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Purpose To evaluate histogram and texture parameters on pretreatment dynamic contrast material-enhanced (DCE) magnetic resonance (MR) images in lung cancer in terms of temporal change, optimal time for analysis, and prognostic potential. Materials and Methods This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Thirty-eight patients with pathologically proved lung cancer undergoing standard pretreatment DCE MR imaging were included. A fat-suppressed, T1-weighted, volume-interpolated breath-hold MR sequence was performed every 30 seconds for 300 and 480 seconds after contrast material administration. A region of interest was manually drawn in the largest cross-sectional area of the tumor on DCE MR images to extract semiquantitative perfusion, histogram, and texture parameters. Predictability of 2-year progression-free survival (PFS) was analyzed by using the Kaplan-Meier method and Cox regression analysis. Results MR histogram and texture parameters increased rapidly 30-60 seconds after contrast material administration. Standard deviation and entropy then plateaued, whereas skewness and kurtosis rapidly decreased. Univariate Cox regression analysis revealed that standard deviation and entropy were significant predictors of survival; their statistical significance was preserved from 60 to 300 seconds, with the smallest P values (P ≤ .001) occurring from 120 to 180 seconds. At multivariate Cox regression analysis, entropy was the sole significant predictor of 2-year PFS (hazard ratio at 180 seconds, 10.098 [95% confidence interval: 1.579, 64.577], P = .015; hazard ratio at 120 seconds: 11.202 [95% confidence interval: 1.761, 71.260], P = .010). Conclusion Histogram and texture parameter changes varied after contrast material injection. The 120-180-second window after contrast material injection was optimal for MR imaging-derived texture parameter and entropy at DCE MR imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic INMDA in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg(2+) artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in Iho lding (IGLU) at a holding potential (Vholding) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive IGLU was observed even in normal aCSF at Vholding of -40 mV or -20 mV. IGLU was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in Iholding (IAMPA) in SON MNCs. Pretreatment with AP5 attenuated IAMPA amplitudes to ~60% of the control levels in low-Mg(2+) aCSF, but not in normal aCSF at Vholding of -70 mV. IAMPA attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced IAMPA attenuation in SON MNCs. Finally, chronic dehydration did not affect IAMPA attenuation by AP5 in the neurons. These results suggest that tonic INMDA, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.

Axon regeneration after injury in the central nervous system is hampered in part because if an age-dependent decline in the intrinsic axon growth potential, and one of the strategies to stimulate axon growth in injured neurons involves pharmacological manipulation of implicated signaling pathways. Here we report phenotypic cell-based screen of chemical libraries and structure-activity-guided optimization that resulted in the identification of compound 7p which promotes neurite outgrowth of cultured primary neurons derived from the hippocampus, cerebral cortex, and retina. In an animal model of optic nerve injury, compound 7p was shown to induce growth of GAP-43 positive axons, indicating that the in vitro neurite outgrowth activity of compound 7p translates into stimulation of axon regeneration in vivo. Further optimization of compound 7p and elucidation of the mechanisms by which it elicits axon regeneration in vivo will provide a rational basis for future efforts to enhance treatment strategies.

Postischemic brain damage in stroke is proceded with complicated pathological events, and so multimodal drug treatments may offer better therapeutic means for improving clinical outcomes. Here, we report robust neuroprotective effects of a novel compound, 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a 2-hydroxy-4-trifluoromethyl benzoic acid (HTB, a metabolite of triflusal)-pyruvate ester. Intravenous administration of OPTBA (5 mg/kg) 3 or 6 h after middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats reduced infarct volumes to 38.5 ± 11.4% and 46.5 ± 15.3%, respectively, of that of MCAO controls, and ameliorated motor impairment and neurological deficits. Importantly, neuroprotective effects of OPTBA were far greater than those afforded by combined treatment of HTB and pyruvate. Furthermore, OPTBA suppressed microglial activation and proinflammatory cytokine inductions more effectively than HTB/pyruvate co-treatment in the postischemic brain and LPS-treated cortical slice cultures and also attenuated NMDA-induced neuronal death in hippocampal slice cultures. LC-MS analysis demonstrated that OPTBA was hydrolyzed to HTB and pyruvate with a t1/2 of 38.6 min in blood and 7.2 and 2.4 h in cortex and striatum, respectively, and HTB was maintained for more than 24 h both in blood and brain tissue. Together these results indicate OPTBA acts directly and via its hydrolysis products, thus acting as a multimodal neuroprotectant in the postischemic brain.

A non-enzymatic biosensor was developed using boron-doped nanocrystalline diamond (BDND) based on a Cu electrode with Cu(OH) 2 dendritic architecture. The Cu(OH) 2 nanoflower electrode was covered with a BDND layer using an electrostatic self-assembly seeding method with nanodiamond particles and hot-filament chemical vapor deposition. X-ray diffraction and Raman spectral analysis confirmed that the BDND nanoflower electrode was synthesized onto Cu(OH) 2 nanoflowers. Field-emission scanning electron microscope images showed that the fabricated electrodes were nanoflowers possessing large surface areas. From cyclic voltammetry, the peak currents of an BDND/Cu(OH) 2 /Cu electrode was about 7, 6.2, and 5.9 times higher than that of the Cu foil, Cu(OH) 2 /Cu, and BDND/Cu electrodes, respectively. A biosensor based on BDND/Cu(OH) 2 /Cu exhibited excellent performance for glucose detection, and it had a linear detection range of 0 to 6 mM, a correlation coefficient of 0.9994, a low detection limit of 9 μM, and a high sensitivity of 2.1592 mA mM − 1 cm − 1 .

Purpose: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. Methods: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). Results: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P ＜ 0.034). Chemoradiation appeared to improve overall survival (P ＜ 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. Conclusion: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.

We consider a model estimation and model selection methods for the multi-way contingency table data with non-response or missing values. We also consider hierarchical Bayesian model in order to handle a boundary solution problem that can happen in the maximum likelihood estimation under non-ignorable non-response model and we deal with a model selection method to find the best model for the data. We utilized Bayes factors to handle model selection problem under Bayesian approach. We applied proposed method to the pre-election survey for the 2004 Korean National Assembly race. As a result, we got the non-ignorable non-response model was favored and the variable of voting intention was most suitable.

Background The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria. Methods 117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS). Results Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/µL, 12,000/µL, and 0.39%, respectively. In multivariate analyses, ANC

This study estimated the population pharmacokinetics of risperidone and its active metabolite, 9-hydroxyrisperidone, according to genetic polymorphisms in the metabolizing enzyme (CYP2D6) and transporter (ABCB1) genes in healthy subjects. Eighty healthy subjects who received a single oral dose of 2 mg risperidone participated in this study. However, eight subjects with rare genotype variants in CYP2D6 alleles were excluded from the final model built in this study. We conducted the population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2D6 alleles and ABCB1 (2677GT/A and 3435CT) on the population pharmacokinetics of risperidone and 9-hydroxyrisperidone. A two-compartment model with a first-order absorption and lag time fitted well to serum concentration-time curve for risperidone. 9-hydroxyrisperidone was well described by a one-compartment model as an extension of the parent drug (risperidone) model with first-order elimination and absorption partially from the depot. Significant covariates for risperidone clearance were genetic polymorphisms of CYP2D6*10, including CYP2D6*1/*10 (27.5 % decrease) and CYP2D6*10/*10 (63.8 % decrease). There was significant difference in the absorption rate constant (k ( a )) of risperidone among the CYP2D6*10 genotype groups. In addition, combined ABCB1 3435CT and CYP2D6*10 genotypes had a significant (P 0.01) effect on the fraction of metabolite absorbed from the depot. The population pharmacokinetic model of risperidone and 9-hydroxyrisperidone including the genetic polymorphisms of CYP2D6*10 and ABCB1 3435CT as covariates was successfully constructed. The estimated contribution of genetic polymorphisms in CYP2D6*10 and ABCB1 3435CT to population pharmacokinetics of risperidone and 9-hydroxyrisperidone suggests the interplay of CYP2D6 and ABCB1 on the pharmacokinetics of risperidone and 9-hydroxyrisperidone according to genetic polymorphisms.

Diclofenac has been of environmental concern due to the potential harmful effects on non-target organisms at environmentally relevant concentrations. In this study, we evaluated the transformation kinetics of diclofenac and its two major metabolites in two laboratory-scale experiments: the transformation of diclofenac in the presence of rat liver S9 fraction with co-factors, and the transformation of diclofenac, 4'-hydroxy-diclofenac and diclofenac β-O-acyl glucuronide in the inoculum used for the OECD 301C ready-biodegradability test. 4'-Hydroxy-diclofenac was identified as the major phase I metabolite and diclofenac β-O-acyl glucuronide was identified as the major phase II metabolite in the S9 assay. Transformation of diclofenac in the microbial degradation test did not occur significantly for 28 d, whereas 4'-hydroxy-diclofenac degraded slowly, indicating that the biological removal of diclofenac is not likely to occur in conventional STPs unless sorptive removal is significant. However, diclofenac β-O-acyl glucuronide deconjugated to form equimolar diclofenac within 7 d, in the microbial degradation test. The mixture of diclofenac and its two metabolites, formed after incubating diclofenac in S9 medium for 2 h, was spiked in the inoculum to link both assays. The concentrations of diclofenac and its metabolites, measured over time, agreed well with predicted values, using rate parameters obtained from independent experiments. The results show that phase II metabolites generated in mammals may deconjugate easily in conventional STPs to form a parent compound and that these processes should be considered during the environmental monitoring and risk assessment of diclofenac.

Long-chain branched-polypropylene (LCB-PP) was prepared by melt grafting, and LCB-PP/silicate composites were prepared by adding 1–7 wt% silicate using a mini-compounder at 190 °C. The chemical structure of the LCB-PP was confirmed by the existence of a –C=C–H-stretching peak at 3100, cm−1 in the Fourier transform infrared spectrum. LCB-PP and the LCB-PP/silicate composites exhibited unusual rheological properties, including high shear-thinning tendency and elasticity. Shear-thinning tendency and elasticity were highest in the composite containing 5 wt% silicate. These effects were confirmed by oscillatory rheological measurements. The crystallization behavior of LCB-PP and the silicate composite were investigated using a non-isothermal process proposed by Ozawa. The exothermic pattern of the composite is narrower and sharper than those of PP and branched PP. The extending exponents were 3.6 for PP, 2.4 for LCB-PP and 1.5 for the composite. These behaviors can be interpreted by speculating that the silicate in the PP matrix functions as a seed for crystallization and alters the crystallization process. The slopes of G″–G′ decreased to 1.21 for the long-chain branched-polypropylene (LCB-PP) and 1.07 for PP-F07-S5. A decreased slope indicates an increase in elasticity, shear thinning effect and melt strength. The extending Avrami analysis proposed by Ozawa applied to PP, LCP-PP and the composite. The exponents were 3.6 for PP, 2.4 for LCB-PP and 1.5 for the composite.

Branched polypropylenes (PP) with long chain branch were prepared by solid state reaction with three different branching agent of 0.3 wt% content. The chemical structures, non-isothermal crystallization behavior and complex viscosity of the branched PP were investigated by FTIR, DSC, optical microscope, and dynamic rheological measurement. The chemical structure of the branched PP was confirmed by the existence of =C-H stretching peak of the branching agent at 3100 . There was no distinct change in melting temperature in case of PP-D-0-3 and PP-F-0-3, but PP-H-0-3 indicated a decrease in melting temperature. The decrease in melting temperature was interpreted by the fact that the degradation reaction of PP was more dominant than branched reaction, and confirmed by a decrease in complex viscosity. The non-isothermal crystallization behavior of the branched PP was analyzed using by Avrami equation. The Avrami exponent of PP was 3, and the values of the branched PP with DVB and FS were below 3. The activation energy of PP calculated by Kissinger method was 25 kJ/mol, and there were no big difference in activation energies of the branched PPs compared to PP.

Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors.We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through June 2015. Randomized controlled trials published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between SGLT2i/INS and DPP4i/INS indirectly with covariates adjustment. Risk of potential bias was assessed.Fourteen eligible randomized controlled trials comprising 6980 patients were included (five SGLT2 inhibitor studies and nine DPP4 inhibitor studies). Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbASodium glucose cotransporter 2 inhibitors achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin. There has been no direct comparison of SGLT2 inhibitors and DPP4 inhibitors in patients with T2DM inadequately controlled with insulin therapy. In this study, we performed indirect meta-analysis comparing SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy. Without increasing hypoglycaemia, SGLT2 inhibitors showed better glycaemic control and greater weight reduction than DPP4 inhibitors in patients with T2DM inadequately controlled with insulin. The results of the current study could serve as the best available evidence in selecting oral agents to improve glycaemic control in insulin-treated T2DM patients. Copyright © 2016 John WileySons, Ltd.

Purpose Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin. Materials and Methods CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals. Results Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival. Conclusion The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.

Background and aim: Limited studies on the relationships between epidermal growth factor receptor (EGFR) expression and the grades of phyllodes tumors (PT) of the breast were reported. This study evaluated the significance of EGFR overexpression in the grading of PT. Methods: Immunohistochemical stain for EGFR was done in 46 PT cases. The differences of EGFR expression according to the degrees of cytologic atypia and mitotic count and between benign, borderline and malignant PTs based on Rosen or World Health Organization (WHO) criteria were analyzed. Results: Significant differences of positive (moderate membranous and cytoplasmic, more than 10% of tumor cells) and strong positive (moderate more than 50% of tumor cells) reactions for EGFR were found according to the degree of cytologic atypia (P= 0.0016 and P= 0.0122) and between the PTs showing ≤5 mitoses and >5 mitoses/10 high power field (P= 0.0230 and P= 0.0058). Positive reaction for EGFR was more common in borderline/malignant PTs than benign PTs, and strong positive reaction for EGFR was relatively common in malignant PTs. Conclusions: Epidermal growth factor receptor overexpression, more than 10% of tumor cells, could be used as an ancillary tool for the discrimination of benign from borderline and malignant PTs.

Cationic liposomes have been actively used as gene delivery vehicle because of their minimal toxicity, but their relatively low efficiency of gene delivery is the major disadvantage of these vectors. Recently, cysteine residue incorporation to HIV-1 Tat peptide increased liposomemediated transfection compared with unmodified Tat peptide. Therefore, we designed a novel modified Tat peptide having a homodimeric (Tat-CTHD, Tat-NTHD) and closed structure (cyclic Tat) simply by using the disulfide bond between cysteines to develop a more efficient and safe nonviral gene delivery system. The mixing of Tat-CTHD and Tat-NTHD with DNA before mixing with lipofectamine increased the transfection efficiency compared with unmodified Tat peptide and lipofectamine only in MCF-7 breast cancer cells and rat vascular smooth muscle cells. However, cyclic Tat did not show any improvement in the transfection efficiency. In the gel retardation assay, Tat-CTHD and Tat-NTHD showed more strong binding with DNA than unmodified Tat and cyclic Tat peptide. This enhancement was only shown when Tat-CTHD and Tat-NTHD were mixed with DNA before mixing with lipofectamine. The effects of Tat- CTHD and Tat-NTHD were also valid in the experiment using DOTAP and DMRIE instead of lipofectamine. We could not find any significant cytotoxicity in the working concentration and more usage of these peptides. In conclusion, we have designed a novel transfection-enhancing peptide by easy homodimerization of Tat peptide, and the simple mix of these novel peptides with DNA increased the gene transfer of cationic lipids more efficiently with no additional cytotoxicity.

Background: The Glidescope Videolaryngoscope (GVL) is a newly developed video laryngoscope. It offers a significantly improved laryngeal view and facilitates endotracheal intubation in difficult airways, but it is controversial in that it offers an improved laryngeal view in normal airways as well. And the price of GVL is expensive. We hypothesized that intubation carried out by fully experienced anesthesiologists using the GVL with appropriate pre-anesthetic preparations offers an improved laryngeal view and shortened intubation time in normal airways. Therefore, the aim of this study was to compare the GVL with the Macintosh laryngoscope in normal airways and to determine whether GVL can substitute the Macintosh laryngoscope. Methods: This study included 60 patients with an ASA physical status of class 1 or 2 requiring tracheal intubation for elective surgery. All patients were randomly allocated into two groups, GVL (group G) or Macintosh (group M). ADS (airway difficulty score) was recorded before induction of anesthesia. The anesthesiologist scored vocal cord visualization using the percentage of glottic opening (POGO) visible and the subjective ease of intubation on a visual analogue scale (VAS). The time required to intubate was recorded by an assistant. Results: There was a significant increase in POGO when using the GVL (P < 0.05). However, there was no difference in the time required for a successful tracheal intubation using the GVL compared with the Macintosh laryngoscope. The VAS score on the ease of intubation was significantly lower for the GVL than for the Macintosh laryngoscope (P < 0.05). Conclusions: GVL could be a first-line tool in normal airways. (Korean J Anesthesiol 2011; 60: 339-343)

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic (DA) neurons. Mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) exhibit microglial activation-induced oxidative stress and inflammation, and nigrostriatal DA neuronal damage, and thus serve as an experimental model of PD. Here, we report that fluoxetine, one of the most commonly prescribed antidepressants, prevents MPTP-induced degeneration of nigrostriatal DA neurons and increases striatal dopamine levels with the partial motor recovery. This was accompanied by inhibiting transient expression of proinflammatory cytokines and inducible nitric oxide synthase; and attenuating microglial NADPH oxidase activation, reactive oxygen species/reactive nitrogen species production, and consequent oxidative damage. Interestingly, fluoxetine was found to protect DA neuronal damage from 1-methyl-4-phenyl-pyridinium (MPP(+)) neurotoxicity in co-cultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present in vivo and in vitro findings show that fluoxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress. Therefore, we carefully propose that neuroprotection of fluoxetine might be associated with its anti-inflammatory properties and could be employed as novel therapeutic agents for PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

Ethyl pyruvate (EP) is known as a scavenger of reactive oxygen species (ROS) in the body through its role in the donation of diketone groups to metals to form an EP-metal complex. In order to develop a method for the quantification of EP in biological media, a sensitive and specific, high-performance liquid chromatographyelectrospray ionization-mass spectrometry (HPLC-ESI/MS) method is used to determine the EP-alkali metal ion binding species. The analyte was separated on a ZORBOX SB-C8 (3.5 µm, 30 mm × 2.1 mm I.D.) column and analyzed in selected ion monitoring (SIM) mode with a positive ESI interface using the m/z 255 [2M + Na] + ion. The method was validated over the concentration range of 0.5-60.0 µg/mL under 1/9 (v/v) of acetonitrile/methanol solvent system with flow rate 0.05 mL/min. The limit of quantification (LOQ) was 0.5 µg/mL.

The purpose of this study is to investigate the usefulness and application of home economics curriculum to housewives. For this research, a survey was conducted using questionnaires against 427 housewives living in Seoul, Gyeonggi-do, and other provinces. The data analysis of this study was verified by frequency, mean, t-test, and Cronbach's coefficient by using SPSS 12.0 program. The conclusions of this study are as follows. First, more than 88% of the housewives recognize that home economics curriculum is necessary. Second, as for the areas of the usefulness and application of home economics curriculum, housewives recognize the "family and child" area was most useful, followed by "food, nutrition & cookery", "consumer and family financial management", "housing and residential interior design", and "clothing care, apparel design and making" areas. Third, the better perceive the housewives think of the home economics curriculum, the higher is the appreciation of the curriculum. Based on this research, home economics curriculum was proved very important and necessary in everyday life for housewives.

A series of fluoxetine, where the N-methylamino group was replaced and then simplified, were synthesized and their inhibitory effect was tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. Although the synthesized compounds generally revealed weaker activity or greater cytotoxicity than fluoxetine, compound 10a, in which the N-methylamino group in fluoxetine was replaced by morpholine, and the trifluoromethylphenyl ring was substituted with simple oxo group, suppressed NO production dose-dependently at 10, 20 and 40 µM concentrations with less cytotoxicity than fluoxetine, and inhibited iNOS mRNA and protein expression at the same concentrations in LPS-induced BV2 cells. The results suggested that the trifluoromethylphenyl ring moiety in fluoxetine is not necessary for the suppression of NO production and that 10a has the potential as a potent inhibitor of NO production.

1-2 Among natural antioxidants, caffeic acid, which is found in various agricultural products such as fruits, vegetables, wine, olive oil and coffee beans, has multiple mechanisms involving free radical scavenging, metal ion chel- ation and inhibitory actions on specific enzymes that induce free radicals. 3-4 However, since caffeic acid is not approved for direct use in food, due to its suspected role as a human carcino- gen, based on testing in mice, 5-6 the need has arisen to develop an analogue with similar biological properties. With the goal of finding a new analogue of caffeic acid, we previously reported the synthesis of 1-hydroxy-2-pyridone analogues of caffeic acid by the application of bioisosterism and the evaluation of their antioxidant activities. 7

Non-obstetrical surgery during the first trimester is stressful to both the mother and the fetus. Anesthesiologists are also stressed, not only because of the effects of surgery itself, but also because of the uncertain influences of anesthesia thrown upon on the fetus. The authors present a case of breast surgery successfully performed on a woman 8 weeks pregnant requiring removal of breast abscess by the application of thoracic paravertebral block without any complications. Thoracic paravertebral block may be a safe anesthetic method for non-obstetric surgery during early pregnancy.

Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleural effusion. We report a case of a 53 year-old female patient with cardiac amyloidosis who presented with recurrent accumulation of large pleural effusions. She was initially treated with high dose loop diuretics, but the pleural effusion persisted, with the daily amount of drainage averaging 1 L/day. Accumulation of pleural fluid did not subside after 3 cycles of melphalan/prednisolone therapy. After the introduction of bevacizumab, an anti-VEGF antibody, the amount of pleural effusion decreased significantly. Efficacy of anti-VEGF therapy for refractory pleural effusions needs to be defined through further studies.

The transcriptional feedback circuit, which is at the core of the suprachiasmatic nucleus (SCN) circadian (i.e., 24 h) clock, is tightly coupled to both external entrainment cues, such as light, as well as rhythmic cues that arise on a system-wide level within the SCN. One potential signaling pathway by which these cues are conveyed to the molecular clock is the CREB/CRE transcriptional cascade. In this study, we employed a tetracycline-inducible CREB repressor mouse strain, in which approximately 60% of the SCN neurons express the transgene, to test CREB functionality in the clock and its effects on overt rhythmicity. We show that attenuated CREB signaling in the SCN led to a significant reduction in light-evoked clock entrainment. An examination of circadian timing revealed that CREB repressor mice exhibited normal free-running rhythms in the absence of external lighting cues. However, under conditions of constant light, which typically leads to a lengthening of the circadian period, CREB repressor mice exhibited a dramatic arrhythmic phenotype, which could be reversed with doxycycline. At a cellular level, the repression of CREB led to a significant reduction in both the expression of the circadian clock proteins PERIOD1 and PERIOD2 and the clock output hormones AVP and VIP. Together, these data support the idea that the CRE transcriptional pathway orchestrates transcriptional events that are essential for both the maintenance of SCN timing and light entrainment of the circadian clock.

Cerebral ischemia leads to brain injury via a complex series of pathophysiological events. Therefore, multidrug treatments or multitargeting drug treatments are attractive options in efficiently limiting brain damage. Here, we report a novel multifunctional compound oxopropanoyloxy benzoic acid (OBA-09), a simple ester of pyruvate and salicylic acid. This protective effect was manifested by recoveries from neurological and behavioral deficits. OBA-09 exhibited antioxidative effects in the postischemic brain, which was evidenced by remarkable reduction of lipid peroxidation and 4-hydroxy-2-nonenal staining in OBA-09-administered animals. Reactive oxygen species generation was markedly suppressed in primary cortical cultures under oxygen-glucose deprivation. More interestingly, OBA-09 was capable of scavenging hydroxyl radical in cell-free assays. High-performance liquid chromatography results demonstrated that OBA-09 was hydrolyzed to salicylic acid and pyruvate with t(1/2) = 43 min in serum and 4.2 h in brain parenchyma, indicating that antioxidative function of OBA-09 is executed by itself and also by salicylic acid after the hydrolysis. In addition to antioxidative function, OBA-09 exerts anti-excitotoxic and anti-Zn(2+)-toxic functions, which might be attributed to attenuation of ATP and nicotinamide adenine dinucleotide depletion and to the suppression of nuclear factor-κB activity induction. Together these results indicate that OBA-09 has a potent therapeutic potential as a multimodal neuroprotectant in the postischemic brain and these effects were conferred by OBA-09 itself and subsequently its hydrolyzed products.

Background Anesthesia methods and drugs affect postoperative nausea and vomiting. Propofol is known to have antiemetic effects. We compared the incidence of postoperative vomiting (POV) in children undergoing an adenotonsillectomy; anesthesia in one group was induced with propofol and maintained with sevoflurane and nitrous oxide, and the other group received total intravenous anesthesia (TIVA) with propofol-remifentanil. Methods Ninety children, ASA physical status I, were assigned randomly to one of two groups. In the PSN group, anesthesia was maintained with 2-3 vol% sevoflurane and 50% nitrous oxide. In the PR group, anesthesia was maintained with 10 mg/kg/h propofol and 0.25 µg/kg/min remifentanil. In both groups, anesthesia was induced with 0.5 µg/kg remifentanil and 2 mg/kg propofol. The incidence of POV and the need for rescue antiemetics were assessed in the postanesthesia care unit at 6, 12, and 24 hours postoperatively. Results The total incidence of POV was not significantly different between the groups; POV occurred in eight (17.7%) and three (6.7%) children in the PSN and PR groups, respectively. Postoperative frequency of retching in the recovery room was significantly higher in the PSN group, with four children (8.9%) in the PSN group compared to none (0%) in the PR group (P = 0.041). The frequency of POV 24 hrs after exiting the recovery room tended to be higher in the PSN group than the PR group, but no statistically significant difference was observed. Conclusions If the development of POV in the early anesthetic recovery phase of children undergoing adenotonsillectomy is adequately prevented, propofol-induced anesthesia maintained with sevoflurane-nitrous oxide is as safe as TIVA with propofol-remifentanil.

Purpose: This report describes the results of a survey of the characteristics of pertussis in children from a single institution and com pares it to data from the Korea Centers of Disease Control (KCDC). Methods: We retrospectively evaluated the medical records of 17 and 6 patients diagnosed with pertussis and parapertussis, re spectively, at Soonchunhyang University Bucheon Hospital from January 2005 to January 2017. Results: Of the 17 patients with pertussis, 9 were under 1 year of age (52.9%), 3 were aged between 1 and 10 years (17.6%), and 5 were over 10 years of age (29.4%). Seven patients (41.2%) had never received diphtheria-tetanus-acellular pertussis vaccines, of which 5 were infants below 2 months of age and 2 were 10 years old and lived in China. Four patients showed the initial symptoms of cough in China. The sources of infection were the parents (2 cases) and the siblings (8 cases). All patients showed prolonged se vere cough and the average duration of cough was 26 days. Severe symptoms, including dyspnea, cyanosis, apnea, and seizures, were observed in the children under 2 months of age. According to the recent 10-year KCDC data, the highest rate of pertussis diag nosis was noted in infants (47.8%), followed by adolescents (18.7%). Six patients with parapertussis also presented with prolonged severe cough without any other severe symptoms. Lymphocytosis was not found, unlike the patients with pertussis. Conclusion: The possibility of pertussis and parapertussis should be considered among patients with prolonged severe cough, es pecially in infants and adolescents. (Allergy Asthma Respir Dis 2018;6:54-61)

Rationale Gastrointestinal subepithelial tumors (SETs) with endoscopic features such as ulceration, a red color change, a peeled mucosal layer, and spontaneous bleeding could have malignant potential. However, we encountered a case of a lipoma that presented features different from the generally known features of gastrointestinal SETs. Therefore, we report an interesting rare case of a terminal ileal giant lipoma with a unique feature of spontaneous peeled ulceration on the surface on endoscopy that caused gastrointestinal bleeding. Patient An 82-year-old woman with a 1-week history of abdominal pain and hematochezia presented to our hospital. Diagnoses Ileocolonoscopy revealed a SET with a peeled surface and erythematous and ulcerative mucosal changes as well as exposed a submucosal mass at the terminal ileum. Macroscopically, the lesion appeared as a yellowish pedunculated polypoid mass measuring 3 × 2 cm with a peeled mucosal ulceration. Histopathological findings revealed a submucosal lipoma of the terminal ileum. Intervention We thought that the endoscopic finding indicated malignant SETs or those with malignant potential rather than benign SETs. Therefore, the patient underwent an elective laparoscopic ileocecectomy. Lessons We encountered a lipoma that did not present with the typical features of gastrointestinal SETs. Our findings suggest that clinicians should consider that benign SETs in the terminal ileum may present with various endoscopic findings similar to those of malignant SETs, which can cause fatal symptoms and signs.

In this study, simultaneous nitrification and denitrification (SND) from synthetic wastewater were performed to evaluate dissolved oxygen(DO) effects on chemical oxygen demand(COD) and nitrogen removal in a single membarne bio-reactor(MBR). DO levels in MBR at Run 1, 2, and 3 were 1.9~2.2, 1.3~1.6, and 0.7~1.0 mg/L, respectively. Experimental results indicated that DO had an important factor to affect COD and total nitrogen(TN) removal. SND were able to be accomplished in the continuous-aeration MBR by controlling ambient DO concentration. It is postulated that, because of the oxygen diffusion limitation, an anoxic micro-zone was formed inside the flocs where the denitrification might occur. From the results of this study, 96% of COD could be removed at DO of 0.7mg/L. At run 2 72.92% of nitrogen was removed by the mechanisms of SND (7.75mg-TN/L in effluent). In this study, SND was successfully occurred in a MBR due to high MLSS that could help to form anoxic zone inside microbial floc at bulk DO concentr-ations of 1.3~1.6mg/L.Key Words

Transport of dopamine (DA) by the dopamine transporter from the synaptic cleft into the presynaptic terminals plays a key role in terminating dopaminergic neurotransmission. The binding of psychostimulants to their recognition sites on the DA transporter leads to an inhibition of DA transport and a subsequent rising of the dopamine contents in the synaptic cleft is ascribed to a mode of psychostimulation. Discovery of dopamine transporter inhibitors would be useful with regard to substituting for cocaine and minimizing its abuse. Recently, a number of fluoxetine analogues were synthesized, especially focusing on the substitution of N-methyl amine group through modifying the structure of the fluoxetine, N-methyl-3-[p-trifluoromethylphenoxy]-3-phenylpropylamine, widely used as an antidepressant. Among them, the pharmacological properties of FD-2, (R)-N-ethanol-3-(4-trifluorophenoxy)-3-phenyl propaneamine and FD-4, N-(R)-3-trifluorophenoxy-3-phenylpropane-imidazole with a higher affinity for the DA transporter were characterized in terms of dopamine transporter inhibition expecting for useful cocaine substitutes. Effects of the compounds on [H(3)]dopamine uptake, [I(125)]RTI-55 binding, and DA transporter-associated currents were examined with the ligand binding assays and voltage clamping technique in human embryonic kidney (HEK)-293 cells where the recombinant human DA transporter (hDAT) was stably expressed. Our results showed that (i) fluoxetine was potent in inhibiting both the uptake of [H(3)]DA (IC(50) = 0.21 +/- 0.032 mM, n = 3) and the [I(125)]RTI-55 binding (IC(50) = 0.23 +/- 0.012 mM, n = 10); (ii) N-methyl amine substituted fluoxetine analogues, FD-2 and FD-4 were equally or more potent than fluoxetine itself in terms of inhibition of [H(3)]DA uptake (IC50 FD-2: 0.077 +/- 0.0032 mM (n = 3); FD-4: 0.26 +/- 0.13 mM (n = 3), inhibition of [I(125)]RTI-55 binding, and reduction in DA transporter-associated currents, suggesting that these analogues could be a new class of dopamine transporter inhibitors.

Since aromatic aldehydes are important intermediates in the chemical, pharmaceutical and cosmetic industries, easy and con-venient synthetic methods to synthesize them have been pur-sued. Among the most widely-used methods are formylation of aromatic compounds and oxidation of primary alcohols. Previ-ous reports describe a variety of formylation reagents, including formyl fluoride HCOF and BF

Organic cation transporters (OCTs) are important for absorption, elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is located in a cluster on chromosome 6 and OCTs are in major organs such as intestine, liver, kidney, brain and placenta. Therefore, expression levels and function of OCTs directly affect plasma levels and intracellular concentrations of drugs and thereby determine therapeutic response. The aim of this study was to investigate the frequency of the SNPs on OCT1 (C181T and C1022T) and OCT2 (G808T) to analyze haplotype frequency in healthy Korean population. Human subjects have been genotyped for OCT1 (C181T for 195 subjects and C1022T for 825 subjects), using polymerase chain reaction-based diagnostic tests (RFLP). And for OCT2 (G808T), a total of 861 subjects have been genotyped, using pyrosequencing method. Haplotype was statistically inferred using an algorithm based on the expectation-maximization (EM). OCT1 C181T genotyping showed 100% homozygous wild-type (C/C). OCT1 C1022T genotyping showed wild-type (C/C), heterozygous (C/T) and homozygous mutant-type (T/T) and each accounted for 72.1, 24.5 and 3.4%, respectively. OCT2 G808T genotyping results also showed homozygous wild-type (G/G), heterozygous (G/T) and homozygous mutant-type (T/T) and each took 81.8, 17.9 and 0.3%, respectively. Based on these genotype data, haplotype analysis between OCT1 C181T and OCT1 C1022T has proceeded. The result has revealed that linkage disequilibrium between alleles is not obvious (P=0.0122).

Splenic infarcts are comparatively less common lesions. Caused by the occlusion of the major splenic artery or any of its branches, they are almost always due to emboli that arise in the heart. The spleen, along with the kidneys and brain, ranks as one of the most frequent sites of localization of systemic emboli. Infarcts may be small or large, multiple or single, and sometimes involve the entire organ. Usually these infarcts are of the bland anemic type. Septic infarcts are found in vegetative endocarditis of the valves of the left side of the heart. Much less often, infarcts in the spleen are caused by local thromboses, especially in leukemia, myeloproliferative syndrome, sickle cell anemia, polyarteritis nodosa, Hodgkin's disease, and bacteremic diseases. We experienced a rather unusual splenic infarction due to lymphoma in a 80-year-old man.

We investigated the sintering and consolidation phenomena of silver nanoparticles under various thermal treatment conditions when they were patterned by a contact printing technique on polyimide substrate films. The sintering of metastable silver nanoparticles commenced at 180 °C, where the point necks were formed at the contact points of the nanoparticles to reduce the overall surface area and the overall surface energy. As the temperature was increased up to 250 °C, silver atoms diffused from the grain boundaries at the intersections and continued to deposit on the interior surface of the pores, thereby filling up the remaining space. When the consolidation temperature exceeded 270 °C, the capillary force between the spherical silver particles and polyimide flat surface induced the permanent deformation of the polyimide films, leaving crater-shaped indentation marks. The bonding force between the patterned silver metal and polyimide substrate was greatly increased by the heat treatment temperature and the mechanical interlocking by the metal particle indentation.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and one of the commonly prescribed antidepressants. Numerous clinical observations and animal studies indicate that fluoxetine enhances the anticonvulsant potencies of several antiepileptic drugs. In the previous report, we showed that fluoxetine strongly protects against delayed cerebral ischemic injury. In the present study, the authors investigated whether fluoxetine has a beneficial effect on KA-induced neuronal cell death. An intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 microg) of KA produced typical neuronal cell death both in CA1 and CA3 regions of the hippocampus. Although, there was no significant difference in the time course or severity of epileptic behavior, the systemic administration of fluoxetine 30 min before KA administration significantly attenuated this neuronal cell death. Fluoxetine was found to suppress neuronal cell loss when injected at 10 mg/kg and the effect was enhanced at 50 mg/kg. Furthermore, this fluoxetine-induced neuroprotection was accompanied by marked improvements in memory impairment, as determined by passive avoidance tests. KA-induced gliosis and proinflammatory marker (COX-2, IL-1beta, and TNF-alpha) inductions were also suppressed by fluoxetine administration. It is interesting to note here that fluoxetine treatment suppressed NF-kappaB activity dose-dependently in KA-treated mouse brains, suggesting that this explains in part its anti-inflammatory effect. Together, these results suggest that fluoxetine has therapeutic potential in terms of suppressing KA-induced pathogenesis in the brain, and that these neuroprotective effects are associated with its anti-inflammatory effects.

Fluoxetine is a selective serotonin reuptake inhibitor that is widely used in the treatment of major depression including after stroke. In this study, we tested whether fluoxetine protects neuronal death in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO). The administration of fluoxetine intravenously (10 mg/kg) at 30 min, 3 hr, or 6 hr after MCAO reduced infarct volumes to 21.2+/-6.7%, 14.5+/-3.0%, and 22.8+/-2.9%, respectively, of that of the untreated control. Moreover, the neuroprotective effect of fluoxetine was evident when it was administered as late as 9 hr after MCAO/reperfusion. These neuroprotective effects were accompanied by improvement of motor impairment and neurological deficits. The fluoxetine-treated brain was found to show marked repressions of microglia activation, neutrophil infiltration, and proinflammatory marker expressions. Moreover, fluoxetine suppressed NF-kappaB activity dose-dependently in the postischemic brain and also in lipopolysaccharide-treated primary microglia and neutrophil cultures, suggesting that NF-kappaB activity inhibition explains in part its anti-inflammatory effect. These results demonstrate that curative treatment of fluoxetine affords strong protection against delayed cerebral ischemic injury, and that these neuroprotective effects might be associated with its anti-inflammatory effects.

Caffeic acid is a naturally occurring phenolic compound that is found in many fruits, vegetables, and herbs (e.g. sage), including coffee. Caffeic acid and its analogues have attracted much attention and have been studied in recent years because of their antiviral, anti-inflammatory, and neuroprotective properties, and their antioxidant effects. In particular, their antioxidative effects can be used for either the prevention of oxidative rancidity in foods or the treatment of diseases related to reactive oxygen species, such as stroke and Alzheimer’s diseases. However, since caffeic acid is not approved for direct use in food, due to it being a suspected human carcinogen based on testing in mice, there is still a need to develop an analogue that has similar biological properties. Bioisosterism is considered to be a powerful method for selecting molecular groups for drug design and lead compound development. By the application of bioisosterism, we previously found that replacing the catechol moiety in dopamine with 1-hydroxy-2-pyridone analogues resulted in similar dopaminergic activity. Based on those results, we replaced the functional catechol moiety in caffeic acid with 1-hydroxy-2-pyridone systems whose isosteric and isoelectric character are considered to be equivalent. Therefore, they are interchangeable in terms of their contributions to biological activity. In this article, we describe the syntheses of two 1-hydroxy-2-pyridone analogues (compounds 1 and 2) of caffeic acid and the evaluation of their antioxidant activities by an in vitro 1,1diphenyl-2-picryl-hydrazyl free radical (DPPH·) scavenging assay. The synthesis of the 5-substituted 1-hydroxy-2-pyridone analogue (1) is illustrated in Scheme 1. The Horner-Wadsworth-Emmons reaction of 6-methoxynicotin aldehyde using triethyl phosphonoacetate, lithium hydroxide (LiOH), and 4 A molecular sieves in tetrahydrofuran (THF) at room temperature gave ethyl 3-(6-methoxypyridin-3-yl)acrylate (3) in 82% yield. N-Oxidation of compound 3 with mchloroperbenzoic acid (m-CPBA) gave the N-oxide compound 4 in 68% yield. Removal of the methyl group with acetyl chloride under reflux conditions, followed by hydrolysis with an acetone-water mixture gave compound 5. Finally, base-catalyzed hydrolysis of the ester group in 5 gave the desired 5-substituted 1-hydroxy-2-pyridone analogue (1). As shown in Scheme 2, the synthesis of the 4-substituted 1-hydroxy-2-pyridone analogue (2) is started from methyl 2chloroisonicotinate, due to the commercial unavailability of 2-methoxynicotinaldehyde (8). For the synthesis of 8, methyl 2-chloroisonicotinate was first reacted with sodium methoxide in 1,4-dioxane to give a mixture of compound 6 and 2-chloroisonicotinic acid. The mixture resulted because de-esterification also occurred in the presence of the sodium methoxide. Reduction of the ester compound 6 with sodium borohydride and calcium chloride in THF gave compound 7, which was then partially oxidized with chromium (VI) oxide in dichloromethane to give compound 8. From the aldehyde compound 8, the target compound 2 was synthesized by the same reactions as those described for the synthesis of compound 1 from 6-methoxynicotinaldehyde (depicted in Scheme 1). The antioxidant activities of the synthesized 1-hydroxy-2pyridone analogues and caffeic acid were measured using the previously reported DPPH method, and the results are shown in Table 1. Although caffeic acid showed potent radical scavenging activity, the 1-hydroxy-2-pyridone analogues did not show any activity. These results clearly indicate that the antioxidant activity of caffeic acid is mainly attributed to the catechol moiety. In conclusion, two 1-hydroxy-2-pyridone analogues of Figure 1. Structure of caffeic acid.

Famciclovir, 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine, is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, Famvir tablet 750 mg (Novartis Korea Ltd.) and Famcivir tablet 750 mg (Hanmi Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, years in age and in body weight, were divided into two groups and a randomized cross-over study was employed. After a single tablet containing 750 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations ere similar at water. The pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed , and untransformed . The results showed that the differences between two formulations based on the reference drug, tablet 750 mg, were -0.53%, 1.12% and -24.82% for , and , respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., and for and , respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir tablet 750 mg was bioequivalent to Famvir tablet 750 mg.

A novel memory-based motion simulation (MBMS) model was developed as a general framework for simulating natural human motions for computer-aided ergonomic design. The MBMS model utilizes real human motion samples recorded in motion capture experiments as templates for simulating novel motions. Such human motion samples are stored in a motion database. When a user submits an input simulation scenario to the model, a motion search engine termed the ldquoroot motion finderrdquo in the model searches the motion database and retrieves the motion samples that closely match the given scenario. The retrieved motions, referred to as root motions, may significantly differ from one another in the underlying movement technique. Such variability within the root motion set is analyzed and graphically summarized by a model component termed the motion variability analyzer. This analysis helps users rapidly identify alternative movement techniques for the given input simulation scenario and simulate human motions based on alternative movement techniques. Since root motions do not exactly satisfy but only closely match the input simulation scenario, a motion modification (MoM) algorithm adapts them to fit the scenario by systematically deforming them in the joint angle-time domain. The MoM algorithm retains the root motions' fundamental spatial-temporal structure and minimizes deviations from the root motions during such deformations. The MBMS model overcomes limitations of existing simulation models and achieves the following: 1) simulation of categorically different motions based on a single unified model; 2) simple and efficient learning of new motion behaviors; and 3) representation and simulation of human motion variability.

A good yield of 5‐(N‐phenethylamino)salicylic acid derivatives was successfully obtained from the corresponding methyl 2‐acetoxy‐5‐(N‐phenethylamino)benzoate esters by rapid and selective reduction of the amide group in the acyl protected salicylic acid with NaBH4/acetic acid in dioxane followed by hydrolysis of the ester group.