BioScience Trends
Online ISSN : 1881-7823
Print ISSN : 1881-7815
ISSN-L : 1881-7815
Volume 6, Issue 2
Displaying 1-8 of 8 articles from this issue
Policy Forum
  • Peipei Song, Jianjun Gao, Yoshinori Inagaki, Norihiro Kokudo, Wei Tang
    2012 Volume 6 Issue 2 Pages 48-51
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    Intractable and rare diseases are an important public health issue and a challenge to medical care. In recent years, much progress has been made in the United States (US), the European Union (EU), and some parts of Asia including Japan, South Korea, and Taiwan, involving specific legislation to encourage discovery and development of orphan drugs, patients' advocacy organizations to provide vast information on intractable and rare diseases and improve patients' access to healthcare, special research programs to strengthen basic and applied research on intractable and rare diseases, and so on. While China is also actively promoting regulation of intractable and rare diseases, but still lags far behind the US, EU, Japan, and other countries and regions with orphan drug legislation. Based on systematic analysis of the current status and future perspectives for intractable and rare diseases in Asia, we recommend that three important aspects of support from government, patients' advocacy organizations and rare disease registry networks, special research programs and global information exchange platform, should be given great attention in promoting the development of intractable and rare diseases research in Asian countries.
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Brief Report
  • Kun Hu, Xuanyun Huang, Yousheng Jiang, Junqiang Qiu, Wei Fang, Xianle ...
    2012 Volume 6 Issue 2 Pages 52-56
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    To generate antibodies against small molecules, it is necessary to couple them as haptens to large carriers such as proteins. However, the immunogenicity of the conjugates usually has no linear correlation with the hapten-protein ratio, which may lead to large variations in the character of the desired antibodies. In the present study, ciprofloxacin (CPFX) was coupled to bovine serum albumin (BSA) in five different proportions using a modified carbodiimide method. The conjugates were characterized qualitatively by spectrophotometric absorption and electrophoresis methods. Mass spectrometry and the trinitrobenzene sulfonic acid method were adopted to assay the density of conjugates quantitatively. As a result, CPFX-BSA conjugates with various hapten densities (21-30 molecules per carrier protein) were obtained. After immunization in mice, ELISA tests showed that the antisera titer increased gradually with the increase of hapten density. The antibody obtained from the mice showed high sensitivity toward CPFX. These results revealed the relationship between hapten density and immunogenicity as well as an optimized conjugation approach for immunization purposes.
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Original Articles
  • Vatsal Singh, Saurabh Pandey, Abhijeet Singh, Rishabh Gupta, Rajendra ...
    2012 Volume 6 Issue 2 Pages 57-62
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    Snoring can impair lifestyle and cause late cardiopulmonary complications. Early detection of snoring and timely intervention during adolescence can avoid complications. A single center prospective cross-sectional study was conducted in 548 undergraduate 17-25 years old undergraduate medical students of CSM Medical University, Lucknow, who were interviewed on the basis of the modified Berlin Questionnaire along with their room-partners describing their snoring habits. Ninety-seven (17.7%) subjects were found to be snorers. Risk factors viz. day time sleepiness (European Stroke Scale (ESS) scores), smoking habits, alcohol intake, neck size and BMI were observed. The proportion of males, smokers, BMI, neck size and ESS scores were significantly (p < 0.001) higher in snorers than non snorers. Logistic regression found sex (OR = 5.73, 95% CI = 2.11-15.61), smoking (OR = 2.20, 95% CI = 0.97-5.62), BMI (OR = 3.16, 95% CI = 1.09-7.36) and neck size (OR = 2.03, 95% CI = 0.79-6.35) as significant (p < 0.01) independent risk factors for snoring. A clinically significant form of Sleep Disordered Breathing (Habitual snoring, ESS score ≥ 11 and BMI ≥ 25 kg/m2) was suspected in 4 (0.7%) students. The findings of this study may also be validated in the general population. The study concluded that male undergraduate medical students are at a high risk for developing snoring habits.
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  • Jing Luan, Yazhou Cui, Yongying Zhang, Xiaoyan Zhou, Genglin Zhang, Ji ...
    2012 Volume 6 Issue 2 Pages 63-69
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    The aim of the study was to investigate the effect of C-X-C chemokine receptor type 4 (CXCR4) inhibitor AMD3100 on the osteogenic differentiation of pre-osteoblastic cell line MC3T3-E1. In this study we found that blocking SDF-1/CXCR4 signaling with AMD3100 strongly suppressed osteogenic differentiation in MC3T3-E1 cells, as evidenced by an early decrease in the activity of alkaline phosphatase (ALP), and down-regulation of mRNA expression of the osteogenic master regulator Runx2, ALP, osteocalcin, and progressive ankylosis genes. Moreover, we found that the regulatory effect of AMD3100 might be mediated via intracellular STAT3 activation. However, AMD3100 exerted no significant effect on generation of matrix mineralization at the terminal stage of osteogenic induction. In conclusion, our results demonstrated an inhibitory role of AMD3100 in osteogenic differentiation of MC3T3-E1 cells, especially in the early stage, which provides novel insights into the effect of CXCR4 antagonists on modulation of osteogenesis.
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  • Mitsuaki Muroya, Kyungho Chang, Kanji Uchida, Masahiko Bougaki, Yoshit ...
    2012 Volume 6 Issue 2 Pages 70-80
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    Supplementary material
    Epithelial cell injury under hyperinflammatory conditions is critical in the development of septic acute lung injury (ALI). The aim of the present study is to analyze the cytotoxic effects of a mixture of proinflammatory cytokines in the human alveolar epithelial cell line A549. The cytotoxicity of proinflammatory cytokines were assessed in A549 cells by measuring lactate dehydrogenase released into the culture medium and by crystal violet staining of surviving cells. Activation of the caspase-dependent apoptotic pathway was evaluated by monitoring cleavage of cytokeratin 18 by caspases using enzyme-liked immunosorbent assay (ELISA). To estimate the cytotoxic signaling pathways responsible for epithelial injury, agents with antiinflammatory or antioxidative properties were extensively screened for cytoprotective effects in the inflammation-associated epithelial injury model. The present study revealed that inflammatory cytokines exerted cytotoxicity in A549 cells. A mixture of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), designated as cytomix, augmented cytotoxicity compared with each individual cytokine. Treatment with glucocorticoid (dexamethasone), tetracycline-derived antiinflammatory antibiotics (minocycline or doxycycline), angiotensin II receptor blockers (losartan or telmisartan), or antioxidants (dimethyl sulfoxide, catalase) attenuated cytomix-induced cytotoxicity, including caspase activation. These results implied that inflammatory cytokines alone could cause alveolar epithelial injury in the pathophysiology of septic ALI. Caspase-dependent apoptosis was speculated to be one mechanism responsible for the cytokine-induced cytotoxicity. Agents with antiinflammatory or antioxidative properties such as glucocorticoid, tetracycline-derived antibiotics, angiotensin II receptor blockers, or direct antioxidants showed substantial effect in attenuating cytokine-induced cytotoxicity and may be candidates for treatment options.
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  • Ting Zhao, Yang Yang, Aizhen Zong, Haining Tan, Xinlei Song, Shuo Meng ...
    2012 Volume 6 Issue 2 Pages 81-88
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. In the present study, HSA was N-terminally PEGylated and a PEGylated HSA (PEG-HSA) carrying one chain of PEG (20 kDa) per HSA molecule was obtained. The purity, secondary structure and hydrodynamic radius of the modified protein were characterized using sodium dodecyl sulfate polyacrylamide gel electrophoresis, circular dichroism measurements, and dynamic light scattering, respectively. The pharmacokinetics in normal mice and vascular permeability of the PEG-HSA in a lipopolysaccharide-induced acute lung injury mice model were evaluated. The results showed that the biological half-life of the modified HSA was approximately 2.2 times of that of native HSA, and PEG-HSA had a lower vascular permeability which suggested that PEGylation of HSA could reduce extravasation into interstitial space. It can be inferred that due to the prolonged half-life time and enhanced vascular retention, the molecularly homogeneous PEG-HSA may be a superior candidate as a plasma volume expander in treating capillary permeability increase related illness.
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  • Junming Wang, Zhang Yueyue, Yasu Zhang, Ying Cui, Ju Liu, Binfeng Zhan ...
    2012 Volume 6 Issue 2 Pages 89-97
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study was undertaken to investigate protection of L. christinae against acute alcohol-induced liver injury in mice, the related mechanism of oxidative stress and its hepatoprotective chemical compound for the first time. Mice were orally administered alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L. christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric administration (i.g.) except the normal group. Serum and liver tissue samples were collected 6 h after alcohol administration and the amount of quercetin in ET was analyzed by high-performance liquid chromatography (HPLC) with a diode array detector (DAD). The results showed that alcohol-induced elevated serum alanine transferase (ALT) and aspartate transaminase (AST) activities were significantly reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg), respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels significantly decreased, while glutathione amounts, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities all increased in livers of ET-, quercetin-, and bifendate-treated mice. Besides, amount of quercetin in ET was 1.03%. Taken together, our results indicate that L. christinae can protect against acute alcohol-induced liver injury in mice, the potential mechanism can be related to inhibiting liver oxidative stress injury, and its main hepatoprotective compound is quercetin, for the first time.
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Case Report
  • Suguru Yamashita, Junichi Arita, Takashi Sasaki, Junichi Kaneko, Taku ...
    2012 Volume 6 Issue 2 Pages 98-102
    Published: April 30, 2012
    Released on J-STAGE: June 13, 2014
    JOURNAL FREE ACCESS
    We report a case of intrahepatic cholangiocarcinoma with biliary lithiasis arising 47 years after surgery for a congenital biliary dilatation (CBD). A 62-year-old woman was admitted for the investigation of a liver tumor. She had undergone a choledochoduodenostomy at the age of 15 years for CBD and resection of an extrahepatic bile duct with choledochojejunostomy because of cholangitis at the age of 55 years. An enhanced computed tomography (CT) revealed a liver tumor 50 mm in diameter in the S6 region with surrounding lymph node swelling and intrahepatic metastatic lesions in the S8 region. A drip infusion cholangiographic CT showed biliary lithiases in the left liver. An extended right hepatectomy and lymph node dissection was considered but was abandoned because of suspicions of liver functional insufficiency as a result of biliary lithiasis. She underwent biliary lithotomy through a percutaneous transhepatic cholangioscopy and subsequent systemic chemotherapy.
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