OBJECTIVES: Treating olfactory dysfunction is a challenge for physicians. One of the therapeutic options could be transplantation of stem cells. In this study, neural stem cells were transplanted into anosmic mice. METHODS: Neural stem cells were generated from the olfactory bulb of green fluorescent protein (GFP)-transgenic C57BL6 mice. Anosmia were induced by injection of intraperitoneal 3-methylindole. The neural stem cells were transplanted transnasally on the next day. The olfactory function was evaluated by a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis at 4 weeks. RESULTS: Twenty-five percent (6/24) of the control mice that were not transplanted with neural stem cells survived at 4 weeks while 67% (8/12) of the transplanted mice survived (P=0.029). The food finding test showed that the transplanted mice resumed finding food at 3 weeks while the control mice resumed finding food at 4 weeks. GFP-positive cells were observed in the olfactory neuroepithelium of the transplanted mice. Western blotting revealed that the olfactory marker protein expression was significantly lower in the control mice than that in the transplanted mice. CONCLUSION: This study demonstrated that improvement of mouse survival was achieved and recovery of olfactory function was promoted by transnasal transplantation of neural stem cells in the anosmic mouse model. These results indicate that stem cells might be one of the future modalities for treating olfactory impairment.
Animals ; Blotting, Western ; Mice ; Neural Stem Cells ; Olfaction Disorders ; Olfactory Bulb ; Olfactory Marker Protein ; Skatole ; Smell ; Stem Cells ; Transplants

BACKGROUND: C677T single nucleotide polymorphism (SNP) of Methylentetrahydrofolate reductase (MTHFR) has been known to be associated with plasma homocysteine (Hcy) levels, which is an independent risk factor for stroke. However, recent large clinical trials did not show any benefits of Hcy lowering therapy with vitamins on the prevention of stroke. We hypothesized that the Hcy lowering effect by vitamins would be different according to the MTHFR C677T SNP types (CC, CT or TT), which may influence the benefits of vitamins by Hcy lowering on stroke prevention. METHODS: The authors retrospectively studied acute stroke patients with information of the genotype of MTHFR and serial levels of Hcy during a recent 4 year period (July 2002 - Dec 2005). Vitamins (folic acid 1 mg, and/or cobalamin 750 microgram and pyridoxine 75 mg) were prescribed to the patients whose basal plasma Hcy levels were above 12 umol/L. RESULTS: Among 172 patients, 68 patients took vitamins. The mean basal Hcy level was significantly higher in the TT type than the others, and was decreased by vitamin therapy. Distribution of homocysteine grading (normal, intermediate or high) in follow up was not significantly different according to these SNP types. CONCLUSIONS: The Hcy lowering effect by vitamins was not different by MTHFR genetic polymorphism. Considering the higher prevalence of certain gene types in stroke and our study results, genetic factors such as MTHFR polymorphism may play an important role on the development of stroke rather than the plasma Hcy levels.
Follow-Up Studies ; Genotype ; Homocysteine* ; Humans ; Oxidoreductases ; Plasma* ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide* ; Prevalence ; Pyridoxine ; Retrospective Studies ; Risk Factors ; Stroke* ; Vitamin B 12 ; Vitamins*

In 2016, the clinical chemistry proficiency-testing program consisted of 21 programs, including the general chemistry program of the Korean Association of External Quality Assessment Service. The general chemistry program consisted of 28 test items and was conducted using two level control materials four times per year. Based on the information and results for each test item entered by each institution, statistical analysis data according to test method, instrument, and reagent were reported. The report comprised a general statistics report showing the characteristics of all participating institutions and a separate institutional report showing the evaluation data of individual institutions. The statistics included the number of participating institutions and the mean, standard deviation, coefficient of variation, median, minimum, and maximum values for each group. Each report was composed of a table, histogram, and Levey-Jennings chart showing the statistics for each test item. The results of each institution and the statistics for each classification are presented in the table showing the statistics, and a standard deviation index is presented together with a method classification and a classification by reagent companies. A total of 14 items, including albumin, were evaluated by more than 1,000 institutions. There was no significant difference in the distribution of the measurement methods compared with those used in the previous year. The coefficient of variation showed a tendency to increase as the concentration of the level control material decreased and as the number of participating institutions decreased for each test item. Most of them showed a coefficient of variation within 10%. These statistical data will be useful when interpreting the survey results from the institutions and selecting a test method.
Chemistry ; Chemistry, Clinical* ; Classification ; Korea* ; Methods

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.
China ; Developed Countries ; Sample Size ; Social Control, Formal* ; United States Food and Drug Administration

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.

BACKGROUND: Once the diagnosis of operable breast cancer has been made, the single most predictive factor is lymph node status. Although patients with lymph node initially reported as histologically negative have a relatively good prognosis, the relapse rate is still considerable. In an effort to detect micrometastases in the axillary nodes, various antibodies have been used that recognize membrane and cytokeratin antigens. Cytokeratin antigens are expressed by epithelial tumors and are not expressed by normal lymphoid tissues. This study uses an immunohistochemical method to examine the incidence and the prognostic significance of such micrometastases in a series of patients with "node-negative" breast cancer. METHODS: The study population consisted of a retrospective series of 150 patient who were treated at Soonchunhyang University Hospital for breast cancer between March 1992 and February 1998. Based on the original pathologic examination, patients had negative axillary nodes. Pan-cytokeratin, a cocktail of monoclonal antibodies to cytokeratin (58 kd, 56 kd, 52 kd, 45 kd), and the avidin-biotin-peroxidase- complex technique were used to detect micrometastases in paraffin embedded lymph nodes. RESULTS: Micrometastases were detected in 16 (10.7%) patients. The recurrence rate for patients with micrometastases was 6.3% (1/16), and the recurrence rate for patients without micrometastases was 1.5% (2/134). Micrometastases correlated with the histological type (P=0.026) and were seen more frequently with larger tumor size, higher anaplastic nuclear grade, and overexpression of p53.
Antibodies ; Antibodies, Monoclonal ; Breast Neoplasms* ; Breast* ; Diagnosis ; Fibrinogen ; Humans ; Incidence ; Keratins ; Lymph Nodes* ; Lymphoid Tissue ; Membranes ; Neoplasm Micrometastasis* ; Paraffin ; Prognosis ; Recurrence ; Retrospective Studies