy-<I>N</I><SUP>8</SUP>-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (<B>5b</B>), <I>N<SUP>1</SUP></I>-hydroxy-<I>N</I><SUP>8</SUP>-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (<B>5c</B>) and <I>N<SUP>1</SUP></I>-hydroxy-<I>N</I><SUP>8</SUP>-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (<B>5d</B>), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds <B>5b</B>-<B>d</B> were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.</P>

Recent advances in pharmacophore modeling and its application to anti-influenza drug discovery

Shin, Woo-Jin,Seong, Baik Lin Informa UK, Ltd. 2013 Expert opinion on drug discovery Vol.8 No.4

<P><B><I>Introduction:</I></B> The emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus and the recent global circulation of H1N1 swine-origin influenza virus in 2009 have highlighted the need for new anti-influenza therapies. This has been made all the more important with the emergence of antiviral-resistant strains. Recent progress in achieving three-dimensional (3D) crystal structures of influenza viral proteins and efficient tools available for pharmacophore-based virtual screening are aiding us in the discovery and design of new antiviral compounds.</P><P><B><I>Areas covered:</I></B> This review discusses pharmacophore modeling as a potential cost-effective and time-saving technology for new drug discovery as an alternative to high-throughput screening. Based on this technical platform, the authors discuss current progress and future prospects for developing novel influenza antivirals against pre-existing or emerging novel targets.</P><P><B><I>Expert opinion:</I></B> Although it might be at an infant stage of development, the availability of the 3D crystal structures of influenza viral proteins is expected to accelerate the application of structure-based drug design (SBDD) and pharmacophore modeling. Furthermore, the neuraminidase inhibitor, one of the most successful examples of a SBDD, still receives great attention because of its superb antiviral activities and the resistance of influenza strains to oseltamivir. However, despite much success, pharmacophore-based virtual screening exhibits limited predictive power in hit identification. Further improvements in pharmacophore detection algorithms, proper combinations of <I>in silico</I> methods as well as judicious choosing of compounds are expected to improve the hit rate. With the help of these technologies, the discovery of anti-influenza agents will be accelerated.</P>

Poly(lactide-co-glycolide acid)/biphasic calcium phosphate composite coating on a porous scaffold to deliver simvastatin for bone tissue engineering

Sadiasa, Alexander,Kim, Min Sung,Lee, Byong Taek Informa UK Ltd. 2013 Journal of drug targeting Vol.21 No.8

<P>In this study, simvastatin (SIM) drug incorporated poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactic-co-glycolide) (PLGA)/biphasic calcium phosphate (BCP) composite material (SPB) was coated on the BCP/ZrO<SUB>2</SUB> (SPB-BCP/ZrO<SUB>2</SUB>) scaffold to enhance the mechanical and bioactive properties of the BCP/ZrO<SUB>2</SUB> scaffold for bone engineering applications. The composite coating was prepared by combining different ratios of PLGA and BCP (1:2, 1:1, 2:1). After completion of the coating process, the compressive strength of the scaffolds was shown to increase with an increase in PLGA concentration from 8.5 ± 0.52 MPa for the SPB1-BCP/ZrO<SUB>2</SUB> (1:2) to 11 ± 0.65 MPa for SPB3-BCP/ZrO<SUB>2</SUB> (2:1) scaffolds when PLGA concentration was increased. Furthermore, the increase of PLGA in the coating composition corresponds to a decrease in porosity, degradation rate and weight loss of the scaffolds after 4 weeks. SIM release study demonstrated sustained release of the drug for the three kinds of scaffolds with improved biocompatibility. The increase of PLGA concentration also resulted in a lower release rate of SIM. Thus, the lower release rate of SIM brought upon by the increase of PLGA concentration further enhanced the performance of the scaffold <I>in vitro</I> making it a promising approach in the field of bone tissue regeneration.</P>

Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model

Lee, Jangwook,Cha, Min-Ji,Lim, Kwang Suk,Kim, Jang-Kyung,Lee, Sang-Kyung,Kim, Yong-Hee,Hwang, Ki-Chul,Lee, Kuen Yong Informa UK Ltd. 2013 Journal of drug targeting Vol.21 No.9

<P>Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactic-<I>co</I>-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks <I>in vitro</I>. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated <I>in vivo</I>. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.</P>

Comment on: The relationship between statins and depression: a review of the literature

Informa UK, Ltd. 2013 Expert opinion on pharmacotherapy Vol.14 No.17