• Applied Microscopy
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• v.39 no.3
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• pp.205-218
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• 2009

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group and BCG-treated group). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of 0.7 ${\mu}Ci/g$ of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in a dark room. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. On the light microscopic study, gastric mucosae had no morphological changes following the injection of BCG. On the electron microscopic study, in the BCG-treated mice, myelin figures and multivesicular bodies within the gastric epithelial cells were observed more frequently than in those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 380.2 (${\pm}31.35$), 426.1 (${\pm}28.43$) and 301.8 (${\pm}34.63$), respectively. In the BCG-treated mice, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control and tumor control ones. From the above results, BCG may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric epithelial cells. These results suggest that BCG is expected as one of the effective supplemental anticancer drugs.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.215-227
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• 2018

Purpose: This study was conducted to verify the effects of increases in consuming Korean food in patients who underwent cardiovascular disease (CVD) surgery based on a Korean diet control education program and to investigate the effects of Korean diet control nutrition education on risk factors of CVD, changes in amounts of medication, and nutritional intakes. Methods: The subjects consisted of 15 patients who have undergone CVD surgery within three years and continuously taken cardiovascular drugs. The Korean traditional diet (KTD) emphasizes intake of vegetables and fermented foods to lower saturated fat and cholesterol intake. We applied a KTD education program that included a modified DASH (The dietary approaches to stop hypertension) diet for cardiovascular disease patients. Korean diet control education was then applied to the patients for 12 weeks to evaluate the risk factors of CVD and the state of nutritional intakes. Results: The Korean diet control compliance score increased significantly (p < 0.001) as Korean diet control education was implemented. Additionally, the obesity indexes, waist circumference (WC) (p = 0.002) and waist-to-hip ratio (WHR) decreased significantly (p < 0.001) after subjects received the education. Moreover, the glycemic control index, HbA1c, was significantly decreased (p < 0.05) from $7.3{\pm}1.0%$ before the education to $7.0{\pm}1.1%$ after the education. Changes in the amounts of Korean diet intake consisted of significant increases in cooked rice with whole grains, narmuls (vegetables either raw or cooked), kimchi, and traditional fermented foods following the education. Moreover, the nutritional intake after the education showed significant decreases (p < 0.05) in animal protein, animal lipids, and cholesterol. However, the intakes of Na, K, dietary fiber, vitamin A, vitamin $B_6$, vitamin C, and folic acid were significantly increased. Conclusion: The active encouragement of consuming Korean food and the intervention of implementing diet control education positively affected nutritional intake, the obesity index and glycemic control of patients who have undergone CVD surgery.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.228-241
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• 2018

Purpose: The health risk of women increases after menopause. This study evaluated the effectiveness of a public health center-based nutrition education program for hypertension in women older than 50 years of age. Methods: The program included 8-week nutrition education and 8-week follow-up with keeping a health diary and nutrition counseling. The program was evaluated three times: before and after the nutrition education, and after the follow-up. The subjects were classified into hypertensives (n = 44) or normotensives (n = 71). Results: The rate of taking antihypertensive drugs in the hypertensive group was 86.4%. The systolic blood pressure decreased in the hypertensive and normotensive groups after nutrition education (p < 0.05). The body weight (p < 0.001), BMI (p < 0.001), waist circumference (p < 0.001), and percent body fat (p < 0.01) were also decreased after nutrition education in both groups. The hypertensive group showed an increase in HDL-cholesterol level (p < 0.001) and decreases in triglycerides (p < 0.01) and LDL-cholesterol (p < 0.05) levels after completion of the program. The normotensive group also displayed significant changes in HDL-cholesterol (p < 0.001) and triglycerides (p < 0.01). The dietary habits and nutrition knowledge on sodium and hypertension were improved in both groups (p < 0.001). The total score of dietary behavior related to the sodium intake was improved in the normotensive group (p < 0.001). The total score of the high sodium dish frequency questionnaire decreased in both groups after nutrition education and completion of the program compared to that before the program. Decreases in the consumption frequencies of noodles, pot stews and stews, Kimchi, and beverages were significant. The total self-efficacy score was increased in both groups by the program (p < 0.001). In particular, the hypertensive group showed improvement in all items. Conclusion: This public health center-based nutrition education program may contribute to the prevention and management of hypertension and chronic diseases in women over 50 years of age.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.14 no.1
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• pp.19-42
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• 2008

Blood-Letting Therapy is a rational and ecological medical treatment by which we can heal most of the diseases by removing the static blood which precipitates in the blood vessel and blocks the flowing of blood. And the static blood is the generic term for the injurious, bad, dead and precipitated blood which is blocked the capillary vessel. The Yellow Emperor's Canon of Internal Medicine says that "the patient is treated with drugs internally and stone acupuncture externally. "In the old texts, the blood-letting therapy is mentioned as blood-letting, network vessel pricking, bloodletting, pricking, and arousing pulses etc and it is noted down as the method of network vessel pricking in 'On the Application of Needles' of Spiritual Pivot. Nine-pricking therapy, twelve-pricking therapy and five-pricking therapy are recorded in the methods of network vessel pricking and among them, the method of squeezing blood after pricking the affected part is explained as the network vessel pricking. There are four methods of network vessel pricking, pricking, picking, cluster needling and scatter-pricking and they are fluidly applied to the various symptoms of diseases. In 'On Discriminative Treating for Patients of Different Regions' in Elementary Questions, Ki-baek emphasizes "most of the local people, there are black in skin and loose in striate, and their diseases are mostly of carbuncle kind. It is suitable to treat the disease with stone therapy to prick with stone, so the stone therapy is transmitted from the east. "And in 'On the Corresponding Relation Between the Eum and Yang of Man and All Things' in Elementary Questions, when the Emperor asked Ki-Back, he answered "sthenia means the sthenia of evil, and deficiency means the deficiency of healthy energy. When the blood is sthenic, the evil should be discharged by pricking when out letting the blood; deficiency of vital energy is the asthenia of channels and network vessels, so the energy should drain from the channel which is not deficient, to replenish. "And in this case we can use the methods of 'Breaking out the static bloods', 'driving out the static bloods', blood-letting'. With this we can infer that the blood-letting therapy is made use of the important medical treatments from the ancient times. Especially in referring to the principles of treatment in The Yellow Emperor's Canon of Internal Medicine, it mostly alluded to acupuncture therapies and only eleven times to medicinal treatments. This is to verify that the blood-letting therapy formed the foundation of the medical art. In Dong's Therapy of Acupuncture-Moxibustion and Bloodletting, Dong Kyeong-Chang gave emphasis on the points that there must be extravasated bloods without exception in the serious illnesses which is old, unnatural, accompanying acute pains and so we can revive our body‘s sprit by circulating 'gi' and static blood piled up in the network vessel, regulating the weakness and strength, and controling the disharmony of the internal organs. The blood-letting therapy has effect on the orifice in emergency, such as fore draining, freeing network vessels, harmonizing gi and blood, relieving pain, dispersing swelling and concretion, sedation, resolving toxin as well as strengthening the heart, relieving itching. So it has distinguished effect on all kinds of medical treatment to the modern people. But by the change of social customs and the confucianism of confucius - it is widely spread on the period of North and South Dynasties, 'Wi' and 'Jin' in china and the period of the Three States in korea - The blood-letting therapy which was regarded as the most important medicinal treatment withered rapidly. And Confucius accentuated the importance of our body and all its members, loyalty and filial piety and banned any damage of our body under no circumstances. As a result of it, the therapy of blood-letting had a rapid decrease and barely kept itself in existence in both countries. What is worse, at the period of Japanese colonial rule of korea and our nation's founding of early stage, it has been withered by the high-handed policy to change Oriental Medicine into modern medical science. So the therapy of blood-letting barely kept itself in existence in some Buddhist temples. Another case, it has handed down as a old-fashioned quick fix in folk remedies. But all kinds of the contamination of heavy metals and the misuses of antibiotics are widely spread nowadays, which increased diseases of adult people and incurable diseases as modern society unavoidably made its way into a highly industrial society. To make us more miserable, the western medical science - the antibiotics and surgical operation medical science - already reveals itself into a limit. The necessity of a new medical science which can give a security to the patients who are suffering from the diseases of adult people and the incurable diseases is especially come into the force nowadays. In view of the results after bibliographically studying on the blood-letting Therapy in Elementary Questions of the Yellow Emperor's Canon of Internal Medicine, the blood-letting therapy has acted for the important Oriental medicinal science and has been clarified the prominent effects on the diseases of adult people and the incurable diseases. So it is regarded as an appropriate thing that we lay out a determined theory of the blood-letting therapy and of course prevent the unwanted side effects from inappropriate medicinal treatments, and make full use of clinic by elevating the curative value and that we win back our self-respect of medical treatment which is dominated from the western medical science and ultimately contribute to national medical welfare.

• Journal of Chest Surgery
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• v.39 no.3 s.260
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• pp.220-225
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• 2006

Background: Spontaneous pneumomediastinum is an uncommon, benign, self-limited disorders that usually occurs in young adults without any apparent precipitating factors or disease. The purpose of this study was to review our experience in dealing with this entity and describe a reasonable course of assessment and management. Material and Method: A retrospective case series was conducted to identify adults patients with SPM who were diagnosed and treated in a single institution between 2001 and 2005. Result: Fifteen patients were identified who included 14 men and 1 women with a mean age of 26 years. Presenting symptoms were chest pain in 12 patients ($80\%$), dyspnea in 5 patients ($33\%$), and throat discomfort in 4 patients ($26\%$). Two cases were associated with use of inhalational drugs and 3 cases were associated with exercise. The predisposing factors were asthma, excessive exercise, and vomiting in spontaneous pneumomediastinum. The physical findings were subcutaneous emphysema in 10 patients ($77\%$). Chest radiography and computerized tomography were the diagnostic methods in all cases with CT scan revealing six cases with associated pulmonary abnormalities. Esophagogram and flexible bronchoscopy were selectively used. Fifteen patients ($100\%$) were admitted to the hospital. Their mean hospital stay was 3 days. All patients were conservatively treated. In a follow-up of 3 years no complications or recurrences were observed. Conclusion: Most simple spontaneous pneumomediastinum cases were benign diseases and most of them ($77\%$) had shown typical chest pain, dyspnea and subcutaneous emphysema. Inhalational drug use was not a major cause of SPM; however, increased use of bronchoinhalers was a suspicious cause of SPM.

• Journal of Chest Surgery
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• v.19 no.1
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• pp.35-42
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• 1986

Prevention of thrombombolism after rosthetic cardiac valve replacement is essential for the patients. About 90% of patients are free of major and minor thromboembolic complications 5 year after replacement of cardiac valves with prosthetic devices when they are under control of anticoagulant therapy. Ticlopidine is a drug that alter platelet function to have an antithrombotic effect. It is an antiaggregating agent which inhibits primary platelet function to have an antithrombotic effect. It is an antiaggregating agent which inhibits primary platelet aggregation induced by ADP and increases the production of prostaglandin $D_{2}$. Aspirin in small doses inhibits platelet synthesis of prostaglandins by irreversibly blocking the enzyme cyclo-oxygenase. Platelet secretion and aggregation are impaired with Ticlopidine and Aspirin. the thromboembolic event sof 54 patient s who were treated with Ticlopidine and Aspirin after cardiac valve replacement were evaluated and compared with that of 79 patients who were treated with Wafarin and Aspirin after the same type of operation. The follow-up period ranged from 4 to 110 months (mean of 48 months). there were 11 major thromboembolic episodes including three deaths in the warfarin goup during mean follow-up period of 56 months. two cases of CVA and one hemoarthrosis were noted due to overdose of Warfarin. Inticlopidine group, there was only one fatal thromboembolic epdisode three month after mitral valve replacement during mean follow-up period of 18 months. Two episodes of hypermenorrhea resulting anemia ere noted in the ticlopidine group. We measured the parameters of platelet function in aggreagation curve of platelet with platelet aggregometer (chrono-log Aggregometer, Model No. 430) Aggregation test was performed with three final concentrations of epinephrine in 10 uM/L, ADP in 5uM/L. 28 patients with prosthetic cardiac valves and 35 healthy volunteers were subgrouped as follows to analyze the effect of antithrombotic drugs used. Group I ; 11 patients treated with 250-500 mg of ticlopidine and 0.5gm of Aspirin as a daily single dose after cardiac valve replacement (14 St. Jude Medical and 1 Carpentier-Edwards, 9 patients with atrial fibrillation among them) Group II ; 10 patients treated with 3-5 mg of Warfarin and 0.75 gm of Aspirin daily to prolong prothrombin time around 20 seconds for more than 6 months and single Aspirin dose was maintained afterward as a life-long regimes(3 St. Jude Medical, 1 Hall-Kaster and 7 Carpentier-Edwards valve, 9 patients in atrial fibrilation). Group III ; 7 patients who quit anticoagulant treatment (Warfarin + Aspirin) 6-12 months after the regime as group II (3 St. Jude Medical. 1 bjork-Shiley, 1 Hall-Kaster, 3 Carpentier-Edwards valve, 2 of them are with atrial fibrillation). Group IV ; 35 healthy vounteers (28 males and 7 females). The following results were obtained. 1. The mean maximal platelet aggregability in Group I induced by 10uM/L epinephrine was 15.6%, and 17.5 and 18.7% in BM in proportion to the induction by 5 and 10 uM/L ADP. 2. The mean maximal platelet aggregability in Group II induced by 10uM/L epinephrine was 16.5%, and 27.4 and 44.7% in BM in proportion to the induction by 5 and 10uM/L ADP. 3. The mean maximal platelet aggregability in group III induced by 10uM/L epinephrine was 65%, and 56.5 and 51.8% in BM in proportion to the induction by 5 and 10 uM/L ADP. 4. The mean maximal platelet aggregability in the normal subjects induced by 10 uM/L epinephrine was 64%, and 65 and 69% in Bm inproportion to the induction by 5 and 10 uM/L ADP. 5. Reversible change of platelet aggregation curve induced by 5 and 10uM/L was noted all of the patients in Group I. conclusion : Ticlopidine is an antiaggregating agent which inhibits primary platelet aggregation induced by ADP, and increases the production of prostaglandin $D_{2}$. Ticlopidine and Aspirin produced a significant inhibition of platelet in the presence of ADP and epinephrine in our study. Acccording to our brief experience, 250 mg of ticlopidine and low dose of Aspirin resulted synergistic superior effect to each drug alone in prevention of thromboembolism after prosthetic cardiac valve replacement.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.213-225
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• 1989

An analysis has been made of two hundred seven patients who were treated at the department of Radiation Oncology of Korea University Hospital for lung cancer from January 1981 through December 1986. There were 137 patients of nonsmall cell carcinoma (137/207, 66%), 26 patients of small cell carcinoma (26/207, 12.5%) and 44 patients of unproven histology. By aims of treatment, there were 104 patients (104/207, 50%) treated for cure, 89 patients (89/207, 42.9%) for palliation and 14 patients treated postoperatively. In 22 out of 207 patients, chemotherapy was done with radiotherapy, 12 of which were patients with small cell carcinoma. Stage II patients were 49 (49/207, 23.6%), stage III patients were 157 (157/207, 75.8%) and one patient had an occult cancer The tumor was initial Iy measured by CAT scan and chest X-rays in the 165 (165/207, 79.7%) patients, among which 117 patients had tumor diameter more than 5cm and 48 patients less than 5cm. Radiation therapy was given with Cobalt 60 teletherapy unit and the treatment volume encompassed primary tumor and the mediastinum. For curative aim, daily tumor dose of 180 cGy was given up to the range of 5,400~6,120cGy/30~34F/6~7 week period and for palliative aim, daily tumor dose of 300 cGy was given up to the range of 3,600~4,500 cGy/12~15F/2~3 week period. Postoperatively, mediastinum was treated for total dose of 5,040 cGy/28F/5.5 week period. 123 patients (123/207, 59%) were followed up after completion of radiotherapy for 14 months to 7 years. Local tumor response to the irradiation was measured by chest X-ray taken at one month follow up and was evaluated for response rate, if they were regressed more than 50% or less than 50% of the initial tumor size. The treatment results were as follows; 1. The median survival time was 8.5 months and survival rates for 1 year, 2 year and 5 year was 25%, 3.5% and 1% of nonsmall cell lung ca of 74 evaluable patients. 2. More than 50% of local tumor response rate was obtained in about half of overall cases; 90.5% for small cell ca, 50% for squamous cell ca, 25% for adenoca and 57% for large cell ca. 3. Response rate more than 50% was seen in the 50% of the patient group with tumor diameter more than 5cm and in the 55% of those with tumor diameter less than 5cm. 4. By total raidation dose given, patient group which was given 5,400~6,120 cGy equivalent dose or higher showed tumor response rate more than 50% in 53% of the patients, whereas the group with dose less than 5,400cGy equivalent, in 25% of the patients. 5. Survival rate for 6 month, 1 year and 2 year was compared between the group of local tumor response rate more than 50% vs. group with response rate less than 50%; 74% vs. 43%, 33% vs, 23%, 10% vs. 1%, respectively. 6. Local failure was seen in 21%(44/207) of the patients, which occured mostly within 15 months after completion of radiation therapy. Distant metastases were seen in 49.7%(103/207) of the patients, of which 43 cases were found before initiation of radiotherapy. The most common metastatic sites were bone and brain. In this sutdy, 1 year,2 year and S year survival rates were somewhat poor compared to the other studies. It mainly seems to be due to the poor general status of the patients and the far-advanced stage of the disease. In nonsmall cell cancer patients who had limited local disease and had small primary tumor size, we observed better local response. In addition, dose higher than 6,000 cGy group showed better tumor control than lower dose group. Survival rate was better for the local control group. For imporvement of local control of the lung cancer and hence, the survival of the patients with lung cancer, proper radical radiotherapy with high dose for localized disease is needed. New modality of treatment such as high LET beam in radiation therapy or drugs for the advanced disease as well as early diagnosis is also needed.

• Journal of Veterinary Clinics
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• v.24 no.3
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• pp.300-304
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• 2007

The purpose of this study was to determine the anesthetic effects of tiletamine-zolazepam (TZ) alone and azaperone plus tiletamine-zolazepam in growing pigs, and to compare the various physiological parameters in both treatments. Cross experiment was accomplished at 2-week interval. Group 1 (TZ group): six pigs ($31.4{\pm}4.83$ kg) received 4.4 mg/kg of TZ alone. Group 2 (ATZ group); the same six pigs ($43.6{\pm}4.31$ kg) received 4.4 mg/kg of TZ twenty minutes after receiving 2 mg/kg of azaperone. All of the anesthetic drugs were injected into the trapezius muscles. The pigs were fasted for 24 hours before the experiments. Induction and recovery values were determined. Heart rate, respiratory rate, rectal temperature, $pO_2,\;pCO_2$ and pH were determined before administration and 5, 25, 45, 65 and 85 minutes after administration. Induction time of ATZ group was more rapid than that of TZ group (p<0.01). During recovery, sternal recumbency time, standing time and walking time of ATZ group were longer than those of TZ group (p<0.01). Heart rate, respiratory rate, $pO_2,\;pCO_2$, and pH did not show especial differences between the two groups. However, rectal temperature was significantly different between the TZ and ATZ group (p<0.05). As a result, ATZ group had a faster induction and a longer duration of anesthesia than TZ group did. Thus, it was concluded that ATZ combination could be usefully used for chemical restraint in pigs.

• 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.