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Objective@#Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization. @*Methods@#After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay. The tubulin polymerization rate was also measured. @*Results@#We observed increased and decreased expression of acetylated and tyrosinated α-tubulin, respectively, decreased expression of p-STMN1 (Ser16) and increased expression of p-STMN1 (Ser25), p-STMN2 (Ser73) and GRP-78 and CHOP in the prefrontal cortex and/or hippocampus of defeated mice. A reduced tubulin polymerization rate was observed in the Sus group compared to the Uns and Con groups. @*Conclusion@#Our findings suggest that SDS has detrimental effects on MT stability, and a lower tubulin polymerization rate could be a molecular marker for susceptibility to SDS.
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BACKGROUND@#With the globalization of drug development, multi-regional clinical trials (MRCTs) have emerged to facilitate rapid availability of medicines to patients worldwide. The present study aimed to has explored attitudes and perceptions towards adopting the Korean MRCT guideline.@*METHODS@#An online survey, consisting of 16 questions, classified into two subjects, was administered to stakeholders in Korea. Most quantitative components were measured using the Likert scales. A content analysis of the qualitative components was carried out to identify the keywords in open-ended responses.@*RESULTS@#A total of 94 survey responses were analyzed: 51 participants from pharmaceutical companies, 11 from clinical research organizations, and 21 from clinical trial centers. The content of the guideline was rated as appropriate for clarity, acceptability, and applicability (96.8, 96.8, and 93.6%, respectively). The local environmental impact of the systemic/political, academic/technical, and industrial/economical aspects of the guideline was rated as appropriate at 95.7, 97.9, and 91.5%, respectively. The suggested adoption period was 1~2 years (40, 42.6%). The concept and individuals' domestic circumstances were the key problems affecting the clarity, applicability, and local environmental impact of the guideline.@*CONCLUSION@#The Korean MRCT guideline was well-developed. Their overall impact on the local environmental impact of MRCTs in Korea was expected to be beneficial, but methods are needed to minimize the negative impacts. The findings of this study can inform the priorities for the future adoption of the guideline in Korea.
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BACKGROUND: Although the importance of pharmaceutical care service has been growing to meet the needs of customers with the improvement of clinical and humanistic outcomes, there was not a systematic strategy to promote research in Korea. The aim of this study was to suggest the core agendas for pharmaceutical care services research and development (R&D) considering priorities. METHODS: Based on desk researches, we developed R&D agendas for the needs of improving pharmaceutical care services in the area of institution, community, and public health. To determine the priority of agendas in developing pharmaceutical care service, analytic hierarchy process (AHP) analysis was performed by the 14 experts. Criteria and subcriteria were assessed for significance by pairwise comparisons. Then, agendas were evaluated for importance according to each subcriteria, and rank ordered considering the weight calculated by multiplying the importance scores of the criteria and the subcriteria. RESULTS: We derived 25 agendas including 13 for institutional pharmaceutical care service, 8 for community pharmaceutical care service, and 4 for public-health related pharmaceutical care service. AHP model was constructed based on 4 criteria and 8 subcriteria by a hierarchical structure. From the AHP survey, the ‘Development of pharmaceutical care service for metabolic and chronic disease’ agenda accounted for the highest priority. CONCLUSION: We have developed the R&D agendas of the pharmaceutical care service which should be promoted. The results should be utilized by the government to nationally support the development of the standards and relevant regulations related to pharmaceutical care services in Korea.
Subject(s)
Korea , Pharmaceutical Services , Public Health , Social Control, FormalABSTRACT
BACKGROUND: Although a growing number of guidelines and clinical researches are available for immunosuppressive treatment of post-transplantation, there is no clinical practice guideline for the care of kidney transplant recipients in Korea. Selection of a researchable question is the most important step in conducting qualified guideline development. Thus, we aimed to formulate key questions for Korean guideline to aid clinical decision-making for immunosuppressive treatment. METHODS: Based on previous published guidelines review, a first survey was constructed with 29 questions in the range of immunosuppressive treatments. The experts were asked to rate the clinical importance of the question using a 5-point Likert scale. The questions reached 60% or more from the first survey and additional new questions were included in the second survey. In analyzing the responses to items rated on the 9-point scale, consensus agreement on each question was defined as 75% or more of experts rating 7 to 9. RESULTS: In the first survey, 50 experts were included. Among the 29 questions, 27 were derived to get 60% or more importance and 3 new questions were additionally identified. Through the second survey, 9 questions were selected that experts reached consensus on 75% and over of the options. Finally, we developed key questions using PICO (patient, intervention, comparison, and outcome) methodology. CONCLUSION: The experts reached a high level of consensus on many of key questions in the survey. Final key questions provide direction for developing clinical practice guideline in the immunosuppressive treatment of transplantation.
Subject(s)
Clinical Decision-Making , Consensus , Kidney Transplantation , Kidney , Korea , Transplant RecipientsABSTRACT
OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. METHODS: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. RESULTS: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than solublereceptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). CONCLUSION: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.
Subject(s)
Humans , Arthritis, Rheumatoid , Incidence , Odds Ratio , Tuberculosis , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. METHODS: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. RESULTS: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. CONCLUSION: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.
Subject(s)
China , Developed Countries , Sample Size , Social Control, Formal , United States Food and Drug AdministrationABSTRACT
About 40% of pregnant women are exposed to one or more kinds of medications including multivitamins during their early pregnancy period. And some of those medications are essential for the mother's health throughout full time of pregnancy. But most of clinical trial for the medicine cannot include the pregnant women because of its uncertain effect on fetus. In this circumstances, the medication can be researched by retrospective study through establishing pregnancy exposure registries. In this study, we aimed to make evidence of fetal safety and risk of many biopharmaceutical products that can help clinician & pregnant women. It is important to enroll the pregnant women who had medication exposure in her early pregnancy without any selective biases. And It should include enough population size and proper data. In addition, pregnancy outcome including the major & minor anomalies of fetus following the exposure of medications in pregnancy must be evaluated by regulated standard guideline. USA & European Union had already published the registry of pregnant women and it really helpful for safe prescription in pregnant women. So It is strongly suggested that this registry will have a great influence on determining the safety and risk of many medications in Korean pregnant women.
Subject(s)
Female , Humans , Pregnancy , Bias , European Union , Fetus , Population Density , Pregnancy Outcome , Pregnant Women , Prescriptions , Registries , Retrospective StudiesABSTRACT
The thalidomide tragedy in the 1960s has resulted in a perpetuation of a certain perception amongst physicians and pregnant women that the use of medication during pregnancy is a potential teratogen. Consequently, physicians hesitate in prescribing medication to pregnant women. In addition, pregnant women often refuse medication despite therapeutic necessity because of this existing perception. Recently there have been frequent adverse pregnancy outcomes related to the recurrence of chronic diseases, such as hypertension and diabetes, following pregnancy in older women. And there are lots of unnecessary termination of pregnancy due to the of information of medication exposed to medication following over 50% of unintended pregnancy. In light of this, better dissemination of information regarding the safe usage of medication for pregnant women is required. This would not only be cost-effective in terms of medical expenditure, but also prove beneficial for the treatment of diseases. In addition, Korea needs to adapt to the increasing changes of the international information system regarding supporting the safe usage of medication during pregnancy. An example of this is shown by the recent changes to the labeling of medication by the United States Food and Drug Administration. The new labeling includes information on the risk of usage, rather than just an arbitrary alphabetic classification of B, C, D, or X. Furthermore, this information is limited in Korea because of the lack of research, which in turn is due to several limitations on ethics and methodology, as well as present regulations on the research of pregnant women. From this, we can learn that government support is critical for the establishment of research so that we can alter the perception that all medication is harmful to pregnant women.
Subject(s)
Female , Humans , Pregnancy , Chronic Disease , Classification , Ethics , Health Expenditures , Hypertension , Information Systems , Korea , Pregnancy Outcome , Pregnant Women , Recurrence , Social Control, Formal , Thalidomide , United States Food and Drug AdministrationABSTRACT
Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.
Subject(s)
Adenocarcinoma , Bile Ducts , Carcinoma, Squamous Cell , Cholangiocarcinoma , Colon , Epigenomics , Genome , Individuality , Kidney , Liver , Lung , MicroRNAs , Pharmacogenetics , RNA, MessengerABSTRACT
BACKGROUND: Pharmacy curriculum change was made from a 4-year program to a 2+4 year program in year 2009 in Korea. The change has resulted in more educational exposures on patient-centered practice environments for about 1,400 hours in the last year of the professional pharmacy program. When the Middle East Respiratory Syndrome (MERS) outbreak hit Seoul and suburban areas and propagated to other provinces in Korea, emergency response to avoid student infection in the pharmacy practice sites became an urgent issue. While other health professional programs such as medicine and nursing had activated emergency preparedness manuals, timely and clear guidelines were not disseminated to all pharmacy programs and protective measures largely relied on individual pharmacy program. METHODS: A survey was developed by the Committee on Pharmacy Practice Experience Programs in the Korean College of Clinical Pharmacy to document the status of pharmacy programs during the Korea MERS outbreak in 2015. The 10-question survey was distributed to the pharmacy practice experience coordinators to 34 out of 35 pharmacy schools in Korea by emails. RESULTS: Our findings showed that 82.4% of the program coordinators (28/34) responded to the survey, 96.4% of the programs did not have emergency preparedness manuals, administrative meetings were held in 89.3% of the pharmacy programs, the rotation schedules were modified or withheld in 53.6% of schools, and the changes were mostly observed from the programs classified as MERS outbreak regions. CONCLUSION: Further needs in establishing the emergency preparedness manual should be explored for pharmacy education stakeholders.
Subject(s)
Humans , Appointments and Schedules , Civil Defense , Coronavirus Infections , Curriculum , Education , Education, Pharmacy , Electronic Mail , Emergencies , Health Occupations , Korea , Middle East , Nursing , Pharmacy , Schools, Pharmacy , SeoulABSTRACT
OBJECTIVE: Because of communication difficulties, the hearing-impaired face many disadvantages throughout their lives. One of those is limited access to health care services, particularly medication service. Though they suffer from problems related to taking medication properly, there have been few studies on their actual condition of medication use in Korea. This study is to investigate any obstacles to properly taking medications and, therefore, to suggest preliminary evidence for policy measures to improve safe medication use among the hearing-impaired. METHODS: Study participants consisted of hearing-impaired individuals living in Seoul. We also interviewed two sign language interpreters in order to illuminate health care state of the hearing-impaired. In-depth interview for each study participant was recorded and was translated into a written script for analysis. RESULTS: Study participants were comprised of four women (66.6%) and two men (33.3%). There were one participants in 20's, two participants in 30's, one 40's, and two 50's. Sign language interpreters were all women. One was in her 30's and the other was in her 40's. Communication difficulties have been found to be key barrier to use medication safely. A negative image of pharmacists also hinders safe medication usage, lowering access to local pharmacy and leading discretional self-medication. This article provides pharmacists with solutions to promote adherence in this population. CONCLUSION: The hearing-impaired had limited access to medication-related information as well as using services in a hospital and local pharmacy due to their disability. Institutional improvement for safe medication usage among the hearing-impaired is necessary.
Subject(s)
Female , Humans , Male , Delivery of Health Care , Health Services Accessibility , Hearing , Korea , Pharmacists , Pharmacy , Seoul , Sign LanguageABSTRACT
OBJECTIVE: As the demands of pharmacist's role and quality performance have increased, the verification of pharmacist's ability has been required. In this study, we aimed to select appropriate items for assessment of pharmacist's knowledge, attitude and performance. METHODS: Based on the pharmacist job analysis, we selected duties and tasks in consideration of applying pharmacy practical examination through brainstorming of internal researchers and group discussion with experts. Survey was conducted to evaluate the tasks according to the criteria detailed below: Realistic, Understandable, Measurable, Behavioral and Achievable (RUMBA). The subjects included professors at colleges of pharmacy and instructors of institutional or community pharmacy settings. RESULTS: Nine duties including 41 tasks were drawn for the survey through primary internal researchers. Of the 90 respondents, 95.6% were professors or preceptors who was engaged in practical training, and 62.2% had more than five years of practical experience. As a result of survey and discussion with expert panel, selected seven duties were selected as followings: ‘Patient (customer) reception’, ‘Drug preparation and distribution’, ‘Patient care’, ‘Administration’, ‘Patient counseling’, ‘Non-prescription medication counseling’, and ‘Provision of drug information’. The final 20 tasks from seven duties were chosen to assess skills that a pharmacist should be able to perform. CONCLUSION: This is the first study to select the items that can be included in pharmacist practical examination in the future, based on the RUMBA criteria. As a next step, it is necessary to study how to implement these items.
Subject(s)
Humans , Licensure , Pharmacies , Pharmacists , Pharmacy , Surveys and QuestionnairesABSTRACT
OBJECTIVE: The visually impaired have limited access to health care services and related information, and thus, they can have serious hurdles against properly taking medications. Despite that it is important to improve self-care ability of the visually impaired for correct medication use, there have been few studies investigating their needs for health care services in Korea, particularly focusing on proper medication usage. This study is to explore safety-related issues regarding mediation usage among the visually impaired based on in-depth interview. We particularly focus on any obstacles for safe use of medicines including experience on medication-related adverse effects in order to provide preliminary evidence for policy measures to improve proper medication use among the visually impaired. METHODS: Study sample was visually impaired individuals who resided in Seoul area and were registered in the National Association of Visually Impaired. The association helped the process of recruiting the study participants. In-depth interview for each study participants was conducted. Each interview was recorded and later converted into a written script to extract core contents for the analysis. RESULTS: The study participants comprised of three women (42.9%) and four men (57.1%). One was in his 20's, and there were four participants in 30's and two in 40's. Fully impaired participants were majority (5 out of 7). Limitation to physical access to health care providers and health information were the key factors to hamper safe medication utilization among the study participants. Difficulty reading medication information and may take the wrong medication or incorrect doses of medication, resulting in serious consequences, including overdose or inadequate treatment of health problems. Visually impaired patients report increased anxiety related to medication management and must rely on others to obtain necessary drug information. Pharmacists have a unique opportunity to pursue accurate medication adherence in this special population. This article reviews literature illustrating how severe medication mismanagement can occur in the visually impaired elderly and presents resources and solutions for pharmacists to take a larger role in adherence management in this population. CONCLUSION: The visually impaired had difficulties reading medication information and identifying medicines, and took incorrect doses of medications. Public support for safe medication use and medication management among the visually impaired is necessary.
Subject(s)
Aged , Female , Humans , Male , Anxiety , Delivery of Health Care , Health Services Accessibility , Korea , Medication Adherence , Negotiating , Pharmacists , Self Care , SeoulABSTRACT
BACKGROUND: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. METHODS: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product (cCa×P), and the prescription rate of non-calcium based P-binders. RESULTS: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target cCa×P level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher cCa×P levels than 55 mg²/dL² (P <0.001). CONCLUSION: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.
Subject(s)
Humans , Calcium , Chronic Disease , Dialysis , Ethics Committees, Research , Kidney , Miners , Nephrology , Nutritionists , Observational Study , Pharmacists , Prescriptions , Renal Insufficiency, Chronic , Retrospective StudiesABSTRACT
BACKGROUND: The recent change in pharmaceutical education system following the paradigm shift to patient-oriented pharmacy service requires an in-depth discussion to reorganize a future direction and establish a basis for maximizing social values of community pharmacy service. OBJECTIVE: This study was conducted to review the current status of community pharmacy service provision in Korea based on published literatures. METHODS: The electronic databases of National Digital Science Library and Electronic National Assembly Library were used to search the journal articles and dissertation papers. A search term "community pharmacy" was used and the published period was limited to papers published after year 2001, when the legal separation of prescribing and dispensing was implemented. Relevant study reports were also searched manually. Information about pharmacy service provision and study outcomes were retrieved from the selected papers, and classified by predefined individual service scope. RESULTS: A total 33 papers reporting services provided by community pharmacies were selected (journal article 11, dissertation paper 17, and study report 5). Pharmacy services identified in these papers could be classified into prescription dispensing service, pharmaceutical care service, self medication service, other products service, and health promotion service. Twenty papers reported prescription dispensing services, three papers reported pharmaceutical care service, and only two papers reported health promotion service. Current community pharmacy services are highly dependent on prescription drugs while expanded services such as pharmaceutical care and health promotion are peripheral. Most prevalent research topic was medication counseling service (18 papers), reflecting that community pharmacists generally consider it to be the most important and fundamental service. Overall, current pharmacy services are very limited and focus on prescription dispensing service. CONCLUSION: At this point of time requiring expansion and quality improvement of community pharmacy services, we suggest further lively discussion to strengthen pharmacist's functional identity and set conditions for providing socially expected services.
Subject(s)
Humans , Community Pharmacy Services , Counseling , Education, Pharmacy , Health Promotion , Korea , Pharmaceutical Services , Pharmacies , Pharmacists , Prescription Drugs , Prescriptions , Quality Improvement , Self Medication , Social ValuesABSTRACT
We aimed to assess one-year persistence with antihypertensive therapy (AHT) among newly treated uncomplicated hypertensive patients in Korea and to evaluate the effect of initial therapeutic classes on persistence. We retrospectively analyzed a random sample of 20% of newly treated uncomplicated hypertensive patients (n = 45,787) in 2012 from the National Health Insurance claims database. This group was classified into six cohorts based on initial AHT class. We then measured treatment persistence, allowing a prescription gap of 60 days. Adherence to AHT was assessed with the medication possession ratio. Calcium channel blockers (CCB, 43.7%) and angiotensin receptor blockers (ARB, 40.3%) were most commonly prescribed as initial monotherapy. Overall, 62.1% and 42.0% were persistent with any AHT and initial class at one year, respectively, and 64.2% were adherent to antihypertensive treatment. Compared with ARBs, the risk of AHT discontinuation was significantly increased with initial use of thiazide diuretics (hazard ratio [HR], 3.16; 95% confidence interval [CI] 2.96-3.74) and beta blockers (HR, 1.86; CI, 1.77-1.95) and was minimally increased with CCBs (HR, 1.12; CI, 1.08-1.15). In conclusion, persistence and adherence to AHT are suboptimal, but the differences are meaningful in persistence and adherence between initial AHT classes.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adrenergic beta-Antagonists/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/classification , Calcium Channel Blockers/therapeutic use , Cohort Studies , Hypertension/drug therapy , Medication Adherence , Republic of Korea , Retrospective Studies , Sodium Chloride Symporter Inhibitors/therapeutic useABSTRACT
BACKGROUND: Currently, the dosage of tacrolimus used after transplantation is based on the patient's body weight. However, there is a low correlation between body weight and body composition in kidney transplant recipients. In this study, we evaluate the pharmacokinetics of tacrolimus according to body composition in 18 Korean kidney transplant recipients with stable graft function. METHODS: Body composition parameters were calculated using bioelectrical impedance analysis. Pharmacokinetic profiles were determined 0, 1, 2, 3, and 4 hours after treatment with tacrolimus and were compared between high- and low-level median body composition groups. The values of C0, C1, C2, C3, and C4 were used in determining an abbreviated area under the curve (AUC) for tacrolimus. RESULTS: The mean body mass index (BMI) and body composition values were as follows: BMI, 24.3 kg/m2; lean mass, 49.8 kg; and fat mass, 17.4 kg. There were no statistical differences in pharmacokinetic profiles between groups with different BMIs. However, the C0 and C4 in the high-fat group were significantly elevated compared with those of the low-fat group (P=0.024 and 0.031, respectively). Furthermore, the C0, C2, C3, and C4 and the AUC were significantly different between the two lean mass groups (P=0.007, 0.038, 0.047, 0.015, and 0.015, respectively). Other variables, such as waist circumference and arm muscle circumference, did not differentiate between the pharmacokinetic profiles of tacrolimus. CONCLUSION: Taken together, these data suggest that tacrolimus dose monitoring based on body composition may provide adequate dosage leading to favorable long-term outcomes.
Subject(s)
Adipose Tissue , Area Under Curve , Arm , Body Composition , Body Mass Index , Body Weight , Electric Impedance , Kidney , Muscles , Tacrolimus , Transplants , Waist CircumferenceABSTRACT
BACKGROUND: Glutathion S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferase in lung epithelium, plays an important role in cellular protection against oxidative stress and toxic foreign chemicals. GSTP1 (Ile105Val) polymorphism has been reported to be associated with asthma related phenotypes such as atopy and bronchial hyperresponsiveness. Therefore we investigated whether this polymorphism may be associated with the development of aspirin-intolerant asthma (AIA). METHODS: GSTP1 Ile105Val polymorphism was determined using a single based extension method in 88 AIA subjects and compared to 154 aspirin-tolerant asthma (ATA) subjects and 119 normal healthy controls (NC) recruited from the Korean population. RESULTS: No significant differences in allele and genotype frequencies of the GSTP1 Ilel105Val polymorphism were observed in the three groups (p> 0.05). However, minor G allele frequency of the GSTP1 Ilel105Val polymorphism in AIA group (16.5%) tended to be lower than in the NC group (20.6%). CONCLUSION: These results suggest a lack of association of the GSTPI Ilel105Val gene polymorphism with AIA phenotype in the Korean population [word count: 159].
Subject(s)
Male , Humans , Female , Adult , Polymorphism, Restriction Fragment Length , Polymorphism, Genetic , Korea , Isoenzymes/genetics , Glutathione S-Transferase pi/genetics , Glutathione/metabolism , Genotype , Case-Control Studies , Asthma/chemically induced , Aspirin/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , AllelesABSTRACT
Intercellular adhesion molecule-1 (ICAM-1) is a membrane protein, exists as a dimer on the cell surface, and interacts with leukocyte function associated antigen-1 (LFA-1), a member of beta2-integrin family. A soluble circulating form of ICAM-1 (sICAM-1) is also detected in human serum, and has been implicated as a regulator for LFA-1-dependent cell-cell interaction in vivo. However, previous reports demonstrated that sICAM-1 shows little inhibitory effect on LFA-1 binding to ICAM-l, indicating that sICAM-1 is unlikely to antagonize LFA-1/ICAM-1-mediated cellular events in vivo. Here, we investigated the property of the dimeric sICAM-1 as an inhibitor of LFA-1 interaction with ICAM-3, since the lower avidity of LFA-1 for ICAM-3 compared with ICAM-1 or ICAM-2 had been speculated. Using recently constructed heterodimeric sICAM-1 joined at the C terminus via an a-helical coiled coil (ACID-BASE) (Jun, CD. et al., 2001, Proc Natl Acad Sci 98, 6830-6835), we also tested whether the structural integrity in dimer could affect the inhibitory action of sICAM-1. Engineered sICAM-1 dimer that contained intact ectodomain (E34/E34) significantly blocked SKW3 cell (LFA-1+) binding to ICAM-3, but not to ICAM-1 and ICAM-2, indicating the lower avidity of LFA-1 to ICAM-3 than that of both ICAM-1 and ICAM-2. A one binding site knock out mutant (E34/K34) showed -2-fold reduction in efficiency compared with E34/E34 to inhibit cell binding. Interestingly, a one binding domain deletion mutant (E34/deltaD1-D2) showed significant reduction (~5-fold) compare with E34/K34, suggesting that structural integrity, which is precluded in E34/deltaD1-D2, is necessary for optimal binding of dimeric sICAM-1 to LFA-1, thereby inhibiting LFA-1/ICAM-3-dependent adhesion. Furthermore, BIAcore affinity measurements revealed that E34/deltaD1-D2 bound to immobilized soluble open LFA-1 I domain with an -3-fold reduced affinity compared with E34/K34. Overall, our results demonstrate that maintaining the structural integrity in dimer is necessary for optimal binding of sICAM-1 to LFA-1, and further suggest the therapeutic potential of dimeric sICAM-1 to antagonize LFA-1/ICAM-3-mediated cellular events in vivo.
Subject(s)
Humans , Binding Sites , Intercellular Adhesion Molecule-1 , Leukocytes , Lymphocyte Function-Associated Antigen-1 , Membrane ProteinsABSTRACT
PURPOSE: Mycophenolate mofetil (MMF) given orally as 1000 mg twice daily has shown to be effective in the suppression of acute allograft rejection following renal transplantation. However, Korean transplant patients are usually administered with a lower dose of MMF (1~1.5 gm/day) than the recommended dose due to high incidence of gastrointestinal intolerance. The purpose of this study was to characterize the pharmacokinetic parameters of the mycophenolic acid (MPA), the active form of MMF, in Korean kidney transplant recipients. METHODS: The plasma MPA concentrations of 10 Korean kidney transplant recipients (7 men and 3 women) administered with a suboptimal dose of MMF (750 mg twice a day) were measured at 2 weeks of the MMF therapy by HPLC method. RESULTS: Plasma MPA concentration-time curve pattern of patients taking lower doses of MPA was consistent with previously reported profiles of patients taking the fully recommended doses. The plasma MPA concentration-time curve was characterized by an early sharp peak within 1 hour and a small second peak in some patients at 4~12 hours postdose. The mean ( SD) Cmax was 8.73 4.65micro gram/ml, and the mean MPA AUC was calculated as 18.45 4.25micro gram hr/ml. The mean fraction of free MPA, which is pharmacologically active, was 1.60 0.23% and this value seemed similar to previously reported data. The patient's age, weight, body surface area, and renal function did not influence the MPA AUC. However, a difference in AUC according to sex was statistically significant (P=0.0227). Free fraction of MPA appeared not to be affected by serum albumin and renal function when creatinine clearance was above 40 ml/min. Correlation analysis between each plasma concentration and AUC for the limited strategy of MMF therapeutic drug monitoring (TDM) resulted that the concentrations of predose, 1 hr post-dose, and 8 hr post-dose were positively related with AUC value, and their coefficients of correlation were 0.74545 (P=0.0133), 0.68485 (P=0.0289), and 0.63636 (P=0.0479), respectively. CONCLUSION: This study have shown that the pattern of the time-concentration profile of MPA was similar to the results of other studies performed with Caucasians, although there was interindividual variability of MPA AUC, Cmax, and Tmax.