Assessment of Safety, Effects, and Muscle-Specific Accumulation of Dietary Butylated Hydroxytoluene (BHT) in Paralichthys olivaceus.

Butylated hydroxytoluene (BHT) is a commonly used antioxidant added to animal/fish feed to limit lipid autoxidation and peroxidation. Although there have been reviews and reports of BHT toxicity in animals, limited information is available with respect to the toxic effects and accumulation of BHT due to oral exposure in aquaculture species. Therefore, 120 days of feeding trial was conducted to evaluate the effects of dietary BHT on the marine fish olive flounder Paralichthys olivaceus. Graded levels of BHT were added to the basal diet in increments of 0, 10, 20, 40, 80, and 160 mg BHT/kg, corresponding to 0 (BHT0), 11 (BHT11), 19 (BHT19), 35 (BHT35), 85 (BHT85), and 121 (BHT121) mg BHT/kg diets, respectively. Fish with an average weight of 77.5 ± 0.3 g (mean ± SD) were fed one of the six experimental diets in triplicate groups. Growth performance, feed utilization, and survival rate were not significantly affected by the dietary BHT levels among all experimental groups, whereas BHT concentration in the muscle tissue was found to increase in a dose-dependent manner up to 60 days of the experimental period. Thereafter, BHT accumulation in muscle tissue showed a declining trend among all treatment groups. Furthermore, the whole-body proximate composition, nonspecific immune responses, and hematological parameters (except triglycerides) were not significantly influenced by the dietary levels of BHT. Blood triglyceride content was significantly higher in fish fed the BHT-free diet compared to all other treatment groups. Thus, this study demonstrates that dietary BHT (up to 121 mg/kg) is a safe and effective antioxidant without exhibiting any adverse effects on the growth performance, body composition, and immune responses in the marine fish olive flounder, P. olivaceus.

Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells.

Mouse embryonic stem cells (mESCs) exhibit self-renewal and pluripotency, can differentiate into all three germ layers, and serve as an essential model in stem cell research and for potential clinical application in regenerative medicine. Melanoma-associated antigen A2 (MAGEA2) is not expressed in normal somatic cells but rather in different types of cancer, especially in undifferentiated cells, such as in the testis, differentiating cells, and ESCs. However, the role of MAGEA2 in mESCs remains to be clarified. Accordingly, in this study, we examined the expression and functions of MAGEA2 in mESCs. MAGEA2 messenger RNA (mRNA) expression was decreased during mESCs differentiation. MAGEA2 function was then evaluated in knockdown mESC. MAGEA2 knockdown resulted in decreased pluripotency marker gene expression in mESCs consequent to increased Erk1/2 phosphorylation. Decreased MAGEA2 expression inhibited mESC proliferation via S phase cell cycle arrest with a subsequent decrease in cell cycle-associated genes Cdk1, Cdk2, Cyclin A1, Cyclin D1, and Cdc25a. Apoptotic mESCs markedly increased along with cleaved forms of caspases 3, 6, and 7 and PARP expression, confirming caspase-dependent apoptosis. MAGEA2 knockdown significantly decreased embryoid body size in vitro when cells were differentiated naturally and teratoma size in vivo, concomitant with decreased ectoderm marker gene expression. These findings suggested that MAGEA2 regulates ESC pluripotency, proliferation, cell cycle, apoptosis, and differentiation. The enhanced understanding of the regulatory mechanisms underlying diverse mESC characteristics will facilitate the clinical application of mESCs.

PRPF4 is a novel therapeutic target for the treatment of breast cancer by influencing growth, migration, invasion, and apoptosis of breast cancer cells via p38 MAPK signaling pathway.

Pre-mRNA processing factor 4 (PRPF4), a core protein in U4/U6 snRNP, maintains snRNP structures by interacting with PRPF3 and cyclophilin H. Expression of the PRPF4 gene affects cell survival as well as apoptosis and is responsible for retinitis pigmentosa (RP). Proteomics analysis shows that PRPF4 may be a therapeutic target in human cancers. Nevertheless, the exact function and role of the PRPF4 gene are unclear. In this study, we assessed the expression of PRPF4 gene in human breast cancer cells. First, we confirmed that the PRPF4 gene was overexpressed in various breast cancer cell lines. Next, using breast cancer cell lines MCF7 and MDA-MB-468, we established stable cell lines with PRPF4 gene knockdown. We also performed microarray analysis to investigate molecular mechanisms underlying PRPF4 activity. All cell lines with PRPF4 gene knockdown exhibited reduced cell proliferation, remarkable reduction in anchorage-independent colony formation capacity, and reduction of PCNA protein, which is a marker cell of proliferation. Reduced expression of the PRPF4 gene induced apoptosis and changes in the expression of associated apoptotic markers in breast cancer cell lines. Knockdown of the PRPF4 gene reduced cellular capacity for migration and invasion (the key hallmarks of human cancers) and decreased the expression of genes involved in epithelial-mesenchymal transition (EMT). Microarray results showed that the expression of PPIP5K1, PPIPK2, and YWHAE genes was reduced at the transcriptional level, leading to reduced phosphorylation of p38 MAPK. These findings suggest that knockdown of PRPF4 gene slows down breast cancer progression via suppression of p38 MAPK phosphorylation. In conclusion, the PRPF4 gene plays an important role in the growth of breast cancer cells and is therefore a potential therapeutic target.

Suppression of PRPF4 regulates pluripotency, proliferation, and differentiation in mouse embryonic stem cells.

Mouse embryonic stem cells (mESCs) are characterized by their self-renewal and pluripotency and are capable of differentiating into all three germ layers. For this reason, mESCs are considered a very important model for stem cell research and clinical applications in regenerative medicine. The pre-mRNA processing factor 4 (PRPF4) gene is known to have a major effect on pre-mRNA splicing and is also known to affect tissue differentiation during development. In this study, we investigated the effects of PRPF4 knockdown on mESCs. First, we allowed mESCs to differentiate naturally and observed a significant decrease in PRPF4 expression during the differentiation process. We then artificially induced the knockdown of PRPF4 in mESCs and observed the changes in the phenotype. When PRPF4 was knocked down, various genes involved in mESC pluripotency showed significantly decreased expression. In addition, mESC proliferation increased abnormally, accompanied by a significant increase in mESC colony size. The formation of mESC embryoid bodies and teratomas was delayed following PRPF4 knockdown. Based on these results, the reduced expression of PRPF4 affects mESC phenotypes and is a key factor in mESC. SIGNIFICANCE OF THE STUDY: Our results indicate that PRPF4 affects the properties of mESCs. Suppression of PRPF4 resulted in a decrease in pluripotency of mESC and promoted proliferation. In addition, suppression of PRPF4 also resulted in decreased apoptosis. Moreover, the inhibition of PRPF4 reduced the ability to differentiate and formation of teratoma in mESC. Our results demonstrated that PRPF4 is a key factor of controlling mESC abilities.

Clinical significance of serum apolipoproteins as a predictor of coronary heart disease risk in Korean men.

OBJECTIVE: Although serum apolipoprotein measurement is known to be associated with coronary heart disease (CHD) risk, there is only limited information about the clinical significance of lipid profiles such as ApoA, ApoB and A/B ratio in predicting CHD risk in Asians. Therefore, this cohort study was conducted to evaluate the longitudinal effects of baseline serum apolipoprotein measurements on CHD risk in Korean men. DESIGN: Initially, an intermediate and high Framingham risk score (FRS)-free cohort of 23 918 healthy Korean men was followed until 2010. FRS was calculated for each man and divided into three levels of risk <10% (low), 10-19% (intermediate) and ≥20% (high). More-than-a-moderate CHD risk group (participants with FRS ≥ 10%) and high CHD risk group (participants with FRS ≥ 20%) were defined as our two dependent variables. Cox proportional hazards models were performed. RESULTS: In the more-than-a-moderate CHD risk group, the total and average follow-up periods were 83340·2 and 3·48 person-years, respectively, and 3763 (15·7%) incident cases developed between 2006 and 2010. In the high CHD risk group, the total and average follow-up periods were 87868·8 and 3·67 person-years, respectively, and 344 (1·4%) incident cases developed between 2006 and 2010. Multivariate-adjusted analyses showed a strong statistically significant relationship between the quintile groups of apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1) and apolipoprotein B/apolipoprotein A-1 (ApoB/A-1) ratio and both the more-than-a-moderate CHD risk and high CHD risk. CONCLUSIONS: Serum ApoB, ApoA-1 and ApoB/A-1 ratio levels are independently associated with CHD risk in Korean men.

Sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous determination of benzyl butyl phthalate and its metabolites, monobenzyl phthalate and monobutyl phthalate, in rat plasma, urine, and various tissues collected from a toxicokinetic study.

This study describes the development of a sensitive liquid chromatography-electrospray-tandem mass spectrometry method for the simultaneous determination of benzyl butyl phthalate (BBP) and its major metabolites, monobenzyl phthalate (MBzP) and monobutyl phthalate (MBuP), in rat plasma, urine, and 10 different tissues. The method was validated with regard to the specificity, linearity, precision, accuracy, lower limit of quantification (LLOQ), recovery, and stability by using the matrix-matched quality control samples. The assay achieved LLOQ of 1 ng/ml of BBP for plasma and urine, 4 ng/g for kidney and liver, 10 ng/g for fat, and 20 ng/g for all other tissues. For MBzP and MBuP, the assay achieved LLOQ of 5 ng/ml for plasma and urine, 10 ng/g for fat, and 20 ng/g for all other tissues. The disposition of BBP was characterized by a large volume of distribution (71.1-82.9 l/kg) and a high clearance (838.7-871.0 ml/min/kg). It was extensively metabolized to MBzP and MBuP, with their levels consistently exceeding the BBP levels. The distribution of BBP, MBzP, and MBuP to tissues of kidney, liver, stomach, small intestine, large intestine, spleen, brain, testis, thyroid, and fat was determined under steady-state conditions. For BBP, the steady-state tissue-to-plasma partition coefficient (K p) was the highest for fat (25.0) followed by small intestine (2.6), thyroid (2.0), and stomach (1.1). In contrast, for MBzP and MBuP, it was the highest for kidney (2.0 and 4.3, respectively) and liver (4.3 and 2.1, respectively) but was less than unity for all other tissues. The developed assay method and findings of this study may be useful to evaluate the exposure and toxic potential of BBP and its metabolites in risk assessment.

Larvicidal activity of naturally occurring naphthalenedione and its structurally related analogs against three mosquito species.

The objective of this study was to determine the larvicidal activity of an active compound isolated from Cercis chinensis heartwood and its structurally related analogs against 4th-stage Aedes aegypti, Culex pipiens pallens, and Ae. togoi. The larvicidal compound of C. chinensis was isolated with the use of various chromatographic techniques and identified as analogs of 1,4-naphthalenedione. Based on the median lethal concentration (LC(50)) values of commercially procured analogs against Ae. aegypti larvae, the most toxic analog was 2-bromo-1,4-naphthalenedione (1.19 µg/ml); followed by 5-hydroxy-1,4-naphthalenedione (1.72 µg/ml); 2-methyl-1,4-naphthalenedione (9.12 µg/ml); 2-hydroxy-1,4-naphthalenedione (10.76 µg/ml); and 2-methoxy-1,4-naphthalenedione (12.50 µg/ml). Similar results were observed against Cx. p. pallens and Ae. togoi larvae with 1,4-naphthalenedione analogs. These results also showed that 1,4-naphthalenedione analogs were less toxic than the organophosphate pirimiphos-methyl. Nonetheless, naturally occurring C. chinensis-derived materials and 1,4-naphthalenedione analogs have potential for development as mosquito larvicidal agents.

Percutaneous absorption, disposition, and exposure assessment of homosalate, a UV filtering agent, in rats.

Homosalate (HMS) is an ultraviolet (UV) filtering agent used in sunscreens and other cosmetics for skin protection purposes. Despite the widespread use of these products, absorption, disposition, and in vivo endocrine disrupting potential of HMS have not been characterized. Thus, the aim of this study was to examine the percutaneous absorption, disposition, and exposure assessment of HMS in rats. Initially, sunscreen preparations of petrolatum jelly, oily solution, lotion, and gel were prepared and evaluated for in vitro permeation of HMS across excised rat skin. Dermal permeability was greatest for gel, and this preparation was used in subsequent in vivo topical application investigations. After iv injection (0.5, 2, or 5 mg/kg), the pharmacokinetics of HMS was linear and was characterized by a large Vd(ss) (13.2-17 L/kg), high Cl(s) (4.5-6.1 L/h/kg), and long t½ (6.1-8.4 h). After topical application of gel, the bioavailability of HMS was 5.4 ± 1.1 and 4.2 ± 0.6% for high and low doses (10 and 20 mg), respectively. Consistent with the prolonged absorption (Tmax 11.2 ± 1.8 and 12 ± 0 h for low and high doses, respectively), the terminal t½ was longer after topical application (23.6-26.1 h) compared to iv injection. A population pharmacokinetic model was further developed to simultaneously fit the time courses of plasma concentrations and dermal content data after iv injection and topical application. Findings of this study may be useful to further examine the relationship between exposure and endocrine disrupting potential of HMS in risk assessment.

Acaricidal activities against house dust mites of spearmint oil and its constituents.

The aim of this study was to evaluate the acaricidal activities of spearmint oil and carvone derivatives against house dust mites using contact and fumigant toxicity bioassays to replace benzyl benzoate as a synthetic acaricide. Based on the LD50 values, the contact toxicity bioassay revealed that dihydrocarvone (0.95 and 0.88 µg/cm2) was 7.7 and 6.8 times more toxic than benzyl benzoate (7.33 and 6.01 µg/cm2) against Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively, followed by carvone (3.78 and 3.23 µg/cm2), spearmint oil (5.16 and 4.64 µg/cm2), carveol (6.00 and 5.80 µg/cm2), and dihydrocarveol (8.23 and 7.10 µg/cm2). Results of the fumigant toxicity bioassay showed that dihydrocarvone (2.73 and 2.16 µg/cm2) was approximately 4.0 and 4.8 times more effective than benzyl benzoate (11.00 and 10.27 µg/cm2), followed by carvone (6.63 and 5.78 µg/cm2), carveol (7.58 and 7.24 µg/cm2), spearmint oil (9.55 and 8.10 µg/cm2), and dihydrocarveol (9.79 and 8.14 µg/cm2). Taken together, spearmint oil and carvone derivatives are a likely viable alternative to synthetic acaricides for managing house dust mites.

Acaricidal activities of bicyclic monoterpene ketones from Artemisia iwayomogi against Dermatophagoides spp.

The acaricidal properties of 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one isolated from Artemisia iwayomogi and its structural analogues were evaluated against Dermatophagoides farinae and D. pteronyssinus, and their effects were compared with that of the commercial acaricide benzyl benzoate. Based on the 50 % lethal dose (LD50) values against D. farinae, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (0.82 µg/cm(2)) was 9.71 times more effective than benzyl benzoate (7.96 µg/cm(2)), followed by (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (1.03 µg/cm(2)), (1S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (1.58 µg/cm(2)), and (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one oxime (3.05 µg/cm(2)) in a filter paper bioassay. The acaricidal activities of 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one and its structural analogues against D. pteronyssinus were similar to those against D. farinae. These results demonstrate that naturally occurring A. iwayomogi-isolated 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one and its structural analogues are suitable for the production of natural acaricides against house dust mites.

Antimicrobial potentials of active component isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues against foodborne bacteria.

BACKGROUND: Synthetic preservatives have been consistently used to maintain the quality of food products. However, the degree of danger to human health cannot be ignored. In this study, the antimicrobial activities of Citrullus colocynthis fruits and 4-methylquinoline analogues were investigated to develop natural preservatives against foodborne bacteria. RESULTS: Antimicrobial activities of the methanol extract and five fractions derived from C. colocynthis fruits were evaluated against five foodborne bacteria. The chloroform fraction possessed strong activities against five foodborne bacteria. 4-Methylquinoline was isolated by chromatographic analyses. To establish the structure-activity relationships, the antimicrobial activities of 4-methylquinoline analogues (2-hydroxyquinoline, 4-hydroxyquinoline, 6-hydroxyquinoline, 2-methylquinoline, 6-methyquinoline, 8-methylquinoline and 2-methyl-8-hydroxyquinoline) were tested against food-borne bacteria. When employing the agar diffusion method, 2-methyl-8-hydroxyquinoline was found to have potent activities against the five foodborne bacteria. In terms of minimum bactericidal concentration or minimum inhibitory concentration, 2-methyl-8-hydroxyquinoline had significantly higher antimicrobial activity against the five foodborne bacteria. CONCLUSION: Citrullus colocynthis fruits and 4-methylquinoline analogues could be useful for the development of eco-friendly food supplemental agents and pharmaceuticals.

Relationship between organophosphate and pyrethroid pesticides and metabolic syndrome in Korean farmers.

BACKGROUND: The global use of pesticides steadily increased until the early 2010s. Pesticides play a significant role in agriculture in Korea. Metabolic syndrome is more prevalent in rural areas than in urban areas. This study explored the potential association between organophosphate and pyrethroid pesticide exposure and metabolic syndrome. METHODS: This study enrolled 1,317 individuals who participated in the Pesticide Exposure and Intoxication Study conducted by the Dankook University Hospital Center for Farmers' Safety and Health from 2014 to 2019. Urinary levels of dimethylphosphate, dimethylthiophosphat, diethylphosphate, and diethylthiophosphate were measured to assess organophosphate pesticide exposure and urinary levels cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, and 3-phenoxybenzoic acid were measured to assess pyrethroid pesticide exposure. RESULTS: The odds ratio for the 4th quartile group of organophosphate metabolites concentration was 1.48 (95% confidence interval: 1.06-2.09) compared to the 1st quartile group after adjustment for general factors. In addition, a positive trend was observed across the quartile groups of organophosphate metabolites concentration. A positive trend was noted across the quartile groups of organophosphate metabolites in males, while no significant association was observed in females. Furthermore, no significant associations were observed between metabolic syndrome and pyrethroid metabolites concentration. CONCLUSIONS: A positive correlation was observed between the prevalence of metabolic syndrome and the concentrations of urinary organophosphate metabolites, consistent with previous research finding. This association may be attributed to the action of organophosphates as acetylcholinesterase inhibitors, stimulating beta cells in the islets of Langerhans. This can lead to alterations in lipid metabolism and insulin resistance, ultimately leading to metabolic syndrome development. Metabolic syndrome is a major contributor to cardiovascular disease; therefore, it is necessary to identify the risk factors unique to rural areas, such as pesticide exposure.

New computerized indices for quantitative evaluation of depression and asymmetry in patients with chest wall deformities.

An evaluation index that can quantitatively assess the severity of chest wall deformities is essential to prepare and assess corrective surgical operations for patients with these deformities, including funnel chest patients. In previous studies, our group proposed several automatically calculated indices that represent the severity of depression and asymmetry in the chest wall. These indices showed sufficient performance in most cases of deformities, including those involving asymmetric and symmetric depression; however, their linearity declined when assessing complex deformities. The purpose of this study is to propose two automated indices that provide linear evaluation output for all types of chest wall deformities, including complex deformities, and to evaluate their performance and clinical feasibility. Six reference chest wall boundary curves were obtained from 60 computed tomography (CT) images of a normal chest. Next, an active contour model-based image processing technique was used to extract boundary curves from images of patients with real chest wall deformities. Third, the required parameters were extracted from the boundary curves and the targeted indices were calculated. Finally, the performance of the proposed indices was evaluated using 33 synthetic images and 60 real chest CT images of patients with chest wall deformities. The newly proposed indices can be automatically calculated from the original CT images and showed sufficient performance for all types of chest wall deformities. We believe that the newly proposed indices can facilitate pre- and postoperative evaluation of chest wall deformities in clinical practice.

Acaricidal toxicities of 1-hydroxynaphthalene from Scutellaria barbata and its derivatives against house dust and storage mites.

The essential oil of Scutellaria barbata was extracted using a steam distillation and then evaluated via fumigant and contact toxicity bioassays against Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Tyrophagus putrescentiae. The acaricidal toxicities of 1-hydroxynaphthalene from S. barbata oil and its derivatives were determined and compared with those of benzyl benzoate. Based on the LD50 values of 1-hydroxynaphthalene derivatives against D. farinae, D. pteronyssinus, and T. putrescentiae, obtained using a fumigant toxicity bioassay, the acaricidal activity of 1-hydroxynaphthalene (2.11, 2.37, and 4.50 µg/cm2) was 4.76, 6.00, and 2.68 times higher than that of benzyl benzoate (10.05, 9.50, and 12.50 µg/cm2) in the corresponding order, which was followed by that of 2-hydroxynaphthalene (9.50, 9.00, and 11.50 µg/cm2). On the contact toxicity bioassay, the acaricidal activity of 1-hydroxynaphthalene (0.79, 0.92, and 2.50 µg/cm2) was 9.49, 6.52, and 3.76 times higher than that of benzyl benzoate (7.50, 6.00, and 9.41 µg/cm2), which was followed by that of 2-hydroxynaphthalene (4.21, 4.80, and 6.50 µg/cm2). In conclusion, our results indicate that S. barbata oil and 1-hydroxynaphthalene derivatives might be effective natural agents for the management of house dust and storage mites.

The association between uric acid and chronic kidney disease in Korean men: a 4-year follow-up study.

There have been many studies between serum uric acid (UA) and chronic kidney disease (CKD). However, as far as we know, little research has been done to examine the prospective association between serum UA and development of CKD in Korean men. This prospective cohort study was performed using 18,778 men who participated in a health checkup program both on January, 2005 and on December, 2009. CKD was defined as an estimated glomerular filtration rate < 60 mL/min per 1.73 m(2). The odds ratio (OR) from binary logistic regressions for the development of CKD was determined with respect to the quintiles grouping based on serum UA. During 74,821.4 person-years of follow-up, 110 men were found to develop CKD. The OR for the development of CKD increased as the quintiles for baseline serum UA levels increased from the first to fifth quintiles (1.00 vs 1.22, 1.19, 2.59, and 3.03, respectively, p for linear trend < 0.001) after adjusting for covariates. The adjusted OR comparing those participants with hyperuricemia ( ≥ 7.0 mg/dL) to those with normouricemia ( < 7.0 mg/dL) was 1.96 (1.28-2.99). Elevated serum UA levels were independently associated with increased likelihood for the development of CKD in Korean men (IRB number: KBC10034).

Reliability and Validity of Emotrics in the Assessment of Facial Palsy.

The globally accepted evaluation method for facial palsy is the House-Brackmann facial grading system; however, it does not reflect minute changes. Several methods have been attempted, but there is no universally accepted evaluation method that is non-time-consuming and quantitative. Recently, Emotrics, a two-dimensional analysis that incorporates machine-learning techniques, has been used in various clinical fields. However, its reliability and validity have not yet been determined. Therefore, this study aimed to examine and establish the reliability and validity of Emotrics. All patients had previously received speech therapy for facial palsy at our hospital between January and November 2022. In speech therapy at our hospital, Emotrics was routinely used to measure the state of the patient's facial palsy. A frame was created to standardize and overcome the limitation of the two-dimensional analysis. Interrater, intrarater, and intrasubject reliability were evaluated with intraclass correlation coefficients (ICC) by measuring the indicators that reflect eye and mouth functions. Validity was evaluated using Spearman's correlation for each Emotrics parameter and the House-Brackmann facial grading system. A total of 23 patients were included in this study. For all parameters, there was significant interrater and intrarater reliability (ICC, 0.61 to 0.99). Intrasubject reliability showed significant reliability in most parameters (ICC, 0.68 to 0.88). Validity showed a significant correlation in two parameters (p-value < 0.001). This single-center study suggests that Emotrics could be a quantitative and efficient facial-palsy evaluation method with good reliability. Therefore, Emotrics is expected to play a key role in assessing facial palsy and in monitoring treatment effects more accurately and precisely.

Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry.

This study describes the development of a rapid and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) assay for the quantification of [6]-gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 → 177.1 for [6]-gingerol and 294.2 → 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10-10,000 ng/mL (r ≥ 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 µL). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]-gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]-gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration-time curve (AUC(inf)) with no significant change in the systemic clearance (Cl(s)), volume of distribution (V(ss)) and elimination half-life (t(1/2)) as a function of dose.

In vitro and in vivo metabolism of verproside in rats.

Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to verproside glucuronides (M1 and M2), verproside sulfates (M3 and M4), picroside II (M5), M5 glucuronide (M7), M5 sulfate (M9), isovanilloylcatalpol (M6), M6 glucuronide (M8), M6 sulfate (M10), 3,4-dihydroxybenzoic acid (M11), M11 glucuronide (M12), M11 sulfates (M13 and M14), 3-methyoxy-4-hydroxybenzoic acid (M15), M15 glucuronides (M17 and M18), M15 sulfate (M20), 3-hydroxy-4-methoxybenzoic acid (M16), M16 glucuronide (M19), and M16 sulfate (M21). Incubation of verproside with rat hepatocytes resulted in thirteen metabolites (M1-M11, M13, and M14). Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of verproside, the drug was recovered in bile (0.77% of dose) and urine (4.48% of dose), and O-methylation of verproside to picroside II (M5) and isovanilloylcatalpol (M6) followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of verproside in rats.

The relevant factors of work-related fatigue for occupational vibration-exposed employees.

Background: To date, little is known about the effects of factors linked to work-related fatigue on vibration-exposed workers. Thus, the purpose of this study was (1) to assess the effects of vibration exposure time per week and work-related fatigue on workers and (2) to identify factors associated with work-related fatigue caused by long-term exposure to occupational vibration. Methods: This study used data collected from the 5th Korean Working Conditions Survey. A total of 34,820 non-vibration-exposed and 10,776 vibration-exposed employees were selected from the data. The χ2 and multiple logistic regression were used to determine the effect of vibration exposure time per week and the effects of factors of work-related fatigue on workers. Results: The prevalence of work-related fatigue in vibration-exposed workers (30.5%) was higher than that of non-exposed workers (15.9%). The prevalence of work-related fatigue was higher for female and workers with depression, anxiety, and shift work, and those with authority to control their work pace had statistically significantly higher odds than those who did not. The employees who had the authority to control their order of work (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.81-0.95) and method of work (OR: 0.90; 95% CI: 0.82-0.98) had statistically significantly lower odds than those who did not. The OR of work-related fatigue symptoms was highest among employees whose vibration exposure time per week were 30.0%-40.0% (OR: 2.36; 95% CI: 1.96-2.83). Lower OR was observed as vibration exposure time per week decreased. Conclusions: The results of the present study suggest an association between occupational vibration and work-related fatigue and longer vibration exposure time per week, causing an increased prevalence of work-related fatigue symptoms. Measures to protect workers exposed to occupational vibration from work-related fatigue must be taken.

The relationship between serum ferritin and metabolic syndrome in healthy Korean men.

BACKGROUND AND OBJECTIVE: Elevated serum ferritin levels have been reported to be associated with several metabolic disorders. We investigated the relationship between serum ferritin level and metabolic syndrome and its components in healthy Korean men. METHODS: In this cross-sectional study, serum ferritin level and metabolic syndrome and its components were measured from 18 581 men from January to December in 2008. The presence of metabolic syndrome was determined according to the most recent consensus report of the National Cholesterol Education Program's Third Adult Treatment Panel. Logistic regression models were applied to examine the relationship between the serum ferritin level and the metabolic syndrome and its components. RESULTS: After adjusting for clinical covariates, the odds ratio and 95% confidence intervals of metabolic syndrome with respect to Q2, Q3 and Q4 were 1.34 (1.14-1.57), 1.49 (1.24-1.70) and 1.99 (1.70-2.33), respectively (p for trend < 0.001). The multivariable-adjusted model also showed a significantly graded relationship between individual components of metabolic syndrome and the quartile groups of serum ferritin. CONCLUSIONS: In this study, elevated ferritin concentration is independently associated with metabolic syndrome and its components among healthy Korean men.