• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.227-239
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• 2023

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.

• Journal of Life Science
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• v.33 no.9
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• pp.754-765
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• 2023

Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.

• The Journal of KAIRB
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• v.5 no.1
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• pp.14-20
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• 2023

Purpose: To obtain fundamental data on selection tools for an internal audit and develop a new guideline. We scored the indicated points from the internal audit, identified the research progress and problems that occurred, and confirmed the validity of the risk factors involved. Methods: Of the 63 internal audits conducted by Keimyung University Dongsan Hospital from 2014 to 2021, we analyzed 55 clinical trials with an inspection checklist. We excluded 8 that failed to transfer data and refused to comply with the internal audit. The statistical summary of the collected data was verified and interpreted by using frequency analysis and a chi-square test. Result: Of total 55 cases included in the internal audit, sponsor-initiated trial (SIT) was 63.6% (vs. investigator-initiated trial [IIT]), clinical trial for investigational drug was 71.0% (vs. nonclinical or clinical trial for investigational device), domestic multicenter trial was 60.0% (vs. single center or multinational multicenter trial), and trial requisition for MFDS approval was 69.1% (vs. exception for MFDS approval). The 10 areas of the clinical trial inspection checklist (reports, protection of subjects, compliance with protocols, records, management of investigational drug and/or device, delegation of duties, qualification of investigators, management of specimen, contract-agreement and approval of protocols, and preservation of recorded documents) were weighted between 2 to 5 points. The average of the total points was 16.09±13.2 and 20 clinical trials were above the average. As a result of comparing the average of the total points weighted by year, the highest score was in 2020. The 4 factors that play significant roles in determining the internal quality were (1) principal subjects that initiated the clinical trials (p=0.049), (2) type (p=0.003), (3) phase of clinical trials (p=0.024), and (4) number of registered subjects reported at the time of continuing deliberation (p=0.019). Of the 10 areas of the clinical trial inspection checklist, 'record' was the most inappropriate and insufficient. We found more indicated points; the quality of performance declined in IIT, nonclinical trials, and other clinical trials that were not in phase I1-IV4, and the study of more than 30 registered subjects at the time of continuing review. Conclusion: If an institution has an internal audit selection tool that reflects the aforementioned risk factors, it will be possible to effectively manage high-risk studies; thereby, contributing to an efficient internal audit and improving the quality of clinical trials.

• Journal of Preventive Medicine and Public Health
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• v.23 no.4 s.32
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• pp.416-427
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• 1990

Unfortunately, we have poor knowledge of medical technology in North Korea. This study has thus attempted to identify the level and status of medical technology development through analyzing the contents of medical textbooks currently in use. This study has assumed that three factors are influencing the level and status of medical technology in a society ; the level of socio-economic development in general, the level of scientific technology revolution and health policy. Forty textbooks are collected for this purpose. The main findings are summarized as follows : 1) North Korea s strengths in that (1) its herb drugs, which are in a broad use, are cheaper, more safe and more attainable than bio-equivalent chemical ones, and (2) the development of its medical technology was carried out with emphasis on the practical and basic health needs. 2) North Korea has weaknesses in that (1) its medical diagnostic method largely depends on manual procedures, (2) the R & D investment in the development of chemical drugs, especially antibiotics, is very small, (3) the amount of medical equipments is in a absolute shortage, and (4) the medical technology is destitute of specialty, caused mainly by the overemphasis on Juche-Uihak or herb medicine. 3) Medical technology has two faces, positive and negative so that it cannot be successfully evaluated by one. It eventually acts a positive function for public health through developments of drug, equipment and new medical treatment method. But it is also true that it has negative effects such as the dehumanization of high cost medical technology, cost hike due to over-investments in expensive equipment and the absence of wholistic care from overspecialization. 4) We have to consider economic status and the social needs of medical care in order to evaluate the medical technology of a society. It is also the case with North Korea. A whole picture of the North Korean medical technology could be understood only if further comprehensive studies of medical technology are to be carried out for North Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6117-6121
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• 2015

Background: Most northeast Thai vegetables may play roles in human health by acting as antioxidant and anticancer agents. Recent study showed that Cratoxylum formosum subsp. pruniflorum (Kurz.) Gogel. (Teawdang) could inhibit growth of liver cancer cell lines. Cervical cancer, which has human papilloma virus as its main cause, is found at high incidence in Thailand. Due to increasing drug resistance, searches for potential anticancer compounds from natural source are required. Therefore, our purpose was to evaluate the cytotoxicity of Teawdang extracts in cervical cancer cell lines. Materials and Methods: Teawdang edible parts, purchased from Khon Kaen market during July-October 2013 was extracted with organic solvent. Phenolic profiles of crude hexane (CHE), ethyl acetate (CEE), methanol (CME) and water (CWE) extracts were performed by high performance liquid chromatographic (HPLC) techniques. Their cytotoxic effects on cervical cancer cells were investigated with HPV-non infected (C-33A) and HPV-infected (HeLa and SiHa) cell lines. Results: HPLC profiles showed that all crude extracts contained caffeine, ferulic acid and resveratrol. CME and CEE had high contents of gallic acid and quercetin. Catechin was found only in CWE. Cytotoxicity test showed that CEE had the lowest IC50 on HeLa ($143.18{\pm}13.35 {\mu}g/mL$) and SiHa cells ($106.45{\pm}15.73{\mu}g/mL$). C-33A cells were inhibited by CWE ($IC50=130.95{\pm}3.83{\mu}g/mL$). Conclusions: There were several phenolic compounds in Teawdang extracts which may have cytotoxic effects on cervical cancer cell lines. Investigation of these bioactive compounds as new sources of anticancer agents is recommended.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.5
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• pp.569-577
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• 2007

The purpose of the present study was to propose some amendments on nutrient standard regulations of infant formula in Korea. For this purpose, we compared and analyzed the nutrient regulations of Korea, CODEX, U.S.A, Japan, EU, Australia and New Zealand. Some developing aspects of Korea's nutrient standard regulations for infant formula need to be examined as follows: firstly, both milk-based formula and soy-based formula standards would be unified into an infant formula, and the user of infant formula would be categorized for babies less than 6 month old. Secondly, nitrogen conversion factor of milk protein in the infant formula would be 6.38, which is the same as that of CODEX Revised Standard. Protein quantities could be differentiated by protein sources, and essential amino acids in human milk would be standardized according to protein contents. Thirdly, $\alpha$-linolenic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) as essential fatty acids and trans fatty acid would be standardized in terms of the contents. Fourthly, it is recommended that the unit of vitamins and minerals would be changed from g/100 g to g/100 kcal, and individual vitamins and mineral would have their maximum values. Finally, 5 nucleotides (cytidine, uridine, adenosine, guanosine, inosine 5'-monophosphate) and fluoride would be required for the strengthening the immunity and the development of teeth, respectively. In conclusion, the scientific studies on amendment scheme of nutrient standard regulations of infant formula is very important to fortify nutritional completeness for Korean infants and young children.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.471-478
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• 2000

The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

• Analytical Science and Technology
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• v.25 no.4
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• pp.250-256
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• 2012

Two marker compounds of Achyranthis Radix, ecdysterone and inokosterone, were analyzed by HPLC on an ODS column ($250{\times}4.6$ mm, 5 ${\mu}m$) with a mobile phase of 15% acetonitrile containing 0.08% formic acid at a flow rate of 1.0 mL/min and a detection wavelength of UV 254 nm. The method was validated by ICH guideline and applied to the monitoring of marker compounds in 93 samples of Achyranthis Radix collected at various areas in Korea and China. The new content criteria of ecdysterone and inokosterone, established using linear regression method were 0.033% and 0.020%, respectively. When the new content criteria were applied to the quality control test of commercial Achyranthis Radix, 95.4% of total samples including 100% of Korean and 92.6% of Chinese samples were passed the test. Application of new content criteria could protect the Korean products and decrease the distribution of Chinese products with lower quality.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.93-102
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• 1996

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as nephrotoxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and broadening the clinical spectrum of activity of cisplatin. We synthesized new Pt(II) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,3-bis(diphenyl phosphino)propane (DPPP) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of PC-1 [Pt(cis-dach) (DPPP)]. $2NO_3_2$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC-1 was demonstrated acceptable antitumor activity aganist SKOV -3, OVCAR-3 human ovarian adenocarcinomacells and significant activity as compared with that of cisplatin. The toxicity of PC-1 was found quite less than that of cisplatin using MTT, $[^3H]thymidine$ uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.