• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Sleep Medicine and Psychophysiology
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• v.8 no.2
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• pp.107-112
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• 2001

Introduction: Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, is known to be closely associated with the human leukocyte antigen (HLA) DQB1*0602. Several studies have suggested that HLA-DQB1*0602 is strongly linked with narcolepsy-cataplexy. However, no studies have yet been made on whether HLA DQB1*0602 is associated with Korean patients with narcolepsy. This study was designed to investigate the frequency of HLA-DQB1*0602 of Korean patients with narcolepsy. Methods: Twenty patients were selected (mean age: $28.2{\pm}3.0$, 11 men and 9 women). The patients were confirmed to have narcolepsy by the overnight polysomnography and multiple sleep latency test (MSLT) in addition to their clinical history and symptoms at St. Vincent's Hospital and Korea University Hospital Sleep Disorders Clinic. Any subjects co-morbid with other hypersomnic sleep disorders such as sleep apnea or periodic limb movements during sleep were excluded. Clinical data was collected through a semi-structured interview for narcoleptic patients. All patients and 21 control did HLA typing for the presence of DQB1*0602. Results Obtained were as Follows: 1) Mean sleep latency was 2.4 (${\pm}2.0$ minutes) and mean frequency of sleep-onset REM period was 3.0 (${\pm}1.6$) by MSLT. 2) Characteristic symptoms of narcolepsy investigated were as follows: excessive daytime sleepiness (100%), cataplexy (100%), sleep paralysis (60%), hypnagogic hallucination (70%) and disrupted nocturnal sleep (75%). 3) Strong emotional expression such as laughing (80%) and joking (70%) triggered cataplexy which affects the knee and leg region (80%) and jaw region (30%). 4) HLA-DR2 was found in 90% of patients and 35% in controls. The frequency of HLA-DQB1*0602 in patients and controls was 90%, and 24%, respectively. Conclusions: These results, which exhibit high HLA-DQB1*0602 expression in Korean patients with narcolepsy, suggest that HLADQB1*0602 could be a strong genetic marker in narcolepsy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.1
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• pp.15-20
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• 2006

The water and $40\%$ ethanol extracts from mulberry fruits were tested for their antimicrobial activities against Helicobacter pylori and antioxidant. Kangwon III (Morus albba L.) was higher phenolic content (2.90 mg/g) than other water extracts. The phenolic contents of $40\%$ ethanol extracts from Kangwon III and Hihak were 3.02 mg/g and 2.46 mg/g, respectively . The ABTS [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfornic acid)] radical decolorization, electron donating ability (EDA), thiobarbituric acid reactive substance (TBARS) and antioxidant protection factor (PF) were determined for water extracts and $40\%$ ethanol extracts from mulberry fruits. EDA was higher in water extracts than ethanol extract. EDA of water extract from Kangwon III was determined as $99.54\%$ while the activity of ethanol extracts was $89.61\%$ in Daechoukmyeun. The water extracts from Cheongilppong showed higher antioxidative activity than another mulberry fruits extract when evaluated by ABTS [2,2'-azinobis(3-ethylbenzothiaznoline-6-sulfornic acid)] radical decolorization, TBARS and antioxidant PF by water extracts. Kangwon III was higher phenolic content (2.90 mg/g) than other that of water extracts. $40\%$ ethanol extracts were determined that phenolic contents of Kangwon III, Hihak were 3.02 mg/g, 2.46 mg/g for each other. Antimicrobial activity showed the high value in water extracts of Cheongilppong, Kuksang 20. The result will be useful nature microbial medicine for mulberry fruits.

• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.571-578
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• 2001

To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

• Neonatal Medicine
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• v.16 no.2
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• pp.190-196
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• 2009

Purpose: Candida infection has increased in neonatal intensive care units (NICU). However, recent reports on systemic candida infections in preterm newborns are rare in Korea. The aim of this study was to examine the epidemiological features of systemic candida infection in very low birth weight infants (VLBW) over the past five years. Methods: We retrospectively reviewed the medical records of 19 patients with systemic candida infections in VLBW that were admitted to the neonatal intensive care units of three hospitals affiliated with the College of Medicine, The Catholic University of Korea from January 2004 to December 2008. We analyzed the birth weight, gestational age, age at diagnosis, risk factors, co-morbidity, antifungal treatment, and mortality rates among the 19 patients. Results: Systemic candida infections occurred in 19 cases (4.7%) among the VLBW infants. The mean birth weight and gestational age were 959.0$\pm$255.9 g and 26.7$\pm$2.1 weeks. The isolated Candida species were C. albicans (4), C. parapsilosis (9), C. glabrata (2), C. famata (2), and unkown subspecies (2). Most patients had various associated risk factors, including a central venous catheter, broad spectrum antibiotics, parenteral nutrition, intravenous lipid emulsion, endotracheal intubation and $H_2$ blocker therapy. There was no significant difference in the risk factors between newborns that survived and those that died with regard to the systemic candida infection, except for gestational age. Nine (47.4%) out of 19 patients with a candida infection died and four cases (21.2%) were directly related to the candida infection. Conclusion: The prevalence of systemic candida infection is increasing in VLBW infants. The majority of Candida species has shifted to C. non-albicans, especially C. parapsilosis. Because of the high mortality associated with candida infection in the NICU, prophylaxis and early treatment based on epidemiological features is necessary.

• Korean Journal of Plant Resources
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• v.20 no.5
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• pp.383-388
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• 2007

This study examined the effective treatment method of selenium and translocation characteristics of selenium in order to produce mungbean containing selenium. The foliar application of selenium at 3.5, 7, 14, and $28mg/{\ell}$ during the flowering period, yielded a relatively high record of seeds containing $0.41{\sim}3.96mg/kg$ and $0.27{\sim}2.38mg/kg$ of selenium, from the first and second harvesting. However, seeds from the first harvesting contained $52{\sim}71%$ more selenium than the seeds from the second harvesting. On the other hand, seeds from first and second harvesting of the non-treatment group had the same amount of selenium at 0.02mg/kg only. When the foliar application of selenium at $7mg/{\ell}$ was conducted two or three times, seeds from the first to third harvesting contained just the equal amount of selenium. However, when it was conducted only once, seeds from the first harvesting contained 56% and 67% more than seeds from the second and third harvesting, respectively. In seeds of mungbean containing 2.05mg/kg of selenium, cotyledon had 2.99mg/kg of selenium, which was 38% more than seed coat per unit weight. When mungbean sprout was produced, selenium content was 5.51mg/kg, but seed coats by-product of sprouts had 0.78mg/kg of selenium. The growth and quantity of mungbean was not significantly different according to the concentration and the frequency of foliar application of selenium used for in study.

• Journal of the Korean Crystal Growth and Crystal Technology
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• v.34 no.4
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• pp.109-116
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• 2024

β-Ga₂O₃ is a representative ultra-wide bandgap (UWBG) semiconductor that has attracted much attention for power device applications due to its wide-bandgap of 4.9 eV and high-breakdown voltage of 8 MV/cm. In addition, because solution growth is possible, it has advantages such as fast growth rate and lower production cost compared to SiC and GaN [1-2]. In this study, we have successfully grown Si-doped 10 mm thick Si-doped β-Ga₂O₃ single crystals by the EFG (Edge-defined Film-fed Growth) method. The growth direction and growth principal plane were set to [010] / (010), respectively, and the growth speed was 7~20 mm/h. The as-grown β-Ga₂O₃ single crystal was cut into various crystal planes (001, 100, ${\bar{2}}01$) and off-angles (1^o, 3^o, 4^o), and then surface processed. After processed, the homoepitaxial layer was grown on the epi-ready substrate using the HVPE (Halide vapor phase epitaxy) method. The processed samples and the epi-layer grown samples were analyzed by XRD, AFM, OM, and Etching to compare the surface properties according to the crystal plane and off-angle.

• Applied Biological Chemistry
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• v.22 no.2
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• pp.65-90
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• 1979

This study was conducted to establish the brewing method which would be useful for the production of Kochuzang. Kojis, which were made from various materials and microorganisms under a covered condition, were investigated and compared. Yeasts (Saccharomyces rouxii and Torulopsis versatilis) were added to Kochuzang, and the enzyme activity, microflora, chemical composition, nitrogen content, alcohol content and free sugars of Kochuzang were investigated and analysed. The results obtained are as follows: 1. Koji making (1) Glutinous rice-soybean group was superior to glutinous rice group in the saccharogenic and liquefying amylase activities of three day-Koji. (2) Protease activity (acid, neutral and alkaline) of glutinous rice-soybean Koji, which was inoculated with Aspergillus oryzae A, was increased till the 5th day, while other groups showed maximum activity after the 3rd day. (3) The maximum cellulose activity of Aspergillus oryzae B-Koji and A-Koji was observed after the 2nd day and the 3rd day, respectively. High cellulose activity of Aspergillus oryzae B-Koji and A-Koji was respectively shown in glutinous rice group and glutinous rice-soybean group at maximum. (4) Compared with glutinous rice Koji, glutinous rice-soybean Koji gave larger number of yeast and aerobic bacteria. 2. Kochuzang Fermentation (1) Each Kochuzang group shoved different liquefying and saccharogenic amylase activities. The highest activities were generally shown in 10 to 40 days after mashing and remarkably reduced in the last stage of aging. (2) Protease activities of each group were strong in order of acid, neutral and alkaline protease. Especially acid protease showed highest activity at the 40th to 50th day Kochuzang. (3) Each group showed maximum cellulase activity in the 40th and 50th day-Kochuzang and then decreased. (4) Osmophilic yeast of yeast-added Kochuzang after one-month aging was distinctively outnumbered compared with non-yeast-added Kochuzang, but two groups were similar after two months. (5) Yeast-added group and non-added group gave almost the same number of halophilic lactic acid bacteria in Kochuzang, but the non-added group gave slightly larger number of aerobic bacteria than the yeast-added group. (6) Amino nitrogen contents in all test group were increased rapidly till the 60th day of Kochuzang aged. After that the contents were increased slowly. (7) Ethyl alcohol contents of 20day-fermented Kochuzang were high in order of Saccharomyces rouxii-added group, Torulopsis versatilis-added group, Saccharomyces rouxii and Torulopsis versatilis mixed group and non-yeast-added group. But all test group showed about 2% in ethyl alcohol content after 40days of aging. (8) Alcohol content in the 7 month-aged Kochuzang of all test groups was high in order of ethyl alcohol, n-butyl alcohol, n-propyl alcohol and iso-propyl alcohol. Torulopsis versatilis-added group had the highest value of ethyl alcohol, n-propyl alcohol and n-butyl alcohol. (9) Reducing sugar in Kochuzang was increased after 20 days of aging compared with the 10days-ferment. The reducing sugar content in Saccharomyces rouxii-added group was distinctively small compared with that of other groups, decreasing after 30days of aging. (10) Rhamnose, fructose, glucose and maltose were isolated from the 10 day fermented Kochuzang. Raffinose was also found after 300 days-aged group, and fructose content was high in the 300days-aged Kochuzang. However, glucose content was smaller than that of 10days-fermented Kochuzang. (11) For the organoleptic tests of Kochuzang, taste, flavour and color of yeast-added group were superior to the non yeast-added group. Especially the complex yeast group among the yeast added groups were the best of all. Yeast-added group after 300 days of aging took higher paint in flavour test than that of non-added group. Therefore, brewing method like complex yeast added group seems to be advantageous for short time brewing Kochuzang.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.12
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• pp.1726-1733
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• 2011

We performed a randomized placebo-controlled trial to determine whether or not Ishige okamurae extract supplements modulate blood glucose and antioxidant systems in type 2 diabetic patients. A total of 46 patients were randomized to either an Ishige okamurae extract group or a placebo group. The patients consumed either 1,600 mg of Ishige okamurae extract or cornstarch supplement per day for 10 weeks. The lifestyle factors and dietary intake of patients were not altered during the 10 week trial period. After 10 weeks, the fasting blood glucose level was slightly decreased in the Ishige okamurae extract group, but a significant decrease was not observed. Also, glycosylated hemoglobin was significantly (p<0.01) decreased. Especially, low-glycosylated hemoglobin ($7.12{\pm}0.38%$ to $6.56{\pm}0.53%$) was significantly decreased compared to high-glycosylated hemoglobin ($8.65{\pm}0.92%$ to $8.60{\pm}0.85%$) in that group. The superoxide dismutase, catalase, and glutathione peroxidase levels were increased in the Ishige okamurae extract group compared to the placebo group. The increase of these enzymes was associated with the decrease of MDA concentration in the Ishige okamurae extract group, but a significant decrease was not observed. The Ishige okamurae extract supplement showed no adverse effects on liver and kidney functions. Findings from this study suggest that an Ishige okamurae extract supplement can help blood glucose status in type 2 diabetic patients without adverse effects.

• Korean Journal of Medicinal Crop Science
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• v.9 no.2
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• pp.156-165
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• 2001

Exogeneous application of pokeweed antiviral protein (PAP), a ribosomal-inacivating protein in the cell wall of Phytolacca americana (pokeweed) protects heterologous plants from viral and fungal infection. A cDNA clone of PAP introduced into Scrophularia buergeriana Miquel by thransformation with Agrobacterium tumefaciences. For plant transformation, explants were precultured on shoot induction medium without kanamycin for 2-5 day, and then they were cocultured with Agrobacterium for 10 minutes. The explants were placed on co culture medium in dark condition, $28^{\circ}C$ for 2days. After explants were washed in MS liquid medium, they were transferred into selection medium including kanamycin 50mg/L (MS salts+1mg/ l BAP+2mg/ l TDZ+0,2mg/ l NAA+MS vitamin+3% sucrose+0.8% agar, pH5.8). From PCR analysis, NPT II band was confirmed in transgenic plant genome and showed resistance against fungi in antifungal activity test. Micro assay to which protein extracted from transgenic line were added, revealed hyphae growth inhibition and no spore germination at high concentration. The characteristics of inhibited hyphae was represented transparent and thin. Expression of PAP in transgenic plants offers the possibility of developing resistance to viral and fungal infection.