Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
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Volume 8 , Issue 2
Showing 1-8 articles out of 8 articles from the selected issue
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Policy Forum
  • Peipei Song, Wei Tang, Kiyoshi Hasegawa, Norihiro Kokudo
    Volume 8 (2014) Issue 2 Pages 64-70
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Since the European Association for the Study of the Liver published their guidelines for hepatocellular carcinoma HCC (EASL Guideline) in 2001, there have been many explorations of "transferring best current evidence into clinical decision-making" around the worldwide. Comparative analysis on current 17 characteristic guidelines for HCC indicated that evidence-based clinical practice guidelines for HCC are urgently needed and appropriate constructing approach is the factor most significantly influencing their implementation. The construction of evidence-based clinical practice guidelines for HCC in Japan made a good example of this practice. In accordance with evidence-based medicine (EBM), the first version of the J-HCC Guidelines was published in 2005, then revised in 2009, and the third version has just been published on October 15, 2013 with the incorporation of new evidence, which marks the construction of evidence-based clinical practice guidelines for HCC step into a systematic process in Japan. In order to make a more clear description on how to construct evidence-based clinical practice guidelines for HCC in Japan, the three versions of the J-HCC Guidelines were comparatively analyzed in this paper. Focus on methodology used to develop the updated version, the decision tree of 2013 J-HCC Guideline and its features were also revealed. It is expected that J-HCC Guidelines could be useful not only for Japanese physicians and patients in decision making at every clinical step, but also to benefit users internationally with the accumulated evidence and its interpretation in the guidelines.
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Review
  • Kazuharu Ienaga, Chan Hum Park, Takako Yokozawa
    Volume 8 (2014) Issue 2 Pages 71-75
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Both the formation and reactions of hydroxyl radical (•OH) are quantitative chemical reactions even in mammalians, and so we can reproduce such in vivo reactions in test tubes. Daily urinary excretions of some reaction products have been used to estimate the amount of •OH produced daily. Although urinary 8-hydroxydeoxyguanosine (8-OHdG) is a well-known marker of •OH, we have shown that creatol (CTL: 5-hydroxycreatinine), an •OH adduct of creatinine (Crn), and its metabolite, methylguanidine (MG), are better markers, because the amount of •OH scavenged by deoxyguanosine (dG) in the body is negligible. We measured CTL and MG together with Crn in 24-h urine, and calculated their molar sum, CTL + MG, providing a daily estimate of moles of •OH scavenged with Crn, and, from the molar ratio (CTL + MG)/Crn, we can calculate the percentage of Crn that was used to scavenge •OH. Healthy subjects and normal rats were indicated to use circa (ca.) 0.2 and 0.3% of Crn in order to scavenge •OH, respectively, because the corresponding ratios, scavenged •OH/Crn, were 2.2 and 3.0 mmole/mole (24-h urine) (Crn scavenged ca. 20-25 μmole and ca. 200 pmole of •OH in healthy subjects and normal rats, respectively). Since 8-OHdG/Crn has been reported to be 1.9 μmole/mole (24-h urine), the daily scavenging capacity with Crn is 103-fold more than dG. In patients with chronic renal failure (CRF) or chronic kidney disease (CKD) at stages 3-5: glomerular filtration rate (GFR) < 60 mL/min/1.73 m2, •OH levels increased in proportion to the severity of CKD: up to ca. 3% of Crn was used daily in order to scavenge •OH. Although the accumulation of MG in organs has not been reported except for the brain and skin tissues in normal animals, •OH increases markedly and MG becomes detectable in all organs such as the kidney, liver, and heart in CRF rats.
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Brief Report
  • Rong Wang, Zhenzhen Liu, Lupei Du, Minyong Li
    Volume 8 (2014) Issue 2 Pages 76-83
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Cardiac arrhythmia is a major cause of death in the world. Among many delayed rectifier potassium currents, the rapid delayed rectifier K current (IKr) plays an important role in the repolarization of cardiac tissue. The inhibition of IKr can delay repolarization and lead to an increase in the QT interval of the electrocardiogram, which is the treatment mechanism of Class III antiarrhythmic agents. Therefore, IKr can be considered as the drug target for the treatment of cardiac arrhythmia. In the current study, a series of 4-chromanone compounds (WR1-WR12) were well designed and synthesized as IKr inhibitors. The results disclosed that two compounds displayed potent inhibitory activities against IKr. Moreover, our structure-activity relationship results might provide necessary information for the rational design of inhibitors for IKr.
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Original Articles
  • Yanli Dou, Xiaoling Wang, Daifeng Jiang, Haiying Wang, Yang Jiao, Hong ...
    Volume 8 (2014) Issue 2 Pages 84-88
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Three new anthraquinone derivatives (1-3) and one new artifact (4) were isolated, along with six known anthraquinone derivatives (5-10) and three xanthones (11-13), from a culture of an endolichenic fungus, Aspergillus versicolor, that was isolated from the lichen Lobaria retigera. The structures of these substances were determined on the basis of 1D and 2D (COSY, HMQC, and HMBC) NMR and MS analyses. The substances 1-4 were also tested for their cytotoxic activity.
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  • Samir K. Gupta, Bhavna Kantesaria, Paul Glue
    Volume 8 (2014) Issue 2 Pages 89-95
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Although ribavirin is minimally cleared by renal elimination, its pharmacokinetics are substantially altered in patients with chronic renal impairment. This open-label study assessed the pharmacokinetics of single 400-mg oral and intravenous (IV) doses of ribavirin in two healthy volunteers and 12 patients with varying degrees of chronic renal impairment. Blood and urine samples were collected pre-dose and up to 168 h post-dose for pharmacokinetic analyses. Ribavirin area under the plasma concentration-time curve from time zero to time of final quantifiable sample and maximum plasma concentration values were increased, and total plasma clearance (CL), renal clearance (CLr), non-renal clearance (CLnr), volume of distribution at steady state (Vdss), and amount excreted values were reduced in patients with renal dysfunction compared with those who had normal renal function. Following IV administration, mean CLr was 54%, 23%, and 10% in patients with mild, moderate, and severe renal dysfunction, respectively, relative to control subjects, and was 56%, 28%, and 9% of control values after oral dosing. After IV dosing, mean CLnr was 94%, 76%, and 75% of control values in patients with mild, moderate, and severe renal dysfunction, respectively, and was 54%, 48%, and 27% of control values after oral dosing. Mean oral bioavailability of ribavirin was 35%, 60%, 57%, and 71% in control subjects and patients with mild, moderate, and severe renal dysfunction, respectively. These data indicate that there are multiple mechanisms (increased oral bioavailability, reduced CLr and CLnr, reduced Vd) contributing to altered ribavirin pharmacokinetics in chronic renal impairment.
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Commentary
  • Kenji Karako, Qiong Wu, Jianjun Gao
    Volume 8 (2014) Issue 2 Pages 96-97
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Medical imaging plays an increasingly important role in the diagnosis and treatment of disease. Currently, medical equipment mainly has two-dimensional (2D) imaging systems. Although this conventional imaging largely satisfies clinical requirements, it cannot depict pathologic changes in 3 dimensions. The development of three-dimensional (3D) imaging technology has encouraged advances in medical imaging. Three-dimensional imaging technology offers doctors much more information on a pathology than 2D imaging, thus significantly improving diagnostic capability and the quality of treatment. Moreover, the combination of 3D imaging with augmented reality significantly improves surgical navigation process. The advantages of 3D imaging technology have made it an important component of technological progress in the field of medical imaging.
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  • Jiwei Huang, Yong Zeng
    Volume 8 (2014) Issue 2 Pages 98-99
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    Hepatocellular carcinoma (HCC) is a severe condition that is found worldwide. The current methods of HCC screening and diagnosis depend mainly on tumor imaging techniques. Using tumor biomarkers to detect cancer has helped to screen for disease and avoid wasting medical resources. Serum α-fetoprotein (AFP), a glycoform of AFP that reacts with Lens culinaris agglutinin (AFP-L3), and des-gamma carboxyprothrombin (DCP) are biomarkers commonly used to detect HCC in medical practice around the world. However, each of these biomarkers is imperfect when used alone and each has limitations in terms of the sensitivity and specificity with which it detects HCC. Presumably, a combination of these biomarkers is a practical way to improve their performance. That said, novel biomarkers of HCC are being sought to diagnose the disease and also to optimize the treatment modality, to predict prognosis or recurrence, and to discover novel targets for therapeutic interventions.
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Letter
  • Yang Sun, Hongzhou Lu
    Volume 8 (2014) Issue 2 Pages 100-101
    Released: May 11, 2014
    JOURNALS FREE ACCESS
    The A/H7N9 avian influenza virus sparked global concerns about public health. The media published numerous reports about emerging infectious diseases, including their clinical characteristics and genomic information. However, outbreaks of A/H7N9 posed a real challenge to China's emergency management and especially its dealing with the media. This study analyzes ways to deal with the media during A/H7N9 crises and it proposes a shift in public emergency management from an "Impact-Responsive" approach to a "PreventionActive" approach. A "Prevention-Active" approach should be used when dealing with the media during subsequent outbreaks.
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