Showing papers by "Chung-Ang University published in 2007"

Colorimetric Detection of Mercuric Ion (Hg2+) in Aqueous Media using DNA-Functionalized Gold Nanoparticles

Abstract: Mercury is a widespread pollutant with distinct toxicological profiles, and it exists in a variety of different forms (metallic, ionic, and as part of organic and inorganic salts and complexes). Solvated mercuric ion (Hg), one of the most stable inorganic forms of mercury, is a caustic and carcinogenic material with high cellular toxicity. The most common organic source of mercury, methyl mercury, can accumulate in the human body through the food chain and cause serious and permanent damage to the brain with both acute and chronic toxicity. Methyl mercury is generated by microbial biomethylation in aquatic sediments from water-soluble mercuric ion (Hg). Therefore, routine detection of Hg is central to the environmental monitoring of rivers and larger bodies of water and for evaluating the safety of aquatically derived food supplies. Several methods for the detection of Hg, based upon organic fluorophores or chromophores, semiconductor nanocrystals, cyclic voltammetry, polymeric materials, proteins, and microcantilevers, have been developed. Colorimetric methods, in particular, are extremely attractive because they can be easily read out with the naked eye, in some cases at the point of use. Although there are now several chromophoric colorimetric sensors for Hg, all of them are either limited with respect to sensitivity (current limit of detection 1 mm) and selectivity, kinetically unstable, or incompatible with aqueous environments. Recently, DNA-functionalized gold nanoparticles (DNA– Au NPs) have been used in a variety of forms for the detection of proteins, oligonucleotides, certain metal ions, and other small molecules. DNA–Au NPs have high extinction coefficients (3–5 orders of magnitude higher than those of organic dye molecules) and unique distancedependent optical properties that can be chemically programmed through the use of specific DNA interconnects, which allows one, in certain cases, to detect targets of interest through colorimetric means. Moreover, these structures, when hybridized to complementary particles, exhibit extremely sharp melting transitions, which have been used to enhance the selectivity of detection systems based upon them. By using such an approach, one can typically detect nucleic acid targets in the low nanomolar to high picomolar target concentration range in colorimetric format. The ability to use such particles to detect Hg in the nanomolar concentration range in colorimetric format would be a significant advance, especially when one considers that commercial systems for detecting Hg rely on cumbersome inductively coupled plasma approaches that are not suitable for point-of-use applications. Herein, we present a highly selective and sensitive colorimetric detection method for Hg that relies on thymidine–Hg–thymidine coordination chemistry and complementary DNA–Au NPs with deliberately designed T–T mismatches. When two complementary DNA–Au NPs are combined, they form DNA-linked aggregates that can dissociate reversibly with a concomitant purple-to-red color change. 28] For our novel colorimetric Hg assay, however, we prepared two types of Au NPs (designated as probe A and probe B, see the Supporting Information), each functionalized with different thiolated-DNA sequences (probe A: 5’HS-C10-A10-T-A103’, probe B: 5’HS-C10-T10-T-T103’), which are complementary except for a single thymidine–thymidine mismatch (shown in bold; Scheme 1). Importantly, these particles also form stable aggregates and exhibit the characteristic sharp melting transitions (full width at half maximum< 1 8C) associated with aggregates formed from perfectly complementary particles, but with a lower melting temperature Tm. [17, 18] Since it is known that Hg will coordinate selectively to the bases that make up a T–T mismatch, we hypothesized that Hg would

Translation of scales in cross-cultural research: issues and techniques.

Abstract: Aims. This paper is a report of a study designed to: (i) describe issues and techniques of translation of standard measures for use in international research; (ii) identify a user-friendly and valid translation method when researchers have limited resources during translation procedure; and (iii) discuss translation issues using data from a pilot study as an example. Background. The process of translation is an important part of cross-cultural studies. Cross-cultural researchers are often confronted by the need to translate scales from one language to another and to do this with limited resources. Method. The lessons learned from our experience in a pilot study are presented to underline the importance of using appropriate translation procedures. The issues of the back-translation method are discussed to identify strategies to ensure success when translating measures. Findings. A combined technique is an appropriate method to maintain the content equivalences between the original and translated instruments in international research. There are several possible combinations of translation techniques. However, there is no gold standard of translation techniques because the research environment (e.g. accessibility and availability of bilingual people) and the research questions are different. Conclusions. It is important to use appropriate translation procedures and to employ a combined translation technique based on the research environment and questions.

Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats

Abstract: The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. Thus, the exposed population continues to increase as the applications expand. Although previous studies on silver dust, fumes, and silver compounds have revealed some insights, little is yet known about the toxicity of nano-sized silver particles, where the size and surface area are recognized as important determinants for toxicity. Thus, the inhalation toxicity of silver nanoparticles is of particular concern to ensure the health of workers and consumers. However, the dispersion of inhalable ambient nano-sized particles has been an obstacle in evaluating the effect of the inhalation of nano-sized particles on the respiratory system. Accordingly, the present study used a device that generates silver nanoparticles by evaporation/condensation using a small ceramic heater. As such, the generator was able to distribute the desired concentrations of silver nanoparticles to chambers containing experimental animals. The concentrations and distribution of the nanoparticles with respect to size were also measured directly using a differential mobility analyzer and ultrafine condensation particle counter. Therefore, the inhalation toxicity of silver nanoparticles was tested over a period of 28 days. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into 4 groups (10 rats in each group): a fresh-air control, a low-dose group (1.73 x 10(4)/cm3), a middle-dose group (1.27 x 10(5)/cm3), and a high-dose group (1.32 x 10(6) particles/cm3, 61 microg/m3). The animals were exposed to the silver nanoparticles for 6 h/day, 5 days/wk, for a total of 4 wk. The male and female rats did not show any significant changes in body weight relative to the concentration of silver nanoparticles during the 28-day experiment. Plus, there were no significant changes in the hematology and blood biochemical values in either the male or female rats. Therefore, the initial results indicated that exposure to silver nanoparticles at a concentration near the current American Conference of Governmental Industrial Hygienists (ACGIH) silver dust limit (100 microg/m3) did not appear to have any significant health effects.

A gold-nanoparticle-based real-time colorimetric screening method for endonuclease activity and inhibition.

Abstract: Nucleic acids act as the carriers of genetic information, and most organisms contain a type of enzymes called endonucleases, which can hydrolyze the phosphodiester linkages in the nucleic acid backbone. These nucleases are important for many processes involving the replication, repair, and recombination of nucleic acids. Endonucleases such as DNA gyrase and virus integrase play key roles in biological process such as the topological altering of DNA and the insertion of proviral DNA into host chromosomal DNA. Molecules that inhibit endonucleases are therefore considered candidates for a variety of antimicrobial and antiviral drugs. As such, methods for the high-throughput screening of different nuclease inhibitors have become a central part of the drug-development process. The most widely used assays include those based on the use of chromogenic or fluorogenic substrates to produce a spectrophotometric signal. In many cases, however, it is desirable to measure the reaction between an enzyme and a well-defined nucleic acid substrate of interest, as opposed to a fluorogenic or chromogenic derivative of that substrate. Historically, endonuclease activity has been screened by viscometry, radioactive labeling, and gel electrophoresis, in addition to the more recent fluorescence-based approaches. Most of these protocols are time consuming and do not provide a measure of endonuclease activity in real time. Of these methods, only fluorescence is appreciably used for highthroughput screening, and the fluorescence-based approach has just recently been implemented. Herein, we report an operationally simple colorimetric endonuclease-inhibition assay, which enables the real-time monitoring of endonuclease activity and the simultaneous determination of the efficiencies of endonuclease inhibitors (e.g., DNA-binding molecules). The new method relies on polymeric aggregates of DNA-functionalized gold nanoparticles (DNA-AuNPs) with DNA-duplex interconnects. DNA-AuNPs have been used previously to detect DNA, proteins, metal ions, and DNA-binding molecules. Others have used gold nanoparticles and electrochemical approaches to evaluate enzymatic activity. To our knowledge, we report the first example of the use of DNA-AuNPs as colorimetric indicators to evaluate enzymatic activity and to screen enzyme inhibitors. In principle, this method can be used to screen libraries of inhibitors of endonucleases in a highthroughput fashion by using either the naked eye or a simple colorimetric reader. Probes were prepared by functionalizing two separate batches of 13-nm gold particles with two different thiolmodified oligonucleotide strands, DNA-1 (5’-CTCCCTAATAACAATTTATAACTATTCCTA-A10-SH-3’) and DNA-2 (5’-TAGGAATAGTTATAAATTGTTATTAGGGAG-A10SH-3’). These functionalized particles are denoted DNAAuNP-1 and DNA-AuNP-2. DNA-1 and DNA-2 are complementary to each other. Therefore, DNA-AuNP-1 and DNA-AuNP-2 can hybridize to form a cross-linked network of nanoparticles, which is purple in color owing to the redshifted plasmon band of the gold nanoparticles (13 nm). This red-shifting is a well-understood process and is a highly diagnostic feature of aggregate formation. These aggregates can then be used as colorimetric indicators of endonuclease activity (Scheme 1). As the endonuclease degrades the DNA-duplex interconnects, particles are released, regenerating a red color due to the dispersed nanoparticles. The color can be observed with the naked eye, or the absorbance (520 nm) can be measured by UV/Vis spectroscopy. The DNA-AuNP aggregates were used to evaluate the enzymatic activity of deoxyribonuclease (DNase) I. In a typical experiment, DNase I, at a predetermined concentration (10, 15, 20, 30, or 40 unitsmL ), was added to a solution of the aggregates. The color of the solution gradually changed from purple to red. By measuring the absorbance at 520 nm, we could quantitatively follow the nucleic acid hydrolysis catalyzed by DNase I (Figure 1 a). The reaction rate increases with increasing enzyme concentration and can be followed in real time. In addition to screening enzyme activity, one can easily use the assay to evaluate the efficiency of inhibitors of DNase I. In a typical screening experiment, DNase I (15 unitsmL ) was added to solutions of the DNA-AuNP aggregates in the presence of one of the following DNAbinding molecules (1 mm): amsacrine (AMSA), anthraquinone-2-carboxylic acid (AQ2A), 9-aminoacridine (9-AA), ellipticine (EIPT), daunorubicin (DNR), ethidium bromide (EB), or 4’,6-diamidino-2-phenylindole (DAPI). These DNAbinding molecules are known to inhibit DNase I. 12] The absorbance at 520 nm was monitored as a function of time (sample scan rate= 5 min ; Figure 1b), and the color of the solution was followed with the naked eye (Figure 2). The time [*] X. Xu, Dr. M. S. Han, [+] Prof. C. A. Mirkin Department of Chemistry and International Institute for Nanotechnology Northwestern University 2145 Sheridan Road, Evanston, IL 60208-3113 (USA) Fax: (+1)847-467-5123 E-mail: chadnano@northwestern.edu [] Current address: Department of Chemistry, Chung-Ang University Seoul 156-765, Korea [] These authors equally contributed to this work.

Dopamine genes and reward dependence in adolescents with excessive internet video game play.

Abstract: :Excessive internet video game play (EIGP) has emerged as a leading cause of behavioral and developmental problems in adolescents. Recent research has implicated the role of striatal dopaminergic system in the behavioral maladaptations associated with EIGP. This study investigates the reward

Revealing the bifurcation in the unfolding pathways of GFP by using single-molecule experiments and simulations

Abstract: Nanomanipulation of biomolecules by using single-molecule methods and computer simulations has made it possible to visualize the energy landscape of biomolecules and the structures that are sampled during the folding process. We use simulations and single-molecule force spectroscopy to map the complex energy landscape of GFP that is used as a marker in cell biology and biotechnology. By engineering internal disulfide bonds at selected positions in the GFP structure, mechanical unfolding routes are precisely controlled, thus allowing us to infer features of the energy landscape of the wild-type GFP. To elucidate the structures of the unfolding pathways and reveal the multiple unfolding routes, the experimental results are complemented with simulations of a self-organized polymer (SOP) model of GFP. The SOP representation of proteins, which is a coarse-grained description of biomolecules, allows us to perform forced-induced simulations at loading rates and time scales that closely match those used in atomic force microscopy experiments. By using the combined approach, we show that forced unfolding of GFP involves a bifurcation in the pathways to the stretched state. After detachment of an N-terminal α-helix, unfolding proceeds along two distinct pathways. In the dominant pathway, unfolding starts from the detachment of the primary N-terminal β-strand, while in the minor pathway rupture of the last, C-terminal β-strand initiates the unfolding process. The combined approach has allowed us to map the features of the complex energy landscape of GFP including a characterization of the structures, albeit at a coarse-grained level, of the three metastable intermediates.

Development and scale effects of small Swiss-roll combustors

Abstract: The configuration of Swiss-roll was adopted as a promising structure for the development of sub-millimetre scale combustors. In this study, the scaling effects are investigated both experimentally and analytically. Based on our first proto-type (64 mm in diameter), scaled-down combustors (45 mm) with different design parameters were fabricated; diameter of the combustor, top plate thickness, channel size and combustor material. A simple one-dimensional analytical model was constructed to interpret the combustion characteristics of the Swiss-roll combustors. Two energy equations for combustor body and mixture, along with species equations employing two-step global reaction model were solved. In spite of the simplicity of the present model, important characteristics of the combustors such as upper and lower flammability limits, effect of cap thickness on flammability limits were predicted well. Based on the analytical results, several smaller coin-size combustors (diameter 26 and 20 mm) were additionally developed and their characteristics were investigated. This study shows that the effects of design parameters are important in the practical development of smaller combustors.

Cyclams bearing diametrically disubstituted pyrenes as Cu2+- and Hg2+-selective fluoroionophores.

Abstract: New cyclam derivatives having diametrically disubstituted pyrene fluorophores were prepared and their fluoroionophoric properties toward transition metal ions were investigated. The compounds exhibited significant selectivity toward Hg2+ and Cu2+ ions in switching-off type responses in aqueous methanol or acetonitrile solution. Dipyrene-diamide derivative 3, having extra binding sites of the amide function, exhibited more pronounced chemosensing behavior toward Hg2+ and Cu2+ ions than its parent, dipyrene derivative 2. Detection limits for the analysis of Hg2+ and Cu2+ ions of dipyrene-diamide derivative 3 were 1.45 × 10-6 and 1.30 × 10-6 M, respectively. The diametrically disubstituted dipyrene-cyclam 2 may be utilized as a new starting platform for the design of other supramolecular fluorescent signaling systems having switching or chemosensing behaviors toward transition metal ions.

Hybrid Flexible Neural-Tree-Based Intrusion Detection Systems

Abstract: An intrusion is defined as a violation of the security policy of the system, and, hence, intrusion detection mainly refers to the mechanisms that are developed to detect violations of system security policy. Current intrusion detection systems ~IDS! examine all data features to detect intrusion or misuse patterns. Some of the features may be redundant or contribute little ~if anything! to the detection process. The purpose of this study is to identify important input features in building an IDS that is computationally efficient and effective. This article proposes an IDS model based on a general and enhanced flexible neural tree ~FNT!. Based on the predefined instruction/operator sets, a flexible neural tree model can be created and evolved. This framework allows input variables selection, overlayer connections, and different activation functions for the various nodes involved. The FNT structure is developed using an evolutionary algorithm, and the parameters are optimized by a particle swarm optimization algorithm. Empirical results indicate that the proposed method is efficient. © 2007 Wiley Periodicals, Inc.

Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin.

Abstract: The effects of quercetin and rutin on the asthmatic responses were studied in ovalbumin (OA)-sensitized conscious guinea pigs challenged with aerosolized-OA. We measured the specific airway resistance (sRaw) in the double-chambered plethysmograph during the immediate-phase response (IAR) and late-phase response (LAR) at 3 approximately 10 min and 24 hr after OA challenge, respectively. We counted leukocytes in bronchoalveolar lavage fluid (BALF) using Wright's stain, as well as in lung tissue fixed with 10% formalin and stained with H & E stain. Quercetin and rutin (7.5 mg/kg, p.o.) significantly and dose-dependently inhibited both sRaw on IAR (31.60 and 26.44%) and LAR (29.87 and 28.69%) but with less efficacy than dexamethasone (3 mg/kg) and salbutamol (0.3 mg/kg), which inhibited IAR by 36.71 and 69.45%, and LAR by 67.23 and 0%, respectively, Quercetin and rutin (15 mg/kg) also inhibited production of histamine, PLA2, and EPO, and recruitment of leukocytes, particularly neutrophils and eosinophils, during LAR. respectively. Dexamethasone (3 mg/kg) also significantly reduced the recruitment of neutrophils, eosinophils, and lymphocytes in BALF, and salbutamol (0.3 mg/kg) reduced neutrophils and eosinophils with lower activity than dexamethasone. These results indicate that quercetin and rutin may be useful in the treatment of IAR and LAR in asthma via inhibition of histamine release, PLA2, and EPO, and reduced recruitment of neutrophils and eosinophils into the lung.

A new classification of pattern hair loss that is universal for men and women: Basic and specific (BASP) classification

Abstract: Background Pattern hair loss (PHL) can be classified into several patterns. Currently, the Hamilton–Norwood classification system for men and the Ludwig grade system for women are commonly used to describe patterns of hair loss. However, these pre-existing classifications have some limitations. Objective To establish an acceptable, universal, and accurate standard of both male and female pattern hair loss and to report its use in determining the incidence of PHL. Methods We developed a new classification system (BASP classification) and then applied this system to classify the types of PHL. The BASP classification was based on observed patterns of hair loss. The basic (BA) types represent the shape of the anterior hairline, and the specific types (SP) represent the density of hair on distinct areas (frontal and vertex). There are four basic types (L, M, C, and U) and two specific types (F and V). The final type is decided by the combination of the assigned basic and specific types. Between November 2004 and June 2005, 2213 Korean subjects, comprised of 1768 males and 445 females, were classified according to the BASP classification at 13 university dermatologic centers nationwide throughout South Korea, as a multicenter study of the Korean Hair Research Society. Results For both sexes, the majority of patients enrolled in the study were in the third and fourth decade of life (65.1% of males and 56.68% of females). In males, the older group as well as the younger group in the study were more likely to have little recession of the frontal hairline (classified as type M1∼2) and diffuse thinning over the top of scalp (type F1∼2). The women in the study developed typical female PHL. Limitations The subjects of our study were mostly outpatients and some inpatients who complained about hair loss, not the general population of Korea. Conclusion The BASP classification is a new stepwise, systematic, and universal classification system for PHL, regardless of sex.

Social Class and Earnings Inequality

Abstract: The authors examine whether growth in earnings inequality has played out in ways that are class strengthening or class weakening. Using the Current Population Survey, they show that the absolute amount of inequality is increasing (a) between big classes, (b) between the occupations constituting big classes, and (c) within occupations. In relative terms, the share of total inequality occurring within occupations has declined, whereas the share of total inequality occurring between classes and between the occupations constituting big classes has tended to increase, most clearly for men. Although the majority of earnings inequality is still generated within occupations, especially rapid growth of the between-class and between-occupation components implies that the well-known takeoff in inequality has generated a “lumpier” earnings distribution with relatively stronger class and occupational distinctions.

Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention

Abstract: Background and study aims Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention. Patients and methods Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention. Results Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage. Conclusions Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.

The mutation of the Toyota Production System: adapting the TPS at Hyundai Motor Company

Abstract: This paper examines the spread of Toyota Production System (TPS) through Korea, by focusing on the experience of Hyundai Motor Company. Drawing upon data obtained from field research, this case study interprets the adoption of TPS from an evolutionary perspective, arguing that the emulation of TPS should not entail adopting TPS as Toyota developed it originally, but to develop one's own production model. Over the past 40 years, Hyundai has developed its own production model, Hyundai Production System (HPS), initially emulating TPS, followed by re-interpreting and modifying TPS to adapt to the company's unique circumstances. HPS is a mutated form of TPS. The Hyundai case reveals that the adoption of TPS involves a complex evolutionary process of organizational learning and interpretation. This case sheds light on the possibility of various paths toward lean production, and demonstrates that both external and internal factors combine to form a complicated causal chain, influencing the ‘mutated’ emulation of...

Postoperative changes in paraspinal muscle volume: comparison between paramedian interfascial and midline approaches for lumbar fusion

Abstract: In this study, we compared the paramedian interfascial approach (PIA) and the traditional midline approach (MA) for lumbar fusion to determine which approach resulted in the least amount of postoperative back muscle atrophy. We performed unilateral transforaminal posterior lumbar interbody fusion via MA on the symptomatic side and pedicle screw fixation via PIA on the other side in the same patient. We evaluated the damage to the paraspinal muscle after MA and PIA by measuring the preoperative and postoperative paraspinal muscle volume in 26 patients. The preoperative and postoperative cross-sectional area, thickness, and width of the multifidus muscle were measured by computed tomography. The degree of postoperative paraspinal muscle atrophy was significantly greater on the MA side than on the contralateral PIA side (-20.7% and -4.8%, respectively, p<0.01). In conclusion, the PIA for lumbar fusion yielded successful outcomes for the preservation of paraspinal muscle in these 26 patients. We suggest that the success of PIA is due to less manipulation and retraction of the paraspinal muscle and further studies on this technique may help confirm whether less muscle injury has positive effects on the long-term clinical outcome.

Density-Induced Support Vector Data Description

Abstract: The purpose of data description is to give a compact description of the target data that represents most of its characteristics. In a support vector data description (SVDD), the compact description of target data is given in a hyperspherical model, which is determined by a small portion of data called support vectors. Despite the usefulness of the conventional SVDD, however, it may not identify the optimal solution of target description especially when the support vectors do not have the overall characteristics of the target data. To address the issue in SVDD methodology, we propose a new SVDD by introducing new distance measurements based on the notion of a relative density degree for each data point in order to reflect the distribution of a given data set. Moreover, for a real application, we extend the proposed method for the protein localization prediction problem which is a multiclass and multilabel problem. Experiments with various real data sets show promising results

Potentiation of the NMDA Receptor in the Treatment of Schizophrenia: Focused on the Glycine Site

Abstract: N-methyl-d-aspartate receptor (NMDAR) hypo-function theory of schizophrenia proposes that impairment in NMDAR function be associated with the pathophysiology of schizophrenia and suggests that enhancement of the receptor function may produce efficacy for schizophrenia. Consistent with this theory, for the last decade, clinical trials have demonstrated that the enhancement of NMDAR function by potentiating the glycine site of the receptor is efficacious in the treatment of schizophrenia. Full agonists of the glycine site, glycine and d-serine and a glycine transporter-1 inhibitor, sarcosine, added to antipsychotic drugs, have been shown to be effective in the treatment of negative symptoms and possibly cognitive symptoms without significantly affecting the positive symptoms of schizophrenia. A partial agonist of the glycine site, d-cycloserine, added to antipsychotic drugs, can be effective for the negative symptoms at the therapeutic doses. However, these drugs have not shown clinical efficacy when added to clozapine, suggesting that the interactions of clozapine and the glycine site potentiators may be different from those of other antipsychotic drugs and the potentiators. This article suggests that the glycine site potentiators may produce efficacy for negative and cognitive symptoms by blocking apoptosis-like neuropathological processes in patients with chronic schizophrenia and thereby can deter progressive deterioration of the disorder. This article proposes a polypharmacy of glycine site potentiators augmented with antipsychotic drugs to control positive and negative symptoms in a synergistic manner and block deterioration in schizophrenia. Since the NMDAR complex consists of multiple sites modulating receptor functions, the efficacy of glycine site potentiators for schizophrenia suggests the possibility that manipulation of other modulating sites of the NMDAR can also be efficacious in the treatment of schizophrenia.

Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: Comprehensive study of clinical and immunohistochemical findings in younger Asian patients

Abstract: Background and Aims: The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to severe steatohepatitis (NASH). The aim of our study was to identify clinical predictors distinguishing NASH from steatosis and to study the pathogenesis of NASH in a young Korean population. Methods: Clinical and biochemical variables from 39 biopsied NAFLD patients were retrospectively analyzed. All liver biopsy specimens were immunohistochemically examined for Kupffer cells (CD68, CD14), as well as expression of tumor necrosis factor-alpha (TNF-α) and mitochondrial uncoupling protein 2 (UCP-2). Results: There were no significant differences in serum biochemistry between the two groups (15 steatosis vs 24 NASH). There was a significant difference between the body mass index (BMI) values (kg/m2) of the NASH (28.4 ± 3.4 kg/m2) and steatosis (25.8 ± 2.8 kg/m2) patients (P < 0.025), with a BMI of 28.9 kg/m2 representing the best threshold for distinguishing NASH from steatosis patients. BMI was significantly related to the degree of fibrosis (P < 0.01). CD68+ Kupffer cells were more common in the livers of NASH patients (P < 0.05), and TNF-α and UCP-2 were expressed in all NASH specimens and were related with the severity of inflammation and fibrosis (P < 0.05). Conclusions: BMI could be used to distinguish NASH from steatosis in younger Korean patients. A high BMI with a low alanine aminotransferase (ALT) value tended to suggest the presence of severe fibrosis in NASH, while the number of CD68+ Kupffer cells and the staining intensity of TNF-α and UCP-2 were correlated with general pathologic severity in patients with NAFLD.