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Background: Total knee arthroplasty (TKA) mainly involves the femoral, tibial, and bearing implants. Bearings are categorized by posterior cruciate ligament (PCL) status (cruciate-retaining [CR] vs. posterior-stabilized [PS]) and motion (mobile vs. fixed). This study assessed the impact of three bearing combinations (CR Mobile, PS Mobile, and PS Fixed) on one-year patient-reported outcome measures (PROMs) following TKA., Methods: In this retrospective analysis of 486 TKAs using the same prosthesis with varied bearings, patients were grouped as CR Mobile, PS Mobile, and PS Fixed. Patient characteristics, preoperative, and one-year postoperative PROMs (Forgotten Joint Scores [FJS] and Knee Society Scores [KSS], and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), were collected. Multivariate analysis was conducted to assess the impact of bearing type on one-year PROMs., Results: The multivariate regression model showed that bearing type significantly impacted the one-year FJS, with CR Mobile showing higher scores than PS Mobile and PS Fixed bearings (p < 0.001). However, bearing type did not significantly influence one-year KSS and WOMAC scores (all p > 0.05)., Conclusion: This study was the first to analyze the impact of the combination of PCL status and bearing motion in TKA. Bearing type selection had an impact on the one-year postoperative FJS, particularly favoring CR Mobile bearings. Other PROMs were not affected by the choice of bearing type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monoamniotic twins have a high risk of mortality and perinatal morbidity due to cord entanglement and vascular anastomosis. Despite efforts to reduce the mortality rate through intensive fetal surveillance and timed delivery, poor long-term neurodevelopmental outcomes remain an unsolved problem. This study aimed to identify novel biomarkers predicting abnormal neurodevelopmental outcomes in monoamniotic twins with cord blood samples taken at the time of delivery. Abnormal neurodevelopmental outcomes were defined as (1) a severe brain lesion on neonatal brain ultrasound, (2) developmental delay, (3) cerebral palsy, and/or (4) blindness or deafness. Cord blood was analyzed with mass spectrometry-based proteomics according to the neurodevelopmental outcomes. Statistical analysis was performed to determine the differentially expressed proteins between neonates with normal and abnormal neurodevelopmental outcomes. Several candidate proteins were further validated with enzyme-linked immunosorbent assays. A total of 20 neonates (10 pairs) of monoamniotic twins were included in the proteomic analysis, of which 25% had abnormal neurodevelopmental outcomes. Eighteen proteins were differentially expressed in neonates with abnormal neurodevelopmental outcomes. The upregulated proteins in the neonates with adverse neurodevelopmental outcome were immunoglobulin (Ig)-gamma-4 chain C region, apolipoprotein E, and alpha-fetoprotein. In contrast, Ig-lambda chain V region 4A, Ig-heavy variable 3, Ig-kappa chain C region, Ig-mu chain C region, C1q, ceruloplasmin, and Ig-lambda chain V-I region were decreased. In the validation experiment, the cord blood concentration of ceruloplasmin was significantly lower in neonates with adverse neurodevelopmental outcomes than in those without. Therefore, ceruloplasmin could be a useful predictive biomarker of adverse neurodevelopmental outcomes in monoamniotic twins., (© 2022. Society for Reproductive Investigation.)

Objective: To evaluate the association of sexual knowledge with sexual desire, sexual activity, and sexual satisfaction in hematopoietic stem cell transplantation (HSCT) patients and partners, and their willingness to participate in sexual education., Methods: This is a multi-center survey. Patients were eligible if they had received HSCT. Patients' current sexual partners were invited to the study unless they had limitations on sexual activity. Sexual desire, activity and satisfaction was assessed using the Sexual Activity Questionnaire. Sexual knowledge, experience of information seeking, sexual counseling or education, and willingness of participate in sexual education were assessed using questionnaire., Results: Of 151 participants, 61.8 % had experience of receiving counseling about their sexual issues after HSCT. Compared to the lower sexual knowledge group, participants with higher sexual knowledge reported to be 1.91 times more sexually active with 3.04 times higher sexual desire. Among the participants, 79.4 % of participants had the willingness to receive sexual education after HSCT and preferred to receive sexual education from sexual education specialists CONCLUSIONS: Higher sexual knowledge was associated with higher sexual desire, sexual activity, and sexual satisfaction., Practice Implications: Sexual education should be provided to patients and their partners after HCST by trained experts for HSCT patient's sexual life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In capacitive deionization, the salt-adsorption capacity of the electrode is critical for the efficient softening of brackish water. To improve the water-deionization capacity, the carbon electrode surface is modified with ion-exchange resins. Herein, we introduce the encapsulation of zwitterionic polymers over activated carbon to provide a resistant barrier that stabilizes the structure of electrode during electrochemical performance and enhances the capacitive deionization efficiency. Compared to conventional activated carbon, the surface-modified activated carbon exhibits significantly enhanced capacitive deionization, with a salt adsorption capacity of ∼2.0 × 10 -4 mg/mL and a minimum conductivity of ∼43 μS/cm in the alkali-metal ions solution. Encapsulating the activated-carbon surface increased the number of ions adsorption sites and the surface area of the electrode, which improved the charge separation and deionization efficiency. In addition, the coating layer suppresses side reactions between the electrode and electrolyte, thus providing a stable cyclability. Our experimental findings suggest that the well-distributed coating layer leads to a synergistic effect on the enhanced electrochemical performance. In addition, density functional theory calculation reveals that a favorable binding affinity exists between the alkali-metal ion and zwitterionic polymer, which supports the preferable salt ions adsorption on the coating layer. The results provide useful information for designing more efficient capacitive-deionization electrodes that require high electrochemical stability.

For efficient solar cells based on organic semiconductors, a good mixture of photoactive materials in the bulk heterojunction on the length scale of several tens of nanometers is an important requirement to prevent exciton recombination. Herein, we demonstrate that nanoporous titanium dioxide inverse opal structures fabricated using a self-assembled monolayer method and with enhanced infiltration of electron-donating polymers is an efficient electron-extracting layer, which enhances the photovoltaic performance. A calcination process generates an inverse opal structure of titanium dioxide (<70 nm of pore diameters) providing three-dimensional (3D) electron transport pathways. Hole-transporting polymers was successfully infiltrated into the pores of the surface-modified titanium dioxide under vacuum conditions at 200 °C. The resulting geometry expands the interfacial area between hole- and electron-transport materials, increasing the thickness of the active layer. The controlled polymer-coating process over titanium dioxide materials enhanced photocurrent of the solar cell device. Density functional theory calculations show improved interfacial adhesion between the self-assembled monolayer-modified surface and polymer molecules, supporting the experimental result of enhanced polymer infiltration into the voids. These results suggest that the 3D inverse opal structure of the surface-modified titanium dioxide can serve as a favorable electron-extracting layer in further enhancing optoelectronic performance based on organic or organic-inorganic hybrid solar cell.

High-quality large-sized hexagoal WSe2 crystals can be grown on dielectric substrates using atmospheric chemical vapor deposition in the presence of hydrogen gas. These hexagonal crystals (lateral width >160 um) have a carrier mobility of 100 cm(2) V(-1) s(-1) and a photoresponsivity of ≈1100 mA W(-1), which is comparable to that of exfoliated flakes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Zacco platypus, pale chub, is an indigenous freshwater fish of East Asia including Korea and has many useful characteristics as indicator species for water pollution. While utility of Z. platypus as an experimental species has been recognized, genetic-level information is very limited and warrants extensive research. Metallothionein (MT) is widely used and well-known biomarker for heavy metal exposure in many experimental species. In the present study, we cloned MT in Z. platypus and evaluated its utility as a biomarker for metal exposure. For this purpose, we sequenced complete complementary DNA (cDNA) of MT in Z. platypus and carried out phylogenetic analysis with its sequences. The transcription-level responses of MT gene following the exposure to CdCl2 were also assessed to validate the utility of this gene as an exposure biomarker. Analysis of cDNA sequence of MT gene demonstrated high conformity with those of other fish. MT messenger RNA (mRNA) expression and enzymatic MT content significantly increased following CdCl2 exposure in a concentration-dependent manner. The level of CdCl2 that resulted in significant MT changes in Z. platypus was within the range that was reported from other fish. The MT gene of Z. platypus sequenced in the present study can be used as a useful biomarker for heavy metal exposure in the aquatic environment of Korea and other countries where this freshwater fish species represents the ecosystem.

This study aimed to assess differences in genes related to skin color of goldfish (Carassius auratus) exposed to light-emitting diodes (LEDs): red, green, and purple. We investigated differences in the expression of mammalian-like melanopsin (Opn4m), rhodopsin (RH), melanin-concentrating hormone (MCH), melanin-concentrating hormone receptor (MCH-R), and proopiomelanocortin (POMC) in goldfish exposed to different LED light spectra. Opn4m, RH, MCH, and MCH-R mRNA levels were significantly higher in the green and purple LED groups than in the white fluorescent bulb (control) and red LED groups. Furthermore, skin cells were isolated to measure the MCH-R mRNA expression levels. The results show that the mRNA expression levels were significantly higher in the green and purple LED groups than in the control and red LED groups. In addition, body weights in the green and purple LED groups were significantly higher than those in the control and red LED groups. However, POMC mRNA expression levels in the green and purple LED groups were significantly lower than those in the control and red LED groups. These results suggest that specific wavelengths regulate fish skin color through neuropeptide hormones and photoreceptors, and POMC, which is related to stress hormones and melatonin, is associated with stress levels as well as skin color.

Leptin plays an important role in energy homeostasis and reproductive function in fish, especially in reproduction. Migrating fish, such as salmonoids, are affected by external environmental factors, and salinity changes are a particularly important influence on spawning migrations. The aim of this study was to test whether changes in salinity affect the expression of leptin, estrogen receptors (ERs), and vitellogenin (VTG) in chum salmon (Oncorhynchus keta). The expression and activity of leptin, the expression of ERs and VTG, and the levels of estradiol-17β and cortisol increased after the fish were transferred to FW, demonstrating that changes in salinity stimulate the HPG axis in migrating female chum salmon. These findings reveal details about the role of elevated leptin levels and sex steroid hormones in stimulating sexual maturation and reproduction in response to salinity changes in chum salmon.

Kisspeptins (Kiss) have been recognized as potent regulators of reproduction in teleosts, and Kiss is suggested to be a key regulator of the hypothalamus-pituitary-gonad axis (HPG). However, its regulatory role on reproduction in fish remains unclear. Therefore, to investigate the role of Kiss on fish reproduction, this study aimed to test differences in the hormones of the HPG axis, Kiss as neuropeptides, and sex steroids on the sexual maturation of paired cinnamon clownfish, Amphiprion melanopus, following treatment with Kiss. We investigated the actions of sex maturation hormones, including HPG axis hormones and sex steroid hormones, such as gonadotropin-releasing hormones, gonadotropin hormones (GTHs), GTH receptors, estrogen receptors, and vitellogenin in the pituitary, gonads, and liver following treatment with Kiss. The expression levels of HPG axis genes increased after the Kiss injection. In addition, the levels of plasma 17α-hydroxypregnenolone, estradiol-17β, and 11-ketotestosterone increased. These results support the hypothesis that Kiss play important roles in the regulation of the HPG axis and are most likely involved in gonadal development and sexual maturation in cinnamon clownfish., (Copyright © 2013 Elsevier Inc. All rights reserved.)

While there have been a number of studies on the effects of photoperiod and duration of light and dark exposure, much less information is available on the importance of light intensity. This study investigated the effects of exposure of goldfish, Carassius auratus exposed to white fluorescent bulbs, and red (peak at 630nm), and green (530nm) light emitting diodes (LEDs) at approximately 0.9W/m(2) (12-h light:12-h dark) for four months on a number of hormones of the hypothalamus-pituitary-gonad (HPG) axis, in vivo and in vitro. We investigated the effects of native GnRH molecules (gonadotropin-releasing hormones; salmon GnRH, sGnRH; and chicken GnRH-II, cGnRH-II), gonadotropin hormones (GTHα; follicle-stimulating hormone, FSH-β; luteinizing hormone, LH-β2), kisspeptin 1 (Kiss1) and G protein-coupled receptor 54 (GPR54) mRNA levels. Furthermore, we measured LH and 17α-hydroxypregnenolone levels in plasma and we performed gonad histological observations. GnRHs, Kiss1, GPR54 and GTH mRNA and plasma LH and 17α-hydroxypregnenolone levels in the in vivo and in vitro groups exposed to green LEDs were significantly higher than the other groups. Histological analysis revealed the presence of oocytes in the yolk stage in fish exposed to green light. These results suggest that green wavelengths regulate the HPG axis and enhance sexual maturation in goldfish., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study investigated the effects of exposure to different light spectra and intensities on ovarian maturation in yellowtail damselfish, Chrysiptera parasema over a 4-months period. We used a white fluorescent bulb and three different light-emitting diodes (LEDs: red, peak at 630nm; green, 530nm; blue, 450nm), at three different intensities each (0.3, 0.6, and 0.9W/m(2)). The effects of different illuminations were assessed by measuring the mRNA and protein expressions of vitellogenin (VTG) and estrogen receptor (ER), gonadosomatic index (GSI), and plasma estradiol-17β (E2) hormone level. For green and blue lights, significantly higher levels of VTG and ER expressions, GSI, and plasma E2 were obtained, compared to the other light spectra. Histological analysis revealed the presence of vitellogenic oocytes in fish exposed to short wavelengths (green and blue) light. In addition, we observed significantly greater ovarian maturation in fish exposed to low and medium light intensities. The results indicate that exposure to green low intensity lighting accelerates gonadal maturation, and is likely to facilitate development of more energy-efficient aquaculture procedures., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study aimed to examine the role of 2 aquaporin (AQP) isoforms (AQP3, and -8) in sockeye salmon (Oncorhynchus nerka) in response to a hyperosmotic challenge from freshwater to seawater (SW) during the parr and smoltification (smolt) stages. AQP3 mRNA was primarily detected in the osmoregulatory organs, such as gills, while AQP8 mRNA was primarily found in the intestine. These results suggested that AQP isoforms play a role in osmoregulation in specific osmoregulatory organs. Similarly, AQP3 mRNA expression in the gills (mean values:1.06 ± 0.05 [parr] and 1.29 ± 0.07 [smolt]) was significantly higher than AQP8 mRNA levels (parr: 0.04 ± 0.003; smolt: 0.14 ± 0.004), and in the intestine, AQP8 mRNA expression (parr: 0.89 ± 0.007; smolt: 1.91 ± 0.03) was significantly higher than AQP3 mRNA levels (parr: 0.24 ± 0.006; smolt: 0.83 ± 0.005); these expression patterns were similar in vivo and in vitro. Additionally, AQP mRNA levels were lower in cortisol treated than in control groups. Therefore, these results suggest that AQPs play important roles in the water absorption mechanisms associated with multiple AQP isoforms, and that cortisol enhances the hypo-osmoregulatory capacity of fish in SW, and also controls the expression of AQPs in a hyperosmotic environment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Clopidogrel selectively inhibits platelet aggregation. Clopidogrel bisulfate (Plavix(®)) was first developed for atherothrombosis prevention and is commonly prescribed for this indication. A new clopidogrel formulation, clopidogrel besylate (KOVIX(®)), has recently been developed., Objective: This study was designed to compare the multiple-dose pharmacokinetics/pharmacodynamics and tolerability of clopidogrel besylate with those of clopidogrel bisulfate in 40 healthy male subjects., Methods: This was an open-label, randomized-sequence, multiple-dose, two-period, two-treatment crossover study. The subjects were randomly assigned to a sequence group that received two treatments: clopidogrel besylate 75 mg followed by clopidogrel bisulfate 75 mg, or vice versa. The subjects received a 300-mg loading dose on day 1 followed by 75 mg daily for the next 4 days. Serial blood samples were collected to determine the concentrations of clopidogrel and its carboxylic acid metabolite, SR26334. Platelet aggregation and bleeding times were measured. Tolerability was evaluated throughout the study., Results: The clopidogrel plasma concentration-time profiles of the formulations were similar. The measured pharmacokinetic parameters did not differ significantly between the clopidogrel besylate and clopidogrel bisulfate groups. The geometric mean ratios of the clopidogrel besylate group to the clopidogrel bisulfate group with respect to the maximum plasma concentration (C(max)) and the area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUC(last)) were 0.96 (90 % confidence interval [CI] 0.82, 1.12) and 0.95 (0.81, 1.11), respectively. Moreover, the pharmacokinetic parameters of SR26334 did not differ significantly between the two treatment groups. Furthermore, the areas under the platelet aggregation inhibition-time curves (AUIC) and the maximum inhibitory effects (I(max)) did not differ significantly between the two groups. The geometric mean ratios (clopidogrel besylate to clopidogrel bisulfate) were 1.01 (90 % CI 0.95, 1.08) for the I(max) and 0.98 (0.89, 1.07) for the AUIC. Both formulations were well tolerated and exhibited comparable safety profiles., Conclusion: This study demonstrated that the pharmacokinetic/pharmacodynamic profiles of clopidogrel besylate were not significantly different from those of clopidogrel bisulfate. Both formulations were well tolerated in healthy subjects.

The present study aimed to test starvation-induced oxidative stress in the cinnamon clownfish Amphiprion melanopus illuminated by light-emitting diodes (LEDs): red (peak at 630 nm), green (peak at 530 nm), and blue (peak at 450 nm) within a visible light. We investigated the oxidative stress induced by starvation for 12 days during illumination with 3 LED light spectra through measuring antioxidant enzyme (superoxide dismutase [SOD] and catalase [CAT]) mRNA expression and activity; CAT western blotting; and measuring lipid peroxidation [LPO]), plasma H(2)O(2), lysozyme, glucose, alanine aminotransferase (AlaAT), aspartate aminotransferase (AspAT), and melatonin levels. In green and blue lights, expression and activity of antioxidant enzyme mRNA were significantly lower than those of other light spectra, results that are in agreement with CAT protein expression level by western blot analysis. Also, in green and blue lights, plasma H(2)O(2), lysozyme, glucose, AlaAT, AspAT, and melatonin levels were significantly lower than those in other light spectra. These results indicate that green and blue LEDs inhibit oxidative stress and enhance immune function in starved cinnamon clownfish., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Pharmacokinetic (PK) profiles of glimepiride and metformin have been established for the combination drug as well as each agent individually. However, the PK profiles of a combination drug containing glimepiride and sustained-release (SR) metformin have not been reported. To compare the pharmacokinetic profiles of glimepiride/SR metformin (2 mg/500 mg) with the PK of immediate-release (IR) formulations, an open-label, randomized, 3-period, 3-sequence, 3-treatment, crossover study was conducted in 12 healthy subjects., Methods: After a single administration of glimepiride/SR metformin 2 mg/500 mg (Treatment) or glimepiride/metformin IR 2 mg/500 mg (Reference 1), or administration of 2 doses of glimepiride/metformin IR 1 mg/250 mg 12 h apart (Reference 2), serial blood samples were collected and drug concentrations determined by liquid chromatography/ tandem mass spectrometry. PK parameters (Cmax and AUC24) for glimepiride and metformin were log-transformed and compared using a mixed-effects model analysis of variance (ANOVA). The mean differences and 95% confidence intervals (CIs) were back-transformed to obtain geometric mean ratios along with the CIs for the ratios., Results: Treatment demonstrated similar systemic exposures for glimepiride; the geometric mean ratio (95% CIs) for glimepiride AUC24 was 1.05 (0.97 - 1.13) for Treatment relative to Reference 1 and 1.08 (1.00 - 1.17) for Treatment relative to Reference 2. The SR formulation showed a delay in the time to reach maximum concentration for metformin from 1.0 - 4.0 h to 4.0 - 8.0 h and a decreased AUC24 value; the geometric mean ratio for metformin AUC24 was 0.87 (0.74 - 1.03) for Treatment relative to Reference 1 and 0.75 (0.63 - 0.88) for Treatment relative to Reference 2., Conclusions: This study demonstrates for the first time that fixed-dose glimepiride and SR metformin 2 mg/500 mg shows a PK profile similar to that of glimepiride, but with a delayed time to maximum concentration and slightly decreased bioavailability for metformin compared with the IR fixed-dose combination, in healthy volunteers. PK profiles from this exploratory study will be helpful in designing and conducting further studies in diabetic patients.

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in the control of reproduction and gonadal maturation in teleost fish. Fish have multiple GnRH genes that encode structurally distinct peptides. We identified salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH-II (cGnRH-II) by cDNA cloning in cinnamon clownfish (Amphiprion melanopus) using reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends-PCR (RACE-PCR). Gene identity was confirmed by sequence alignment and subsequent phylogenetic analyses. We also investigated GnRH mRNA expression in the gonads by quantitative real time-PCR (Q-PCR), and measured plasma estradiol-17β (E(2)) levels in immature fish following treatment with the three molecular forms of GnRHs. The expression levels of sGnRH, sbGnRH, and cGnRH-II mRNA were higher in mature testes and ovaries, as compared to the levels in gonads at earlier stages of maturity. The levels of the three prepro-GnRH mRNA species and the plasma E(2) levels increased after injection of the three GnRH variants. These findings support the hypothesis that GnRH peptides play important roles in the regulation of the hypothalamic-pituitary-gonadal axis and are probably involved in paracrine control of gonadal development and sex change in cinnamon clownfish., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Lobeglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist with partial PPAR-α affinity, was developed to treat type 2 diabetes mellitus., Objective: This study's aim was to evaluate the tolerability and pharmacokinetic (PK) properties of lobeglitazone to satisfy regulatory requirements for marketing approval in Korea., Methods: A block-randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy subjects. In the pilot study, 4 subjects were administered 0.5 mg, including 1 receiving a placebo. Then, the single-dose study was conducted with 1, 2, 4, and 8 mg doses (8 subjects in each group, including 2 receiving placebos), followed by the multiple-dose study with 1, 2, and 4 mg doses (once daily for 7 days; 8 subjects in each group, including 2 receiving placebos). Serial samples of blood and urine were collected and drug concentrations were determined by high turbulence liquid chromatography-LC/MS/MS. Tolerability assessments were performed throughout the study. Adverse events (AEs) were determined from general health-related questions and self-reports., Results: Thirty-six (mean [SD]; age, 23.6 [2.7] years; weight, 70.0 [6.9] kg) and 25 Korean male subjects (age, 23.5 [3.1] years; weight 69.4 [9.4] kg) were enrolled in the single- and multiple-dose studies, respectively. The data from subjects administered lobeglitazone who completed the study (27, single; 18, multiple) was included in the PK analyses. In the single-dose study, the AUC and C(max) of lobeglitazone increased with the dose. After repeated dosing for 7 days, the accumulation ratio ranged from 1.1 to 1.4. A total of 25 AEs were reported by 11 (30.6%) and 8 subjects (33.3%) in the single- and multiple-dose studies, respectively. All AEs were mild in intensity and not serious., Conclusions: Lobeglitazone was well tolerated in this small, selected group of healthy male Korean volunteers. The AUC and C(max) of lobeglitazone increased in a dose-proportional manner from 1 to 4 mg., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

The present study aimed to test the effects of melatonin on oxidative stress in the yellowtail clownfish, Amphiprion clarkii, as produced by light emitting diodes (LEDs): red, green, and blue. We investigated the effects of the different LEDs on oxidative stress by measuring the mRNA expression of arylalkylamine N-acetyltransferase (AANAT2), the expression and activities of antioxidant enzymes (superoxide dismutase, SOD (EC 1.15.1.1); and catalase, CAT (EC 1.11.1.6)), and plasma H2O2 and plasma melatonin levels. In red light, the expression of AANAT2, SOD, and CAT mRNA was significantly higher than those under the other light spectra. SOD and CAT activities and plasma H2O2 and melatonin levels were also significantly higher for the red spectra than those for the other light spectra. These results indicate that red light induces oxidative stress. To investigate the effects of melatonin on oxidative stress, we injected melatonin into live fish (in vivo) or treated cultured pineal organ (in vitro) with melatonin. We found that AANAT2, SOD, and CAT mRNA expression levels, SOD and CAT activities, and plasma H2O2, lipid peroxidation (LPO) and melatonin levels were significantly lower than those for the controls. Therefore, our results indicate that red light induces oxidative stress and melatonin plays the role of a strong antioxidant in yellowtail clownfish.

Background: A fixed-dose combination tablet of tramadol/acetaminophen exhibits both rapid and sustained analgesic effects due to different pharmacologic activities. To prolong analgesia and improve patient convenience, an extended-release (ER) tablet of this agent has been developed., Objective: The aim of this study was to explore the pharmacokinetic profiles of the new ER tramadol/acetaminophen fixed-dose combination and compare them with those of a conventional immediate-release (IR) formulation after multiple dosing as a Phase I clinical exploratory trial., Methods: An open-label, randomized, 2-sequence crossover study was conducted in healthy volunteers. All subjects received both formulations for 4 days: either 1 IR tablet (tramadol 37.5 mg/acetaminophen 325 mg) q6h followed by 1 ER tablet (tramadol 75 mg/acetaminophen 650 mg) q12h, or vice versa. A 5-day washout period separated the 2 treatments. Tramadol and acetaminophen concentrations in plasma were determined simultaneously using LC-MS/MS, and the pharmacokinetic properties were analyzed by noncompartmental method. To compare the systemic exposure of the 2 formulations, the geometric mean ratios (GMRs) for AUC(0-12,ss) and the 90% CIs were calculated. Adverse events (AEs) were identified through subject interviews, recording of vital signs, physical examinations, 12-lead electrocardiography, and clinical laboratory assessments., Results: Twelve healthy, nonsmoking, Korean male subjects completed the study. The mean (SD) age was 24.4 (5.2) years and the mean body weight was 65.1 (6.0) kg. The T(max,ss) for tramadol was delayed until 3 hours after the ER treatment, compared with 1 hour after the IR treatment, whereas the T(max,ss) of acetaminophen was 30 minutes after each treatment. The mean (SD) of AUC(0-12,ss) in the IR and ER formulations was 2789.0 (507.7) and 2638.7 (469.1) µg/h/L for tramadol and 42,635.0 (8711.2) and 40,394.3 (10,127.7) µg/h/L for acetaminophen, respectively. The GMR of ER to IR for AUC(0-12,ss) was 0.95 (90% CI, 0.91-0.99) for tramadol and 0.94 (90% CI, 0.89-0.99) for acetaminophen. A total of 17 AEs occurred in 9 subjects; all AEs were considered mild or moderate and resolved without medical intervention. The most frequent AEs were headache and dizziness (3 cases each)., Conclusions: The ER formulation displayed a similar AUC(0-12,ss) to that of the IR formulation for tramadol and acetaminophen., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Objective: This study compared the bioavailability and tolerability of a fixed-dose combination (FDC) tablet of glimepiride/metformin 2/500 mg and glimepiride 2-mg + metformin 500-mg tablets administered separately in healthy Korean subjects., Methods: In this single-dose, open-label, 2-period crossover study, healthy Korean volunteers were randomly assigned to receive, in 1 of 2 randomized sequences, an FDC tablet of glimepiride/metformin 2/500 mg (test) and glimepiride 2-mg + metformin 500-mg tablets administered separately (reference), with a 1-week washout period between treatments. Plasma concentrations of glimepiride and metformin were measured using LC/MS-MS. Pharmacokinetic parameters were analyzed using noncompartmental methods. Bioequivalence was concluded if the 90% CIs of the geometric mean test/reference ratios (GMRs) of the logarithm-transformed C(max), AUC from 0 to 30 hours (AUC(0-30)), and AUC(0-infinity) values were within the predetermined regulatory range of 80% to 125%. Tolerability was assessed using physical examination and laboratory analysis., Results: A total of 32 subjects were enrolled (16 men [mean (SD) age, 21.8 (2.7) years (range, 18-26 years); weight, 68.9 (8.3) kg (range, 55.5-85.0 kg)]; 16 women [age, 23.5 (4.5) years (range, 20-38 years); weight, 51.7 (3.5) kg (range, 46.8-58.0 kg)]). The GMRs (90% CI) of glimepiride C(max), AUC(0-30), and AUC(0-infinity) were 1.01 (0.91-1.11), 0.98 (0.92-1.03), and 0.97 (0.93-1.04), respectively. For metformin, these values were 0.96 (0.87-1.06), 0.96 (0.90-1.03), and 0.96 (0.90-1.03). A total of 49 adverse events (AEs) were reported in 10 subjects (31.3%) with the FDC and in 13 subjects (40.6%) with the separate tablets. The most commonly reported AEs with the test and reference treatments were dizziness (6 [19%] and 7 [22%]) and sweating (4 [13%] and 7 [22%]), respectively. The severity of all of the AEs was considered to be mild, and there were no significant differences in the prevalences of AEs between the 2 formulations., Conclusions: In this study in healthy Korean subjects, the requirements for bioequivalence of the glimepiride/metformin 2/500-mg FDC and coadministration of separate tablets of each drug were met. Both formulations were generally well tolerated., (2010 Excerpta Medica Inc. All rights reserved.)

We determined oxidative stress by measuring the expression and activity of 3 antioxidant enzymes [Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase (CAT) and glutathione peroxidase (GPX)] in black porgy exposed to thermal (20 degrees C-->30 degrees C) and hypoosmotic (35 psu-->10 psu and 0 psu) stresses. The expression and activity of antioxidant enzymes were significantly higher after exposure to 30 degrees C, 10 psu, and 0psu. Furthermore, we measured H(2)O(2) and lipid peroxidation (LPO) levels. As a result, H(2)O(2) and LPO levels were significantly increased after exposure to thermal (20 degrees C-->30 degrees C) and hypoosmotic stress (35 psu-->10 psu and 0 psu) stress. These results indicate that thermal and hypoosmotic stress induces oxidative stress in black porgy. Additionally, we investigated the changes due to thermal and hypoosmotic stress by measuring plasma cortisol and ion (Na(+) and Cl(-)) levels. Plasma cortisol levels increased at 30 degrees C and at 10 psu and then decreased at 0 psu. However, plasma Na(+) and Cl(-) levels did not change after exposure to thermal stress (30 degrees C), and decreased at 10 psu and 0 psu. In conclusion, thermal and hypoosmotic environments increase oxidative stress, thereby these results may be indicators of oxidative stress in black porgy., (Copyright 2010 Elsevier Inc. All rights reserved.)

The role of NKT cells in the pathogenesis of collagen-induced arthritis (CIA) remains unclear since most studies have used C57BL/6 (B6) mice, which are less susceptible to CIA than mice with a DBA/1 background. To clarify the immunological functions of NKT cells in CIA, it is necessary to analyze in detail the effects of NKT cell deficiency on CIA development in DBA/1 mice. The incidence and severity of CIA were significantly exacerbated in DBA/1CD1d(+/-) mice as compared to DBA/1CD1d(-/-) mice. In DBA/1CD1d(+/-) mice, antigen-specific responses of B and T cells against CII were remarkably increased and inflammatory cytokine levels were also increased in vivo and in vitro. The number of IL-17-producing NKT cells significantly increased in DBA/1CD1d(+/-) mice as the disease progressed. Our results clearly show that NKT cells are involved not only in accelerating the severity and incidence of CIA but also in perpetuating the disease progression.

Background: Ticlopidine is an antiplatelet agent used for the prevention of vascular accidents. In clinical practice in Korea, ginkgo extract may be administered along with ticlopidine to enhance the inhibition of platelet aggregation., Objective: To meet the requirements for marketing a combined fixed-dose formulation in Korea, the investigators compared the pharmacokinetic characteristics of ticlopidine in a combined fixed-dose tablet of ticlopidine/ginkgo extract with the concomitant administration of ticlopidine and ginkgo extract tablets., Methods: An open-label, 2-period, 2-treatment, single-dose, randomized-sequence crossover study was conducted in healthy Korean male volunteers. Subjects were randomly allocated to 2 sequence groups. In one period, a combined ticlopidine 250 mg/ ginkgo extract 80-mg fixed-dose tablet was administered and, in the other period, ticlopidine 250-mg and ginkgo extract 80-mg tablets were concomitantly administered. A 7-day washout separated the 2 periods. For analysis of pharmacokinetic properties, including C(max), T(max), t((1/2)), AUC(0-infinity), and AUC(0-last), serial blood sampling was performed up to 48 hours after study drug administration during each period. Ticlopidine concentrations in plasma were determined by a validated method using LC-MS/MS. In order for the 2 treatments to be considered bioequivalent, the 90% CI of the geometric means ratios for C(max) and AUC needed to be between 80% and 125%. Bleeding time was determined before dosing (0 hour) and at 5 and 24 hours after dosing. Adverse events (AEs) were identified through patient interview, recording of blood pressure, heart rate, and body temperature, physical examination, 12-lead ECG, and laboratory assessments., Results: Twenty-four healthy Korean male subjects (mean [range] age, 23.9 [22-38] years; height, 174.0 [162-184] cm; weight, 67.4 [56-80] kg) completed the study. Median (range) T(max) of ticlopidine was 1.5 (0.5-2.0) hours in both groups. The mean (SD) t((1/2)) of ticlopidine in the combined fixed-dose formulation and the concomitant administration groups was 19.5 (3.4) and 19.0 (3.3) hours after study drug administration, respectively. The geometric means ratios of ticlopidine AUC(0-last), AUC(0-infinity), and C(max) between the combined fixed-dose formulation and concomitant administration were 1.04 (90% CI, 0.96-1.13), 1.04 (90% CI, 0.96-1.13), and 1.09 (90% CI, 0.96-1.23), respectively. The mean (SD) bleeding time at predose (0), and 5 and 24 hours after dose administration was 4.5 (1.6) to 5.4 (1.7) minutes in the combined fixed-dose formulation group and 4.4 (1.6) to 5.1 (1.1) minutes in the concomitant administration group. Five subjects (3 in the combined fixed-dose formulation group and 2 in the concomitant administration group) had bleeding times >8 minutes, but this was not considered to be clinically significant. A total of 24 AEs were reported in 13 of 24 subjects: nausea (3 cases), diarrhea (3), dizziness (3), epigastric discomfort (2), headache (2), rhinorrhea (2), purulent sputum (2), dyspepsia (1), upper abdominal pain (1), cough (1), pharyngolaryngeal pain (1), oropharyngeal swelling (1), dysphonia (1), and dysphagia (1). All were considered mild or moderate in nature. There was no statistically significant difference between the 2 treatments in the number of AEs or in the number of subjects who reported an AE., Conclusion: Administration of a single dose of a combined fixed-dose formulation of ticlopidine 250 mg/ ginkgo extract 80-mg tablets and concomitant administration of ticlopidine and ginkgo extract tablets did not result in statistically significant differences in the pharmacokinetics of ticlopidine in these healthy Korean male volunteers.

We cloned full-length sox3 cDNA from testis of black porgy, Acanthopagrus schlegeli. Black porgy sox3 cDNA consists of 897 base pairs (bp) and encodes a protein of 298 amino acids. We have investigated the expression pattern of sox3 and DMRT1 mRNA during the sex-reverse process from male to female (immature testis, mature testis, testicular portion of mostly testis, ovarian portion of mostly testis, testicular portion of mostly ovary, ovarian portion of mostly ovary and ovary). The expression of sox3 and DMRT1 mRNA was high in mature testis of black porgy during sex-reverse process. In a histological analysis, testicular portion of gonad was degenerated and the ovary portion was increased during sex reversal from male to female, and then oocytes were increased in ovary. Also we examined the expression of sox3 and DMRT1 mRNA after gonadotropin-releasing hormone analogue (GnRHa) treatment in immature black porgy. The expression of sox3 and DMRT1 mRNA was increased after GnRHa treatment (in vivo and in vitro experiment) in immature black porgy. Therefore, we concluded that sox3 and DMRT1 were involved in the development of testis than ovary in black porgy.

Background: LC15-0444 is a selective inhibitor of dipeptidyl peptidase (DPP) IV under investigation in Korea for the treatment of type 2 diabetes., Objective: The aim of this study was to investigate the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of a single dose of LC15-0444 in healthy male subjects., Methods: A dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study was performed in healthy Korean male subjects assigned to receive 25, 50, 100, 200, 400, or 600 mg of LC15-0444 capsules. Blood and urine samples were collected up to 72 hours after administration. Plasma and urine drug concentrations were determined by tandem mass spectrometry coupled with high-performance liquid chromatography. DPP IV activity was measured by continuous spectrophotometric assay. An additional food effect study was performed in the 100-mg dose group; changes in PK and PD parameters after high-fat diet were evaluated. Adverse events (AEs) were detected through investigator inquiries, spontaneous reports, and clinical evaluations such as physical examinations, vital sign measurements, 12-lead electrocardiography, clinical laboratory tests (eg, hematology, blood chemistry, coagulation, urinalysis), and computerized impedance cardiography., Results: Sixty Korean men (mean age, 25.3 years [range, 19-39 years]; weight, 68.3 kg [range, 53.6-84.9 kg]) were enrolled, providing 10 subjects for each dose group. After administration, LC15-0444 reached T(max) at 0.5 to 5.1 hours, and was eliminated with a t((1/2)) of 16.7 to 21.3 hours. The mean fraction of unchanged drug excreted in urine ranged from 0.21 to 0.34 and mean renal clearance was 15.5 to 23.6 L/h. The dose-normalized AUC exhibited dose-linearity over the range of 50 to 400 mg. All doses of LC15-0444 =200 mg were found to inhibit 80% of DPP IV activity for 24 hours. High-fat diet did not significantly influence the AUC of LC15-0444. LC15-0444 was generally well tolerated. None of the subjects developed any serious clinical or laboratory AEs or discontinued the study due to an AE. All AEs were mild or moderate, and no dose-related trends were observed. Forty-six AEs were reported in 18 subjects (30.0%). AEs considered to be related to the study drug were headache (6 cases), dizziness (2), nausea (1), epistaxis (1), and increased heart rate (1). All AEs resolved spontaneously., Conclusions: A single dose of LC15-0444 exhibited linear PK properties over the range of 50 to 400 mg in these healthy Korean male subjects. PK characteristics were not significantly influenced by food. In addition, doses >or=200 mg of LC15-0444 inhibited plasma DPP IV activity by >80% over a 24-hour dosing interval, and a 600-mg dose increased active glucagon-like peptide-1 levels after a standardized meal. LC15-0444 was generally well tolerated.

Estrogens play an important role in many physiological processes in both female and male vertebrates, mediated by specific nuclear receptor, estrogen receptors (ERs). We have isolated a third ER (ERbeta2), which was found to contain 2004 nucleotides including an open reading frame that encodes 667 amino acids. We have also cloned ERalpha and ERbeta1 from the published information (GenBank accession nos. AY074780 and AY074779) and investigated the expression pattern of these ER subtypes in the gonads during gonad sex change of black porgy by quantitative polymerase chain reaction. Maturity stages can be divided into five stages during the sex change process from immature male to female (immature male, mature male, male of mostly testis, male of mostly ovary and mature female). The expression of ERalpha mRNA was highest in the ovary of mature female, followed by the testis of mature male and testicular portion of mostly testis. ERbeta1 expression was higher in the mature testis and ovary than in the gonads of other maturity stages. In contrast to that, ERbeta2 was highest in the ovary of mature female, and significantly lower levels of ERbeta2 expression were observed in the gonads of the other maturity stages. The present study describes the molecular characterization of ERbeta2, and documents the expression changes of three ER subtypes during sex change process of the protandrous black porgy.

We cloned complementary DNA (cDNA) encoding metallothionein (MT) and superoxide dismutase (SOD) from the liver of olive flounder, Paralichthys olivaceus. The full-length MT cDNA consists of 183 base pairs (bp) and encodes a protein of 60 amino acids; partial SOD cDNA consists of 326 bp and encodes a protein of 109 amino acids. We investigated the dose- and time-related effects of the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) on MT and SOD mRNA using quantitative polymerase chain reaction (QPCR). The expression levels of MT mRNA were highest at 24 h (about five times) in 10 microg/L BaP, and at 6 h (about twelve times) in 30 microg/L BaP. The expression levels of SOD mRNA were highest at 12 h (about three times) in 10 microg/L BaP, and at 6 h (about six times) in 30 microg/L BaP, and then decreased toward the end of the experiment. We also measured plasma glucose and cortisol, all of which increased with BaP exposure. These results suggest that MT and SOD play an important role in the detoxification of reactive oxygen species (ROS) caused by BaP exposure, and thus may be indicators of oxidative stress responses.