The Effect of Luteolin on the Modulation of Vascular Contractility via ROCK and CPI-17 Inactivation

In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited in-crease in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.

Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells

Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 μM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

The Effect of Galangin on the Regulation of Vascular Contractility via the Holoenzyme Reactivation Suppressing ROCK/CPI-17 rather than PKC/CPI-17

In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway.Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoridedependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

A Study of Irritable Bowel Syndrome and Stress on Female College Students in Korea

OBJECTIVE: The purpose of this study was to provide a database for making better decisions of the treatment of the irritable bowel syndrome (IBS) patient, and for improving the recognition of IBS in the Korean society. METHODS: The survey was conducted on 174 female college students in Korea from January 2017 to January 2018. Out of the total students surveyed, 160 questionnaires were analyzed after excluding 14 uncompleted questionnaires. RESULTS: Based on the survey, the prevalence of IBS among female college students in Korea was found to be 13.8%. Statistically, the results proved that there were significant differences in the stress levels between the students with IBS and non-IBS diagnosed by ROME IV criteria. Students with IBS had higher stress levels than students without the ailment. CONCLUSIONS: Based on this study, stress management related treatment should be actively considered. Furthermore, it is necessary to develop more efficient and updated guidelines for the treatment of IBS and new patient care programs.

The Awareness of Contraception and Experience of Oral Contraceptives among North Korean Defector Women in Republic of Korea

OBJECTIVE: This study attempts to gauge the necessity of contraceptive education for women defecting from North Korea (NKDWs). METHODS: We conducted in-depth interviews with six NKDWs who had lived in the Republic of Korea (ROK) for more than three years, to understand the subjects' perceptions, experiences, and opinions regarding contraception. Thematic analyses were performed using qualitative data provided in the survey results. RESULTS: Before their defections from North Korea, none of the NKDWs had received any sex education. Loop is the only contraceptive method available to married women in ROK. After defection, NKDWs were provided information about contraceptive options available in China, but they could not fully understand this information. Furthermore, the information they received was not accurate. Thus, NKDWs had a high need for contraceptive sex education. As per our survey, their preferred education method was at least 3 lessons plus 1 : 1 counseling, as necessary. CONCLUSION: This study indicates that a necessity exists for development of a sex education program for NKDWs to enhance their contraceptive knowledge. Thus, government and health managers have a role to play in developing such a program.

An Overview of the Risk Sharing Management in Korean National Health Insurance, Focused on the Effect of the Patient Access and Insurance Finance

OBJECTIVE: This study examined the Risk Sharing Agreement (RSA) on pharmaceutical pricing system in Korean national health insurance. Through RSA, the insurer was able to maintain the principles in the price listing process while managing the budget effectively and improving patient access to new drugs. Despite these positive effects, there are still issues raised by some stakeholders, such as lack of transparency in the listing process and doubts about its effectiveness. Therefore, we investigated the impacts of RSA on national health insurance financing and patient access to analyze the effects of RSA. METHODS: The impact of RSA was investigated by analyzing the health insurance claims data for 2014~2016. The degree of improvement in patient access was determined by the decreased amount of patients' payment. RESULTS: Results showed that the financial impact of RSA was not significant and patients' access to the new drug greatly improved. CONCLUSION: These results show that RSA is a good system for improving patient access to new drugs without additional expense on insurance.

Pharmacists' Perception for the Current and Future Pharmaceutical Services

OBJECTIVE: We conducted a survey to understand the current state of pharmacy services and pharmacists' thoughts in the future of the community pharmacy setting. METHODS: A questionnaire was distributed to 229 pharmacists and gathered from 95 respondents. RESULTS: We asked to pharmacists about what the ideal pharmacy duty should be in the next 10 years at the community pharmacy setting in Korea. For this question, the respondents said drug counselling (19.4%), dispensing (13.8%), longterm care of chronic disease and healthcare education (12.8%), and OTC counselling (11.5%). When asked about how much time they were spending doing certain tasks in the pharmacy, the main tasks were dispensing (23.5%), counselling (17.1%), prescription review (10.1%), and OTC counselling (5.5%). When asked about what the most important duty of a pharmacist was, medication counselling (45.4%) was the most important task that they identified and the reasons for not being able to fulfill this role properly was time shortage (78.9%) followed by the lack of counselling spaces, up-to-date knowledges, and focus on financial gains over patient counselling. CONCLUSION: Korean pharmacists are mainly focusing on dispensing in their daily work. Their basic responsibilities can be easily mechanized over the next few years, but the social expectations of disease-prevention and public health promotion both in current and future can not be replaced by such mechanical measures. Therefore, pharmaceutical services in Korea should be developed in more diverse and professional ways.

Development and Clinical Use of Assessment Indicators for Improving Medication Adherence of Elderly Residents in Nursing Home

BACKGROUND: South Korea is rapidly being an aging-society and the demand of long-term care insurance services for elderly patients is rising. In addition, because the elderly taking multiple medicines, the adherence is lowered and the adverse events are easily occurred. Therefore, many are interested in introducing the geriatric pharmacy specialist to manage this situation. PURPOSE: By applying a similar program such as the geriatric pharmacy specialist working in nursing home, we conducted this study to evaluate the potential contribution to both the health insurance services and financial savings for the elderly patients. METHODS: We conducted a trial in an elderly nursing home to collaborate between doctor and pharmacist making a checklist for improving medication adherence and establish a consultation system. Also we applied a smart phone application in the pharmaceutical care processes. RESULTS: Thereby completing the drug therapy related checklist apply to nursing facilities in South Korea. And we got a performance that improves medication adherence when used in the clinical practice settings. CONCLUSION: By introducing a training program of pharmacy care managers and geriatric professionals such as the United States and Japan, we revealed the elderly nursing home residents and vulnerable elderly people living alone were improved the medication adherence and it will contributed to the health and quality of life of the patients.

A Study on the Statistical Method for the Target Component of a Glucose-lowering Functional Material in Extracts of Evening Primerose Seeds

BACKGROUND: The use of the extracts from evening primrose seeds as a health functional food has been gradually increased. Therefore, the monitoring and screening process has been considerably required for its quality control. OBJECTIVE: This study aimed to estimate the measurement uncertainty associated with determination of penta-o-galloyl β-D-glucose (PGG) in extracts from evening primrose seeds by high-performance liquid chromatography. METHODS: The sources of measurement uncertainty was expressed in accordance with mathematical/statistical theories of GUM & EURACHEM Guide. The expanded uncertainty was calculated by using the relative standard uncertainty between analytical result and sources of uncertainty in measurement (sample weight, final volume, extraction volume, standard solution, matrix and instrument etc). RESULTS: In the results of 95% confidence interval, the uncertainty in measurement was 10,253.34 ± 1,844.50 µg/kg (k = 2.0). CONCLUSION: In this study, it showed that the value of uncertainty in measurement for determination of PGG in extracts from evening primrose seeds by HPLC has about 18.0% influence on PGG contents of the analytical results. The results would be very useful for the monitoring and screening of evening primrose seeds marketed in Korea for its quality control as dietary supplement.

Survey on Pharmacist's Awareness of E-commerce for Non-prescription Medicine

OBJECTIVE: Online pharmacies were introduced in some countries such as United States of America or Canada. They can provide benefits to consumer because they can buy and take conveniently drugs without limitation of location or time. In Korea, online pharmacies are illegal and only pharmacists can sell drugs to consumers or patients. Therefore, we investigated the knowledge of online pharmacy and the possible problem in Korea to survey pharmacists. METHODS: We developed questionnaire based on previous articles about online pharmacy and surveyed nation-wide pharmacists by mail or e-mail. The data was analyzed by SPSS and Microsoft Excel. P-values less than 0.05 were statistically significant. RESULTS: 175 pharmacists involved in this study. About introduction of online pharmacies, 53.1% were opposition while 10.3% were approval and 36.6% were conditional. Although online pharmacies were introduced, 46.3% pharmacists do not have a plan to start online pharmacy. However, the approval and tends about starting online pharmacies were higher in younger pharmacists (20s, 30s) (p < 0.05). The criteria of permission about opening online pharmacies were 100% pharmacist license regardless of holding off-line pharmacy. 53.7% pharmacists responded education about taking medication is impossible. When online pharmacies are introduced, 65.1% pharmacists responded traditional pharmacies are affected negatively. Pharmacists concerned that the competition with large-sized distribution corporations, reduced reliance between pharmacists and patients, illegal transaction of counterfeit drugs, increased misuse of drugs. CONCLUSION: These results showed that Korea pharmacists have negative standard on online pharmacies. Therefore it is required to be more cautious before introducing online pharmacy and it need strict watching system and continuous education and study for safety after introducing online pharmacy.

Developing Prevention System of Overseas Infectious Disease Based on MERS and Zika Virus Outbreak

OBJECTIVE: The outbreak of Middle East Respiratory Syndrome (MERS) started in South Korea in May 2015 and the end of crisis was declared in December 2015 by Korea Centers of Disease Control and Prevention (KCDC). However, Zika virus emerged in less than 2 months following MERS and showed higher mortality than other countries. This study is to assess the current prevention system of overseas infectious diseases, based on MERS and Zika virus outbreak and to suggest effective response system for the future. METHODS: We conducted two surveys on medical specialists working at tertiary general hospitals regarding the effectiveness of responding system by KCDC against MERS and Zika virus and education in individual medical institutions using 5-Likert points. Response system was examined in three different periods as initial period, spreading period, and post disease period. RESULTS: Although medical specialists received the notifications in initial period, no practical prevention was proven to be placed in responding stage by medical facilities (averagely 3.5/5 points in total and sub-analyses). During spreading period, there were several academic seminars conducted, which were evaluated as helpful. In post disease period, all answered that there were changes on patient treatment in all medical facilities, with mainly report system and the treatment regulations in case of suspicious patients for infection. Only 49% respondents answered positive on the possibility of initial responses. For questionnaire items regarding Zika virus, all answered that there were notifications prior to the first outbreak of the infected patient. Eighty% of respondents were aware of 'the Guideline system for traveling to dangerous areas', and answered that the system was moderately effective (averagely 3.8/5 points in total). For the effectiveness of prevention measures for foreign novel disease by KCDC, the average point was 3.0 in both of total and sub-analyses. CONCLUSION: There is not enough response system to prevent infectious disease in medical institutional and governmental levels in Korea. It would warrant the modification of overall medical system to improve preventive measures for initial spread of such diseases.

Prophylactic Effect of Pegfilgrastim on Febrile Neutropenia in Patients with Non-Hodgikin's Lymphoma

OBJECTIVE: Pegfilgrastim is recently introduced that is long acting G-CSF for prophylaxis of febrile neutropenia. Treatment of non-Hodgikin's lymphoma (NHL) with R-CHOP is classified with relative high risk of febrile neutropenia. The study evaluated the prophylactic effect of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-CHOP of patient in NHL. And the risk factors associated with the incidence of FN and related events were evaluated. METHODS: This retrospective study reviews the Electronic Medical Record of 68 NHL patients who received R-CHOP chemotherapy in single center between September 2013 and August 2014. These patients were classified who receive prophylaxis pegfilgrastim or no prophylaxis. RESULTS: Sixty eight patients received R-CHOP with NHL. In 144 cycles of patients receiving pegfilgrastim, compared with no prophylaxis 178 cycles, had a lower incidence of febrile neutropenia (5.5% vs. 23.6%, p = 0.001), grade 3 or grade 4 neutropenia (14.4% vs. 89.8%, p or = 65 (OR: 5.87, 95% CI 1.07-32.27, p = 0.042), IPI > or = 3 (OR: 7.2, 95% CI 1.31-39.6, p = 0.023), S.alb < 3.5 g/dL (OR: 31.01, 95% CI 6.32-152.17, p < 0.0001). In multiple logistic regression analysis, lower baseline serum albumin (OR: 21.1, 95% CI 3.8-116.98, p = 0.001) was significantly associated with occurrence of febrile neutropenia. CONCLUSION: The study recommends prophylactic pegfilgrastim through risk assessment of febrile neutropenia in patients with non-Hodgikin's lymphoma receiving R-CHOP.

Survey of Correlations on the Drug Use Patterns between Children and Their Parents

BACKGROUND: It is thought that drug use of parents is related to that of young children. The status of drug among young children's parents and a correlation of with parents and their children on drug use was surveyed by questionnaire. METHOD: The questionnaire is composed of 34 items, and the data was collected by 108 parents of young children from March to April of 2012. RESULTS: On the basis of the analysis results, the following conclusions were drawn. About half of parents thought the minimum use of drug was better for health, and 44% parents thought drug is essential for cure. When parents had queries on prescription, they mostly consult with doctors and pharmacists. Most parents had a household medicine. A fever reducer was the most common household medicine (92.5%). They pick the household medicine by consulting with pharmacist. Parents usually checked the expiration date of drug before they use and they dumped the drugs when the expiration date was due (82.4%). Over half of young children and their parents took a dietary supplements. They got an information about a dietary supplement by associates (30.5%) and internet (19.4%). Most parents tried to follow the directions as prescribed. However, more than half of the parents stopped taking the drug when the symptoms disappeared. CONCLUSION: Drug use of parents and that of young children had a very strong positive correlation, suggesting that correct drug use of parents have an impact on their young children's drug use.

Utility Analysis for Pegfilgrastim in DLBCL Patients on R-CHOP Regimen

OBJECTIVE: This study was designed to compare pegfilgrastim and filgrastim in diffuse large B-cell lymphoma (DLBCL) patients treated with a rituximab with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen in terms of clinical efficacy and cost-effectiveness. METHOD: Clinical efficacy was measured by trough level of absolute neutrophil count (ANC), days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, duration of ANC recovery to baseline value, days of ANC less than 0.5 x 109 cells/L, and difference of peak and trough level of ANC during 1 cycle of R-CHOP regimen. To evaluate cost-effectiveness, total prices of used filgrastim and pegfilgrastim within 1 cycle of R-CHOP were analyzed. RESULTS: In terms of clinical efficacy, trough level of ANC and days to ANC recovery showed statistical significance. The median trough levels of ANC with administration of filgrastim and pegfilgrastim were 0.18 and 1.94 (p = 0.021), respectively, and the median durations of ANC recovery to baseline value were 5.5 days and 2 days (p = 0.023), respectively. For the median days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, days of ANC less than 0.5 x 109 cells/L, and difference of peak and trough level of ANC during 1 cycle of R-CHOP, the pegfilgrastim group performed better than the filgrastim group. However the difference was not statistically significant. In terms of overall expense during 1 cycle of R-CHOP, pegfilgrastim is about 3.43 times more expensive than filgrastim. CONCLUSION: Pegfilgrastim is more efficient than filgrastim in terms of clinical efficacy. In terms of prices, pegfilgrastim is more expensive than filgrastim for patients, but it is more convenient in clinical use. Therefore, pegfilgrastim should be the preferred choice of G-CSF for neutropenic patients. Further comparative study of pegfilgrastim and filgrastim is needed.

Leading Study for the Restoration of Pediatric Immunization Systems in North Korea following Reunification of Korean Peninsula

BACKGROUND: 8,000 children in North Korea died before they reached the 1 year after births in 2013. The high mortality rate of children under five years of age is mainly caused by infectious diseases and malnutrition. The need for national pediatric immunization and supply of vaccines will be vital when the abrupt reunification occurs. OBJECTIVE: The purpose of this study is to scrutinize the pediatric immunization coverage of North Korea. Additionally it is to estimate the amount and the costs needed to vaccinate. METHODS: The target population is the children of North Korea. The method is based on a pre-survey and an interview of North Korea defectors. The target interviewees searched for are as follows; doctors, teachers, and others. The interview includes questions on mortality rates and immunization coverage. The analysis is largely based on the statements of the health care providers within the selected group. RESULTS: The interviewees are 8; 7 female and 1 male. The birth years range from 1956 to 1982. 3 out of 8 are former health care providers; a doctor, a pharmacist, and a nurse. The morbidity rate of infectious diseases exceeds the data from WHO. The immunization coverage is nearly 0% after 1980s. In order to ensure the welfare of North Korean children, at least 8,234,000 vaccine doses, requiring over 105 million U.S. dollars, are needed. CONCLUSION: The morbidity rate of infectious disease in North Korea is conspicuous. The preparation for supply and expenditure of vaccines is vital.

The Factors Related to the Intention of Hospital Pharmacists for taking the Role of a Preceptor

BACKGROUND: Pharmacy schools newly adopted a 6-year program strengthening clinical knowledge since 2011 in Korea. The clinical training under the guidance of preceptors at hospital sites is a requisite for pharmacy students during the last year of undergraduate course. It has been rarely studied on the hospital pharmacists' perspective regarding being a preceptor or teaching pharmacy students. OBJECTIVES: This study aimed to examine the hospital pharmacists' intention toward student training and to identify the relevant factors among the individual pharmacists' characteristics and working environment within the theoretical frame of the Theory of Planned Behavior (TPB). METHOD: A mail-survey was conducted for pharmacists working in tertiary hospitals in Seoul and Incheon. The survey questionnaire consisting of 131 questions with a 5-likert scale was developed for investigating pharmacists' attitude, subjective norm, perceived behavioral control and the intention to teach pharmacy students as well as other demographic variables. To estimate the construct validity of components, factor analysis was conducted and Cronbach's alpha was calculated to estimate the reliability of the observed variables. Statistical analyses of one-way variance analysis and multiple regression analysis were performed using SPSS 18.0. RESULTS: The survey response rate was 53% (116/210) and the three constructs of attitude (r = .519), subjective norm (r = .233) and perceived control (r = .392) have appropriate correlations with the intention, proving the appropriateness of using the TPB model. Pharmacists working in inpatient (mean = 3.45) and outpatient clinics (mean = 3.34) generally showed positive intention for teaching. The attitude (beta = .432, p < 0.01) and perceived control (beta = .270, p < .01) constructs were significant predictors of the intention. Both age (r = 0.246, p = 0.017) and length of career (r = 0.310, p = 0.002) were positively related with the perceived control. CONCLUSION: Hospital pharmacists showed generally positive intention to provide student training in spite of the concern on their limited perceived behavioral control. Future research to find the actual barriers pharmacists faced in educating students need to be conducted.

Effects of Fluvastatin on the Pharmacokinetics of Repaglinide: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Fluvastatin

The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration(IC50) of 4.1 microM and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the AUC0-infinity of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.