Associations of chronotype and insomnia with menstrual problems in newly employed nurses at university hospitals in the Republic of Korea.

Background: Dysmenorrhea and menstrual cycle changes occur in women working shifts. Circadian rhythm disruption and sleep disturbances associated with shift work leads to health problems. We identified chronotypes and the occurrence of insomnia among newly employed university hospital nurses and investigated the association of these factors with menstrual problems. Methods: We conducted pre-placement health examinations for shift workers using self-reported questionnaires between 2018 and 2020. A total of 463 nurses were included in the study. Sociodemographic data, shift work experience, and information on insomnia were collected from health examination data. In addition, details regarding chronotype, dysmenorrhea, irregular and abnormal menstrual cycles, amenorrhea, and contraceptive use were obtained from the questionnaire. Multiple logistic regression analysis was performed to study the association between chronotype, insomnia, and menstrual problems after controlling for age, body mass index, contraceptive use, amenorrhea, and prior shift work. Results: The prevalence rates of dysmenorrhea, irregular menstrual cycles, and longer menstrual cycles were 23.8%, 14.9%, and 4.1%, respectively. The risk of dysmenorrhea increased in the evening-type (odds ratio [OR]: 3.209; 95% confidence interval [CI]: 1.685-6.113) and those with insomnia (OR: 1.871; 95% CI: 1.074-3.261). Additionally, the risk of an irregular menstrual cycle (OR: 2.698; 95% CI: 1.167-6.237) increased in the evening-type, and the risk of a longer menstrual cycle (OR: 4.008; 95% CI: 1.354-11.864) increased in individuals with insomnia. Conclusions: Our findings suggest that dysmenorrhea is promoted in the evening-type and insomnia individuals. There may be an increased risk of irregular menstrual cycles among evening-type nurses and an increased risk of longer menstrual cycles among those with insomnia. Therefore, factors such as evening-type and insomnia should be considered for the prevention of menstrual problems in women performing shift work.

Health inequalities of 57,541 prisoners in Korea: a comparison with the general population.

OBJECTIVES: This study aimed to examine health disparities between prisoners and the general population in Korea. METHODS: We sought to estimate the prevalence of 17 physical and mental diseases using the nationwide medication prescription dataset among the total population of prisoners (n=57,541) in Korea. Age- and sex- standardized prevalence ratios (SPRs) were estimated to compare the disease prevalence between the prisoners and the general population. The disease prevalence for the general population was calculated from the prescription dataset for a representative of the Korean population (n=926,246) from the 2013 Korean National Health Insurance Service-National Sample Cohort. Furthermore, the prevalence of these diseases was compared between prisoners and a low-income segment of the general population (n=159,781). RESULTS: Compared to the general population, prisoners had higher prevalence of almost all physical and mental diseases, including hyperlipidemia (SPR, 20.18; 95% confidence interval [CI], 19.43 to 20.94), pulmonary tuberculosis (SPR, 9.58; 95% CI, 7.91 to 11.50), diabetes (SPR, 6.13; 95% CI, 5.96 to 6.31), cancer (SPR, 2.36; 95% CI, 2.07 to 2.68), and depression (SPR, 46.73; 95% CI, 44.14 to 49.43). When compared with the low-income population segment, higher prevalence were still found among prisoners for most diseases, including pulmonary tuberculosis (SPR, 6.39; 95% CI, 5.27 to 7.67) and depression (SPR, 34.71; 95% CI, 32.79 to 36.72). CONCLUSIONS: We found that prisoners were more likely to be unhealthy than the general population, even in comparison with a low-income segment of the general population in Korea.

Rejection of workers' compensation claims may increase depressive symptoms among firefighters with occupational injury: a nationwide study in South Korea.

OBJECTIVES: This study sought to examine whether the experience of occupational injuries was associated with depressive symptoms and whether the rejection of workers' compensation claims was associated with depressive symptoms among Korean firefighters. METHODS: We conducted a nationwide survey of 6793 Korean firefighters in 2015. Based on the experience of occupational injuries and workers' compensation claims over the past year, respondents were classified into four groups: "Not injured", "Injured, not applied", "Injured, applied, but rejected" and "Injured, applied, and accepted." Depressive symptoms over the preceding week were assessed using the 11-item version of the Centers for Epidemiologic Studies Depression Scale. RESULTS: Compared to firefighters who did not get injured, injured firefighters had a higher prevalence of depressive symptoms (PR 2.01, 95% CI 1.83, 2.22) after controlling for confounders including job assignment. Also, when we restricted the analysis to injured firefighters, a higher prevalence of depressive symptoms was observed among "Injured, applied, but rejected" (PR 1.70, 95% CI 1.11, 2.59) group, compared to "Injured, applied, and accepted" group. CONCLUSIONS: This finding suggests that rejection of workers' compensation claims, as well as the experience of occupational injuries, may increase the risk of depressive symptoms among Korean firefighters.

Relationship Between Shift Intensity and Insomnia Among Hospital Nurses in Korea: A Cross-sectional Study.

OBJECTIVES: This study explored the relationship between shift intensity and insomnia among hospital nurses. METHODS: The participants were 386 female hospital nurses who underwent a special health examination for night workers in 2015. The Korean Insomnia Severity Index (ISI), indices of shift work intensity, and other covariates such as amount of exercise, level of alcohol consumption, employment duration, and hours worked were extracted from the health examination data. The indices for shift intensity were (1) number of 3 consecutive night shifts and (2) number of short recovery periods after a previous shift, both assessed over the prior 3 months. Multiple logistic regression analysis adjusted for the aforementioned covariates was performed to evaluate the association of shift intensity with insomnia, defined as an ISI score of ≥8. RESULTS: The nurses with insomnia tended to be younger (p=0.029), to have worked 3 consecutive night shifts more frequently (p<0.001), to have experienced a greater number of short recovery periods after the previous shift (p=0.021), and to have worked for more hours (p=0.006) than the nurses without insomnia. Among the other variables, no statistically significant differences between groups were observed. Experiences of 3 or more consecutive night shifts (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.29 to 4.20) and 3 or more short recovery periods (OR, 2.01; 95% CI, 1.08 to 3.73) were associated with increased odds of insomnia. CONCLUSIONS: The results suggest that decreasing the shift intensity may reduce insomnia among hospital nurses working rotating shifts.

Loss of permanent employment and its association with suicidal ideation: a cohort study in South Korea.

Objective Precarious employment is associated with worse mental health, but it is unclear whether changes in employment status are related to suicidal behaviors. This study examined the association between change in employment status and suicidal ideation among workers in South Korea. Methods To maximize power of the analysis, we combined data from the ongoing Korean Welfare Panel Study. We analyzed 3793 participants who were permanent workers at baseline (2011-2014) and who either: (i) maintained permanent employment; (ii) became a full-time precarious worker; (iii) became a part-time precarious worker; or (iv) became unemployed in the following year (2012-2015). Suicidal ideation was assessed annually by asking participants, "Have you ever seriously thought about dying by suicide in the past year?" Logistic regression was applied to examine associations between change in employment status and suicidal ideation, adjusting for potential confounders such as lifetime suicidal ideation and depressive symptoms at baseline. Results Participants who became part-time precarious workers were more likely to have suicidal ideation [odd ratio (OR) 2.37, 95% confidence interval (95% CI) 1.07-5.25, P=0.033] compared to those who remained permanent workers. In analysis restricted to workers who never previously thought about dying by suicide, suicidal ideation was more common among those who became either full-time (OR 2.33, 95% CI 1.09-4.99, P=0.029) or part-time (OR 3.94, 95% CI 1.46-10.64, P=0.007) precarious workers. Conclusions Our findings suggest that change in employment status from permanent to precarious employment may increase suicidal ideation among workers in South Korea.

Effects of HM30181, a P-glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of loperamide in healthy volunteers.

AIMS: HM30181 is a third generation P-glycoprotein (P-gp) inhibitor currently under development. The objectives of this study were to evaluate the effects of a single dose of HM30181 on the pharmacodynamics and pharmacokinetics of loperamide, a P-gp substrate, and to compare them with those of quinidine. METHODS: Eighteen healthy male subjects were administered loperamide alone (period 1) or with loperamide plus quinidine or HM30181 in period 2 or 3, respectively. In period 3, subjects randomly received one of three HM30181 doses: 15, 60 or 180 mg. Changes in pupil size, alertness, oxygen saturation and the oral bioavailability of loperamide were assessed in each period. In addition, the pharmacokinetics of HM30181 were determined. RESULTS: Pupil size, alertness and oxygen saturation did not change over time when loperamide alone or loperamide plus HM30181 was administered while HM30181 significantly increased the systemic exposure to loperamide, i.e. the geometric mean ratio (90% confidence interval) of AUC(0,tlast ) for loperamide with and without HM30181 was 1.48 (1.08, 2.02). Co-administered quinidine significantly increased the systemic exposure to loperamide 2.2-fold (1.53, 3.18), which also markedly reduced pupil size, resulting in a decrease of 24.7 mm h in the area under the effect curve of pupil size change from baseline compared with loperamide alone. CONCLUSIONS: HM30181 inhibits P-gp mainly in the intestinal endothelium, which can be beneficial because pan-inhibition of P-gp, particularly in the brain, could lead to detrimental adverse events. Further studies are warranted to investigate adequately the dose-exposure relationship of HM30181, along with its duration of effect.

Pharmacokinetic and pharmacodynamic properties of a new long-acting granulocyte colony-stimulating factor (HM10460A) in healthy volunteers.

BACKGROUND: HM10460A is a newly developed recombinant human granulocyte colony-stimulating factor with long-lasting characteristics. This factor is expected to be used for chemotherapy-related neutropenic conditions. OBJECTIVE: The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of HM10460A following subcutaneous administration to healthy Korean subjects. METHODS: A randomized, double-blind, placebo-controlled, escalating single-dose study was conducted in 40 healthy Korean subjects. The subjects were allocated to single-dose groups of 5, 15, 45, 135 or 350 µg/kg, or placebo. Serial blood samples for pharmacokinetic/pharmacodynamic analyses were collected up to 22 days, and urine samples for pharmacokinetic analysis were collected up to 3 days after subcutaneous administration of HM10460A. The serum and urine concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: Most of the serum concentrations in the 5 and 15 µg/kg dosing groups were below the lower limit of quantification (LLOQ). The median times to the peak concentration (T(max)) of HM10460A in the 45, 135, and 350 µg/kg dosing groups were 8.0, 14.0, and 24.0 h, respectively. The mean ± standard deviation values of the dose-normalized maximum concentration (C(max)) and dose-normalized area under the concentration-time curve (AUC(last)) for the 45, 135, and 350 µg/kg dosing groups were 14.13 ± 6.37, 66.19 ± 38.71, and 34.65 ± 19.69 µg/L/mg, respectively, and 265.0 ± 124.1, 2144 ± 1232, and 1386 ± 701.2 µg h/L/mg, respectively. The concentrations of HM10460A in the urine were below the LLOQ in all of the subjects. In all of the dosing groups, the area under the effect-time curve (AUEC(last)) of both the absolute neutrophil count (ANC) and the CD34(+) cell count increased as the dose increased. CONCLUSION: HM10460A showed dose-dependent pharmacokinetic characteristics, and the systemic exposure of HM10460A was positively correlated with the ANC and CD34(+) cell counts.

Evaluation of the pharmacokinetics, food effect, pharmacodynamics, and tolerability of DA-1229, a dipeptidyl peptidase IV inhibitor, in healthy volunteers: first-in-human study.

BACKGROUND: Inhibitors of dipeptidyl peptidase (DPP) IV are a class of oral hypoglycemic agents that increase glucagon-like peptide-1 (GLP-1) levels by inhibiting its degradation. OBJECTIVE: This study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of DA-1229, which is a newly developed DPP IV inhibitor. This study was planned as part of a product development project at the request of the Korean regulatory agency. METHODS: A 7 parallel arm dose-escalation study was conducted in healthy Korean male volunteers. A single oral dose of DA-1229 or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 1.25, 2.5, 5, 10, 20, 40, or 60 mg. To assess the effects of food, the subjects in the 10-mg dose group received a single dose of DA-1229 10 mg after a high-fat meal, crossing over from the administration of DA-1229 under a fasting state, after a 7-day washout period. Serial blood samples were collected up to 120 hours after drug administration for pharmacokinetic analysis and the assessment of DPP IV activity, and blood samples were collected up to 2 hours after each meal until the next morning of drug administration to evaluate active GLP-1, glucose, and insulin levels. RESULTS: Seventy-two subjects, aged 20 to 39 years and weighing 52.1 to 79.8 kg, participated in this study. Twenty-one adverse events were reported; all were mild, and all subjects recovered spontaneously. DA-1229 reached a peak at 3.0 to 5.5 hours after a single oral dose and the concentrations declined, with a terminal t(½) from 32.5 to 39.8 hours. The %CV of C(max) and AUC(0-last) ranged from 11.1% to 54.6%. Dose-proportional pharmacokinetics were confirmed within the dose range by using a linear regression analysis, and the 95% CIs of the slope of the log-transformed C(max) and AUC(0-last) included 1.0. The pharmacokinetics of DA-1229 were unchanged by food. The degree of DPP IV inhibition was dependent on the dose, and groups receiving ≥10 mg exhibited >80% DPP IV inhibition for >24 hours. The %CV of the time of the last quantifiable concentration ranged from 4.6% to 15.2%. C(max) of active GLP-1 was achieved at 30 minutes after meal intake. The active GLP-1 levels were enhanced in groups receiving ≥5 mg. There were no changes in the glucose and insulin levels after DA-1229 administration. CONCLUSIONS: DA-1229 was well tolerated within the dose range of 1.25 to 60 mg. DA-1229 pharmacokinetics suggested dose proportionality, and dose-dependent DPP IV inhibition was exhibited. ClinicalTrials.gov identifier: NCT00961025.

A positron emission tomography microdosing study with sertraline in healthy volunteers.

OBJECTIVE: This study explored microdosing methods for evaluating the distribution and pharmacokinetics (PK) of a central nervous system (CNS) drug candidate. METHODS: We used sertraline as a model drug. In this open-label, one-arm, three-period, multiple-dosing study, 10 healthy male volunteers received 6-day administrations of sertraline at doses of 5, 25 or 50 mg/d in three different periods. Before the first dose of Period 1, and 24 h after the last dose of each period, an intravenous bolus of [11C]sertraline was injected for positron emission tomography (PET) scanning. After the sixth dose in each period, serial blood samples were collected at scheduled intervals over 48 h; then serum sertraline concentrations were determined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Sertraline was distributed in the brain within 20 min, and it was highly distributed in the putamen, cingulate, and thalamus. Linearity in steady-state Cmax and AUClast were observed in the 5 - 50 mg dose range. The results suggested that microdosing with PET was a useful method for exploring the bloodbrain- barrier penetration and distribution of a candidate CNS drug. CONCLUSIONS: This study described a microdosing method that combined PET with LC-MS/MS for determining the brain distribution and PK characteristics of a CNS drug candidate.

Comparison of the bioavailability and tolerability of fixed-dose combination glimepiride/metformin 2/500-mg tablets versus separate tablets: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy Korean volunteers.

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.

Comparative pharmacokinetic evaluation of two formulations of bicalutamide 50-mg tablets: an open-label, randomized-sequence, single-dose, two-period crossover study in healthy Korean male volunteers.

BACKGROUND: Bicalutamide is an oral nonsteroidal antiandrogen drug used during hormone ablation therapy for prostate cancer. A new generic formulation of bicalutamide has been developed. OBJECTIVES: This study was conducted to meet Korean and US regulatory requirements for the marketing of the generic 50-mg tablet formulation of bicalutamide. To this end, the pharmacokinetic properties of the new (test) formulation were compared with those of the currently marketed (reference) formulation. Tolerability was also evaluated. METHODS: An open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy Korean male volunteers. Subjects received either the test or reference formulation of bicalutamide 50-mg tablets in the first period and crossed over to the alternative formulation in the second period. Serial blood samples for pharmacokinetic analysis were taken over 672 hours after dosing. Plasma concentrations of bicalutamide were measured by HPLC-MS/MS. Pharmacokinetic parameters, including AUC(0-672h), were determined by noncompartmental analysis. Log-transformed C(max) and AUC(0-672h) for the 2 formulations were compared. Tolerability was monitored based on laboratory tests, ECGs, vital signs, and physical examinations. RESULTS: Of the 34 subjects initially enrolled, 33 completed the study. The mean (SD) age, height, and weight of participants were 25.8 (4.1) years, 173.6 (5.7) cm, and 68.9 (7.8) kg, respectively. The median T(max) was 36.0 hours for both formulations. The mean (SD) t(1/2), C(max), and AUC(0-672h) for the reference formulation were 135.4 (28.6) hours, 933.2 (169.2) microg/L, and 215,680.1 (48,753.4) microg x h/L, respectively. Corresponding values for the test formulation were 134.3 (30.7) hours, 946.7 (179.9) microg/L, and 221,708.8 (54,935.1) microg x h/L. The 90% CIs for the mean ratios (test/reference) of log-transformed C(max) and AUC(0-672h) were 0.97 to 1.06 and 0.98 to 1.07, respectively. Twelve adverse events were reported for each formulation, none of which were considered drug related in the test-formulation group and 4 of which were considered drug related in the reference-formulation group (3 cases of headache, 1 case of erythematous rash). CONCLUSIONS: In this single-dose study in healthy Korean male subjects, the new formulation of bicalutamide 50-mg tablets met Korean and US regulatory criteria for assumption of bioequivalence with the currently marketed formulation. Both formulations were generally well tolerated, with no clinically relevant safety concerns.

The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study.

BACKGROUND: Mirodenafil, a phosphodiesterase 5 inhibitor reported to be effective in the treatment of erectile dysfunction, is metabolized by cytochrome P450 (CYP) 3A4 to the active metabolite N-dehydroxyethyl mirodenafil. Mirodenafil may have drug-drug interactions with ketoconazole and/or rifampicin. OBJECTIVE: The aim of this study was to investigate the effects of a potent inhibitor (ketoconazole) and inducer (rifampicin) of the CYP3A4 isozyme on the pharmacokinetics of mirodenafil to meet the regulatory requirements for the marketing of mirodenafil in Korea. METHODS: An open-label, 1-sequence, 3-period, 3-treatment crossover study was conducted over 22 days in healthy Korean male volunteers. Each subject received 100 mg of mirodenafil in each of 3 study periods: mirodenafil alone (period 1); mirodenafil after pretreatment with ketoconazole 400 mg once daily for 3 days (period 2); and mirodenafil after pretreatment with rifampicin 600 mg once daily for 10 days (period 3). Serial blood samples were collected for pharmacokinetic analysis after the administration of mirodenafil in each study period. Plasma concentration-time data for mirodenafil and its major metabolite, N-dehydroxyethyl mirodenafil, were determined using LC-MS/MS and analyzed by a noncompartmental method. The results for mirodenafil coadministration with either ketoconazole or rifampicin were compared with those for mirodenafil alone. Adverse events (AEs) were identified by asking general health-related questions of the subjects, by physical examination, and by subject self-report throughout the study period. RESULTS: Nineteen subjects were enrolled (mean [SD] age, 23.2 [2.76] years [range, 19-29 years]; weight, 69.3 [6.50] kg [range, 61.0-84.0 kg]; body mass index, 22.4 [1.77] kg/m(2) [range, 20.0-26.0 kg/m(2)]) and 18 subjects completed the study. One subject discontinued the study due to protocol violation and was replaced. The AUC(0-infinity) of mirodenafil increased 5.04-fold (90% CI, 3.78-6.72) and the metabolic ratio decreased 0.21-fold after pretreatment with ketoconazole compared with mirodenafil alone. After pretreatment with rifampicin, the AUC(0-infinity) of mirodenafil decreased 0.03-fold (90% CI, 0.02-0.05) and the metabolic ratio increased 2.9-fold. Twelve cases of headache, 6 of nasal congestion, 2 of feeling hot, 2 of epistaxis, and 1 each of dizziness, nausea, and somnolence were considered to be related to administration of mirodenafil. Twenty-eight AEs were reported in period 2 (in 68.4% of subjects), during which systemic exposure to mirodenafil was highest, whereas 7 AEs were reported in period 1 (in 31.6% of subjects) and 5 AEs in period 3 (in 16.7% of subjects). CONCLUSION: In these healthy Korean male volunteers, the coadministration of ketoconazole and rifampicin resulted in significant changes in systemic exposure to mirodenafil.

Panax ginseng increases hypoxia-induced down-regulated cellular response related genes in human neuroblastoma cells, SK-N-MC.

BACKGROUND: Many studies have suggested that hypoxia plays a crucial role in the pathogenesis of various neurological disorders. To determine protective effect of Panax ginseng (PG) on hypoxia (0.1% O(2))-induced cell death in human neuroblastoma cells SK-N-MC, we profiled the gene expression among hypoxia, PG-treated hypoxia and normoxia groups. METHODS: To determine protective effect on hypoxia-induced cytotoxicity of PG, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We compared the gene expression profiles among hypoxia, PG-treated hypoxia (100 mug/ml, 6 hours) and normoxia groups using 8K human cDNA microarray analysis. Additionally, in order to identify differentially expressed genes between hypoxia and PG-treated hypoxia groups, hierarchical clustering of genes was also performed. RESULTS: MTT assay showed that PG protected hypoxia-induced cell death. In cDNA microarray analysis, hypoxia remarkably down-regulated IGF-II mRNA-binding protein 3 (IMP-3), integrin alpha 2 (ITGA2), syndecan binding protein (SDCBP), insulin-like growth factor binding protein 3 (IGBP3) and M-phase phosphoprotein 10 (MPHOSPH10), belonging to category of cellular physiologic response (global M<-3.5). In cluster analysis, 1428 genes exhibited differential expression levels between hypoxia and PG-treated hypoxia groups. Of them, the expressions of 11 genes were increased more than two-fold by PG treatment compared to those in hypoxia group. Particularly, of 11 genes, the expression levels of cellular physiologic response related genes such as MPHOSPH10, IMP-3 and SDCBP, which markedly down-regulated by hypoxia, are increased more than four-fold by PG treatment, compared to hypoxia group. CONCLUSION: In summary, hypoxia induced down-regulation of cellular physiologic response related genes in human neuroblastoma cells, SK-N-MC, and PG ameliorated the hypoxia-induced down-regulation of such genes. These results indicate possible usage of PG in hypoxia-induced neuronal injury including ischemia, trauma and degenerative diseases.

Neuroprotective effect by Dammishimgyu-herbal acupuncture against H(2)O(2)-induced apoptosis in human neuroblastoma, SH-SY5Y cells.

BACKGROUND: The free radical is involved in neuronal cell death in human neurodegenerative disease. Dammishimgyu (DMSG)-herbal acupuncture has been used to treat neurological disorders in Korea. The present study was aimed to investigate the neuroprotective effect of DMSG-herbal acupuncture against H(2)O(2)-induced apoptosis in human neuroblastoma cell line, SH-SY5Y. METHODS: The neuroprotective effect of DMSG-herbal acupuncture on H(2)O(2) induced apoptosis was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, reverse transcription-polymerase chain reaction (RT-PCR), western blots and nitrite assay. RESULTS: In this study, 100 microM H(2)O(2)-treated cells decreased the cell viability with apoptotic features and increased the production of nitric oxide (NO). However, 0.1% DMSG treatment after exposure to 100 microM H(2)O(2) inhibited both H(2)O(2)-stimulated mRNA and protein expressions of BCL2-associated X protein (BAX) and caspase 3 apoptosis-related cysteine peptidase (CASP3). In addition, 0.1% DMSG treatment inhibited the increased NO production induced by H(2)O(2). CONCLUSION: These results suggest that DMSG-herbal acupuncture shows protective effect against H(2)O(2)-induced neuronal damage.

Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4.

AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4. METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed. RESULTS: In this study, cytotoxic effect of OPC on SNU-C4 cells appeared in a dose-dependent manner. OPC treatment (100 microg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 microg/mL) increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 microg/mL) compared with control. CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells.

AIM: The genes were divided into seven categories according to biological function; apoptosis-related, immune response-related, signal transduction-related, cell cycle-related, cell growth-related, stress response-related and transcription-related genes. METHODS: We compared the gene expression profiles of SNU-C4 cells between amygdalin-treated (5 mg/mL, 24 h) and non-treated groups using cDNA microarray analysis. We selected genes downregulated in cDNA microarray and investigated mRNA levels of the genes by RT-PCR. RESULTS: Microarray showed that amygdalin downregulated especially genes belonging to cell cycle category: exonuclease 1 (EXO1), ATP-binding cassette, sub-family F, member 2 (ABCF2), MRE11 meiotic recombination 11 homolog A (MRE11A), topoisomerase (DNA) I (TOP1), and FK506 binding protein 12-rapamycin-associated protein 1 (FRAP1). RT-PCR analysis revealed that mRNA levels of these genes were also decreased by amygdalin treatment in SNU-C4 human colon cancer cells. CONCLUSION: These results suggest that amygdalin have an anticancer effect via downregulation of cell cycle-related genes in SNU-C4 human colon cancer cells, and might be used for therapeutic anticancer drug.