• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.45-55
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• 1983

A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

• Korean Chemical Engineering Research
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• v.58 no.4
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• pp.541-549
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• 2020

The Drug Delivery System (DDS) is defined as a technology for designing existing or new drug formulations and optimizing drug treatment. DDS is designed to efficiently deliver drugs for the care of diseases, minimize the side effects of drug, and maximize drug efficacy. In this study, the optimization of tripolyphosphate (TPP) concentration on the size of Chitosan nanoparticles (CNPs) produced by crosslinking with chitosan was measured. In addition, the characteristics of Fe₃O₄-CNPs according to the amount of iron oxide (Fe₃O₄) were measured, and it was confirmed that the higher the amount of Fe₃O₄, the better the characteristics as a magnetic drug carrier were displayed. Through the ninhydrin reaction, a calibration curve was obtained according to the concentration of γ-aminobutyric acid (GABA) of Y = 0.00373exp(179.729X)-0.0114 (R² = 0.989) in the low concentration (0.004 to 0.02 wt%) and Y = 21.680X-0.290 (R² = 0.999) in the high concentration (0.02 to 0.1 wt%). Absorption was constant at about 62.5% above 0.04 g of initial GABA. In addition, the amount of GABA released from GABA-Fe₃O₄-CNPs over time was measured to confirm that drug release was terminated after about 24 hr. Finally, GABA-Fe₃O₄-CNPs performed under the optimal conditions were spherical particles of about 150 nm, and it was confirmed that the properties of the particles appear well, indicating that GABA-Fe₃O₄-CNPs were suitable as drug carriers.

• Clinical and Experimental Pediatrics
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• v.49 no.8
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• pp.845-850
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• 2006

Purpose : To assess the incidence of neonatal hearing loss in a neonatal intensive care unit and the relative importance of risk factors for hearing imparement in a neonatal intensive care unit which the Joint Committee on Infant Hearing(JCIH) had recommended. Methods : One thousand, two hundred and one newborns admitted to the Good Moonhwa Intensive Care Unit from May 2003 to December 2005 were assesed using the automated auditory brainstem response(AABR). The screening was performed on those aged more than 36 weeks and weighing more than 2,200 g. We divided the infants into two groups, 'pass' and 'refer'. The 'refer' group were retested one month later, and if classified as 'refer' during the retest, were referred to a hearing impairment clinic. Results : From the 1,201 neonates, 1,187(98.8 percent) passed the test and 14(1.2 percent) failed. 293(24.4 percent) of the 1,201 neonates had a risk factor for hearing impairment; 282(96.2 percent) passed the test and 11(3.8 percent) failed. The group with risk factors were shown to have a higher incidence of hearing loss(P<0.001). The neonates in the refer group were shown to have a higher incidence of ototoxic drugs(P<0.001), low birth weight(<1,500 g)(P<0.001) and craniofacial anomalies(P=0.007). On the other hand, there were no statistical differences between the pass and refer groups in congenital infection, hyperbilirubinemia, bacterial meningitis, low Apgar scores, prolonged mechanical ventilation and syndromes known to include hearing loss. Conclusion : In order to identify hearing-impaired infants within an appropriate period, neonatal hearing screening tests and identification of the risk factors for neonatal hearing loss are important.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.157-165
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• 2003

Purpose : $Henoch-Sch\"{o}nlein$ purpura(HSP) is a systemic vasculitis that involves multiple organs, especially the kidney, which is the most important organ in determining the prognosis of the disease. The morbidity of HSP nephritis in adults is low and there have been little research done on its clinical course so far. Therefore, we have compared the clinical course of HSP nephritis in children and adults in Korea. Methods : We retrospectively analyzed 81 cases of HSP nephritis in children younger than 15 years of age, and 25 cases of adults older than 15 years of age who were admitted to Yonsei University Medical College Severance Hospital from Jan. 1986 to May 2003. Results : The male to female ratio was 1.5 : 1 in children and 1.3 : 1 in adults. The incidence of HSP nephritis for both age groups was found to be increased during the autumn and winter. Infection was the predisposing factor in 39 cases(48.1%) of children, 16 cases(64.0%) of adults, and drugs were the predisposing factor in 8 cases(9.9%) of children and 4 cases (16.0%) of adults. All patients initially presented with microscopic hematuria. Thirteen cases (16.0%) of children and 7 cases(28.0%) of adults initially showed proteinuria of nephrotic range. Thirty four cases(42.0%) of children and 4 cases(16.0%) of adults showed normal urinalysis after treatment. Asymptomatic urinary abnormalities were found in 41 cases(50.6%) of children and 18 cases(72.0%) of adults. Complications such as nephrotic syndrome and hypertension were found in 3 cases(3.7%) of children and 2 cases(8.0%) of adults. Three children(3.7%) and 1(4.0%) adult required dialysis or renal transplantation. Follow-up renal biopsies were performed on 21 children, of whom 10 cases(47.6%) did not show any histologic change, 9 cases(42.9%) showed low grade changes, and 2 cases(9.5%) showed high grade changes. Prognosis was gloomy when proteinuria of nephrotic range and high grade of abnormal histology were present at diagnosis, and there was no significant difference between the two groups(P<0.05) Conclusion : This study showed that there was no difference in terms of the clinical features and courses between the children and adults with HSP nephritis. Proteinuria of nephrotic range and the severity of abnormal histologic changes at diagnosis were found to be associated with a bad prognosis, therefore we recommend that patients with these features require long term follow-up and management.

• Journal of Yeungnam Medical Science
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• v.4 no.2
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• pp.113-120
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• 1987

The effect of intravesical formalin instillation as a therapeutic modality for intractable bladder hemorrhage is well known. And despite clear evidence of therapeutic efficacy of intravesical cytotoxic drugs and/or BCG immunotherapy, there have been substantial recurrences during followup after transurethral resection for superficial bladder tumor. If formalin injected at the bed of superficial bladder tumor is able to coagulate and necrotize the tumor, it will be greatly helpful to the patients With recurrent bladder tumor developed during followup. Since this technique is applicable on outpatient basis, an economical as well as a psychological burden of the patients can be reduced considerably. The purpose of this study is to evaluate the effect of submucosal formalin injection on rat bladder wall, 36 healthy adult male Sprague-Dawley rats (weighing 350gm in average) were divided into 3 groups: In Group I (control group), 0.01ml of normal saline was injected submucosally at the left posterolateral wall of the bladder opened under intraperitoneal Nembutal anesthesia ; In Group II and III, 0.01 ml of 10% and 4% formalin, respectively, were administered at the same site as in the Group I, two rats in each group were sacrificed at day 1, 2, and 3, and week 1, 2 and 4 after injection, respectively. Gross and microscopic examination of the cystectomized specimen were done in each group. In the Group II, bladder stones were formed at week I, and in both the Group I and III, stones were seen at week 2 post injection. There was no significant difference III histologic findings of the bladder between the group II and III. Mucosal ulcer and/or prominent mucosal disruption was observed at 24 hours after injection in both Group II and III. Epithelial regeneration began at day 2, and was marked at day 3, and epithelial lining was almost normalized one week after injection. Subepithelial edema, telangiectasia and inflammatory reaction were prominent at 24 hours post formalin injection. Subepithelial edema persisted in moderate degree for 1 week. Telangiectasia and inflammatory reaction were noted for 4 weeks. Mild degree of these findings also appeared In the control group. Fibroblastic proliferation appeared at day 2 and persisted in moderate degree for 4 weeks. There has been no mortality or bladder perforation. These results suggest that clinical application of this technique is feasible for the selected cases of recurrent, solitary superficial bladder tumor. However, optimal dosage of formalin in relation to the size of the lesion remains to be investigated.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.111-121
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• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.12 no.1
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• pp.138-148
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• 2001

The focus of the research was on identifying the risk factors that may result in unprepared intercourse among the adolescent from an ecological systems prospective. A survey questionnaire was conducted from September through December 1999 to 2326 youths, ages from 13-18 years old. After eliminating thirty respondents from Unwed Mother's Home we found that 8.8% of the remaining respondents had experienced sexual intercourse. Of those, 5% of the female and 13.4% of male adolescents has had sexual intercourse, showing 2.7 times more for the male sample population. Broken down to age groups, 3.2% of the thirteen years old group and 19.2% of the eighteen years old group had experienced intercourse, an almost six fold increase in the older age group. To find out the differences between those who had and not had experienced intercourse the group was then divided into two comparative groups by same sex and age variables. Findings from comparative analysis identified five ecological system risk factors among the youth sample that had intercourse；First, individual factor：adolescents who thought less of themselves or didn't consider their potentials, those more exposed other risk behaviors such as drinking, smoking, drugs, runaway and come in contact with pornography, those who thought they knew more about sex and etc. Second, family factor：those who thought family was less important, had less supportive family, higher or lower income family and etc. Third, peer factor：Both groups thought friends were important and had their support. The group with intercourse experience seems to be think that more peers are experiencing other risk behavior. Fourth, school factor：Those in the group who had experienced intercourse seems to think school is less important and with lower academic achievements. Fifth, community factor：There were no statistical significant differences found between the two groups. The overall results from this study implies that if we want to prevent our youths from having unprepared intercourse during adolescence the significance of having meaningful emerging self, family relationship and school experience is important. This study identified the risk factors leading to adolescent sexual intercourse but further research is necessary in finding out about their predictability.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.786-792
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• 1997

A clinical study of 71 cases of pulmonary tuberculosis that had had surgical resection during the period of 7 years and 6months from January 1989 to June 1996 in National Masan Tuberculosis Hospital. The results were as follows. 1. The ratio of male to female was 3.7:1 and in the age incidence the fourth decade was 22%, the third decade 15%. Although medical treatment was performed for more than 3 to 6 months, preoHeratively the conversion failure rate of positive sputum to negative state was 66.2%(47 cases). Of the failure cases, multiple-drug-resistant(MDR) patients were 41 cases(87.2%), 3. In MDR group, preoperatively conversion failure rate was 71.9%. 4. From the view of indica ion for lung resection on the radiographic finding, cavitary lesions were 43 cases(60.6%), destroyed lung lesions were 24 cases(33.8%). 5. The incidence of postoperative complication was 28.2%(20 cases). All cases were MDR 6. group and the most common of complication was tuberculosis spreading. In bilateral lesion, incidence of postoperative tuberculosis spreading was 25%(7 cases). Of the 7 cases, there was the cavitary lesion in 6 cases(86.7%). Total conversion rate of AFB positive sputum to negative state related to resectional sugery was 76.6% and in MDR group conversion rate of AFB positive sputum to negative state was 73.2% Conversion rate of MDR group with bilateral lesion was the lowest(60%). Conversion rate of drug-sensitivity group was 100% regardeless of lesions Slt to. In conclusion, despite of long-standing medical treatment, it is difficult to converse sputum-positive to negative state in multiple-drug resistance patients and that increases postoperative complications su h as tuberculosis relapse as a lack of appropriate drugs postoperatively. Postoperative conversion rate of sputum-positive to negative state was decreased in multiple-drug resistance patients. Because multiple-drug resistance patients have inireased due to several factors in Korea, it is important to prevent spreading of multiple-drug resistnce patients through the aggressive operative treatment. When the first medical therapy is fail or drug-resistance is found, operative treatment should be considered with the secondary medical therapy. The operation should be aggressively attempted even though at first medical treatment if indicated.