• Title/Summary/Keyword: Drug Development

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An Investigation of Glyceollin I's Inhibitory Effect on The Mammalian Adenylyl (글리세올린 I의 아데니닐 고리화 효소 활성 억제 효능과 결합 부위 비교 분석)

  • Kim, Dong-Chan;Kim, Nam Doo;Kim, Sung In;Jang, Chul-Soo;Kweon, Chang Oh;Kim, Byung Weon;Ryu, Jae-Ki;Kim, Hyun-Kyung;Lee, Suk Jun;Lee, Seungho;Kim, Dongjin
    • Journal of Life Science
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    • v.23 no.5
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    • pp.609-615
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    • 2013
  • Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.

Effect of Powder of Stevia rebaudiana Leaves against Quality Characteristics during Salting of Rice Bran Danmooji (쌀겨단무지의 절임 중 품질 특성의 변화에 대한 스테비아 잎 분말 첨가의 영향)

  • Kim, Yong-Suk;Lee, Sun-Kyu;Jeong, Do-Yeong;Yang, Eun-Jin;Shin, Dong-Hwa
    • Food Science and Preservation
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    • v.14 no.5
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    • pp.497-503
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    • 2007
  • In order to develop a new rice bran danmooji, changes in physicochemical characteristics and texture of danmooji treated with rice bran, Stevia rebaudiana Bertoni leaf powder, succinic acid, or yeast extract were investigated during salting for 90 days. The PH of rice bran danmooji decreased from PH6.41 initially to pH 4.09 (control group), pH 4.10 (S. rebaudiana treatment S1), pH 3.84 (S. rebaudiana + succinic acid treatment S2), and pH 3.90 (S. rebaudiana+succinic acid+yeast extract treatment S3) after 90 days of salting. At this time, the salinities of rice bran danmooji of the S1, S52, and S3 groups were 2.32%, 1.94% and 2.15% respectively. The hardness of all groups decreased rapidly in the first 30 days of salting, and thereafter showed no changes. After 90 days of salting, the hardness of all groups was $1,186-1,368\;g/cm^2$ with no significant differences between groups. Redness, the a value, of the S2 and S3 groups treated with succinic acid, was lower than that of S3, whereas yellowness, the b value, of S3 treated with succinic acid and yeast extract was the highest of the three groups. Sensory evaluation of rice bran danmooji after 90 days of salting resulted in S3 attaining the highest scores for flavor, taste, texture, and overall acceptability. These results indicate nut high-quality rice bran danmooji may be prepared by addition of S. rebaudiana leaf powder, succinic acid and yeast extract to rice bran.

The Evaluation and Development of Head and Neck Radiation Protective Device for Chest Radiography in 10 Years Children (소아(10세) 흉부 방사선촬영에서의 두경부 방사선 방어기구 개발 및 평가)

  • Lee, Jun Ho;Lim, Hyun Soo;Lee, Seung Yeol
    • Journal of Radiation Protection and Research
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    • v.40 no.2
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    • pp.118-123
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    • 2015
  • The frequency of diagnostic radiation examinations in medical institutions has recently increased to 220 million cases in 2011, and the annual exposure dose per capita was 1.4 mSv, 51% and 35% respectively, compared to those in 2007. The number of chest radiography was found to be 27.59% of them, the highest frequency of normal radiography. In this study, we developed a shielding device to minimize radiation exposure by shielding areas of the body which are unnecessary for image interpretation, during the chest radiography. And in order to verify its usefulness, we also measured the difference in entrance surface dose (ESD) and the absorbed dose, before and after using the device, by using an international standard pediatric (10 years) phantom and a glass dosimeter. In addition, we calculated the effective dose by using a Monte Carlo simulation-based program (PCXMC 2.0.1) and evaluated the reduction ratio indirectly by comparing lifetime attributable risk of cancer incidence (LAR). When using the protective device, the ESD decreased by 86.36% on average, nasal cavity $0.55{\mu}Sv$ (74.06%), thyroid $1.43{\mu}Sv$ (95.15%), oesophagus $6.35{\mu}Sv$ (78.42%) respectively, and the depth dose decreased by 72.30% on average, the cervical spine(upper spine) $1.23{\mu}Sv$ (89.73%), salivary gland $0.5{\mu}Sv$ (92.31%), oesophagus $3.85{\mu}Sv$ (59.39%), thyroid $2.02{\mu}Sv$ (73.53%), thoracic vertebrae(middle spine) $5.68{\mu}Sv$ (54.01%) respectively, so that we could verify the usefulness of the shielding mechanism. In addition, the effective dose decreased by 11.76% from $8.33{\mu}Sv$ to $7.35{\mu}Sv$ before and after wearing the device, and in LAR assessment, we found that thyroid cancer decreased to male 0.14 people (95.12%) and female 0.77 people (95.16%) per one million 10-year old children, and general cancers decreased to male 0.14 people (11.70%) and female 0.25 people (11.70%). Although diagnostic radiation examinations are necessary for healthcare such as the treatment of diseases, based on the ALARA concept, we should strive to optimize medical radiation by using this shielding device actively in the areas of the body unnecessary for the diagnosis.

Anti-diabetic effect and mechanism of Korean red ginseng extract in C57BL/KsJ db/db mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Proceedings of the Ginseng society Conference
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    • 2007.12a
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    • pp.57-58
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    • 2007
  • Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

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Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model (LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과)

  • Kim, Ji-Hye;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Cho, Kwang-Su;Kim, Go-Eun;XU, Xiaotong;Lee, Da-Hye;Park, Ga-Ryeong;Ahn, Dong-Hyun
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1149-1157
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    • 2017
  • Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

Effects of Recombinant Human Epidermal Growth Factor (rhEGF) on Experimental Radiation-Induced Oral Mucositis in Rats (Rat의 방사선 조사성 구내염에 대한 Recombinant Human Epidermal Growth Factor (rhEGF)의 효과)

  • Jung Kwon-Il;Kim Sun-Hee;Moon Soo-Young;Kim Yeon-Wha;Hong Joon-Pio;Kim Hyun-Sook;Lee Sang-Wook
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.67-76
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    • 2006
  • Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

Smad6 Gene and Suppression of Radiation-Induced Apoptosis by Genistein in K562 Cells (K562 세포주에서 Genistein에 의해 억제되는 Radiation-induced Apoptosis의 조절 유전자)

  • Jeong, Soo-Jin;Jin, Young-Hee;Yoo, Yeo-Jin;Do, Chang-Ho;Jeong, Min-Ho;Huh, Gi-Yeong;Bae, Hye-Ran;Yang, Kwang-Mo;Moon, Chang-Woo;Oh, Sin-Geun;Hur, Won-Joo;Lee, Hyung-Sik
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.245-251
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    • 2001
  • Prupose : The genes involved on the suppression or radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. Materials and methods : K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For X-ray irradiation and drug treatment, cultures were prepared at $2\times10^5\;cells/mL$. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA), Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at $37^{\circ}C$ for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. Results : Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. Conclusion : We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.

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Development of Anti-diabetes Drink Using with Silkworm(Bombyx mori L.) Extract (누에(Silkworm) 추출물을 이용한 기능성 항당뇨음료의 개발)

  • 최진호;김대익;박시향;백승진;김남주;류강선
    • Journal of Sericultural and Entomological Science
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    • v.45 no.2
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    • pp.96-102
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    • 2003
  • This study was designed to develope the functional anti-diabetes drink, Dia-D using silkworm (Bombyx mori L) extract Sprague-Dawley (SD) male rats (160${\pm}$10g) were fed basic diet (control group), and experimental diets (SWE-l0, 30, 60 groups and Daonil-40, 80 groups) added silkworm extract 10, 30 and 60mg/day or diabetes drug prepared and marketed by Handok Pham. Co., Daonil 40 and 80 mg/day for 12 days. Blood glucose contents were significantly decreased 25-30% in SWE-30 and SWE-60 groups, and about 35% in Daonil 40 and Daonil 80 groups compared with control group. Triglyceride (TG) and lipid peroxide (LPO) contents were significantly inhibited 10-16% and 8-13%, respectively, in SWE-30 and 60 groups, whereas these contents were 13-30% and 15%, respectively, in Daonil-40 and 80 groups compared with control group. Hydroxyl radical (OH) contents were significantly inhibited 19-20% in SWE-30 and 60 groups, and 7-12% in Daonil-40 and 80 groups compared with control group. Superoxide dismutase (SOD) activities were significantly increased 11-14% in SWE-30 and 60 groups, and 12-29% in Daonil-40 and 80 groups compared with control group. In results of clinical test using normal subjects, blood glucose content tested in NIAST subjects as anti-diabetes drink, Dia-D willi 100mg/vial was significantly decreased 17.5%, and these content tested in PKNU subjects as anti-diabetes drink, Dia-D with 150mg/vial was significantly decreased 20.5% compared with control group. These results suggest that administration of Dia-D as an anti-diabetes drink prepared with silkworm extract may playa very effective role in a decreasing of blood glucose in hyperglycemia patients.

Physiological Activity and Physicochemical Properties of Condensed Prunus mume Juice Prepared with Pectinase (Pectinase처리를 한 매실 농축액의 이화학적 특성 및 생리활성)

  • Kim, Jeong-Ho;Cho, Hyun-Dong;Won, Yeong-Seon;Park, Wool-Lim;Lee, Kwan-Woo;Kim, Hyuk-Joo;Seo, Kwon-Il
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1369-1378
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    • 2018
  • Prunus mume Siebold & Zucc., a member of the Rosaceae family (called Maesil in Korea), has been widely distributed in East Asia, e.g. Korea, Japan and China, and its fruit has been used as a traditional drug and health food. In this study, we evaluated physicochemical properties and physiological activities of condensed Prunus mume juice treated with pectinase (PJ). The values of total acidity, pH, sugar contents, turbidity moisture content of the PJ were 35.81%, 2.73, $54.36^{\circ}Brix$, 2.75 and 51.32%, respectively. The PJ had effective DPPH radical scavenging activity, reducing power effect, $H_2O_2$ scavenging activity and ${\beta}$-carotene bleaching effect. DPPH radical scavenging activities of PJ was 46.31%; their reducing power ($OD_{700}$) was 1.80; $H_2O_2$ scavenging activity of PJ was 91.62%; and ${\beta}$-carotene bleaching effect of PJ was 73.02%. Also, PJ showed effective levels of ${\alpha}$-glucosidase inhibition activity. The cell viability was measured by SRB assay. The PJ significantly decreased the cell viability of mouse melanoma cells (B16) and human melanoma cells (SK-MEL-2 and SK-MEL-28) in a dose-dependent manner, however, there was no effect on human keratinocyte HaCaT. In morphological study, PJ-treated SK-MEL-2 cells showed distorted and shrunken cell masses. Total polyphenol contents and total flavonoid contents of PJ were 588.31 mg% (gallic acid equivalent) and 860.45 mg% (rutin equivalent). The antiproliferative effect of PJ seems to be associated with the antioxidant activity of its flavonoid and polyphenol contents. In conclusion, PJ may be beneficial in development of a functional food material.

Clozapine Administration Potentiate Platelet Activation in Patients with Schizophrenia : Retrospective Study (클로자핀을 투여한 조현병 환자에서 혈소판 활성 증가에 관한 후향적 연구)

  • Kim, Hyun-Ah;Lee, Jong Wook;Kim, Seung-Jun;Oh, Hong-Seok;Im, Woo Young;Kim, Ji-Woong
    • Korean Journal of Psychosomatic Medicine
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    • v.26 no.2
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    • pp.188-193
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    • 2018
  • Objectives : Clozapine is a widely prescribed antipsychotic drug for schizophrenia and is known to increase the risk of cardiovascular disease due to its metabolic side effects. However, little is known about the effect of clozapine on the platelet activation, another important factor in the development of cardiovascular disease. In this study, we tried to investigate the effect of clozapine on platelet activity in patients with schizophrenia by comparing the mean platelet component (MPC) values before and after the clozapine administration. Methods : A retrospective review of medical records of patients with schizophrenia, who newly started clozapine treatment from September 1st, 2003 to April 30th, 2007 at the Department of Psychiatry, Konyang University Hospital in Republic of Korea was performed. The final statistical analysis included 14 participants. Bayer ADVIA $120^{(R)}$ system was used to measure MPC. Results : Among the 14 participants, five subjects were males (28.60%), and ten subjects were females (71.40%). The mean age of participants was $37.50{\pm}11.64years$. Average of duration of illness was $91.00{\pm}93.96months$, with the mean dosage of clozapine taken by participants at the time of the last blood test was $337.50{\pm}109.52mg$. The mean MPC measurement before and after receiving clozapine was $26.12{\pm}2.22g/dL$ and $25.14{\pm}2.08g/dL$ respectively. Wilcoxon signed rank test showed that there was a statistically significant decrease in MPC levels after clozapine administration (V=16, p=0.024). Conclusions : Decreased MPC levels after clozapine administration implies that clozapine may increase platelet activation which could have an adverse effect on the occurrence of thromboembolic disease. Our findings also suggest that careful monitoring of the risk factors of cardiovascular diseases, such as platelets activity, is necessary when administering clozapine.