• Title/Summary/Keyword: Multiple-dose

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Antiherpetic Activities of Natural Naringenin Alone and in Combinations with Acyclovir and Vidarabine (천연 나린게닌의 항허피스바이러스작용과 아시클로버 및 비다라빈과의 병용효과)

  • 이지현;김영소;이종길;이혁구;한성순
    • YAKHAK HOEJI
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    • v.43 no.1
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    • pp.77-84
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    • 1999
  • To search for less toxic antiherpetic agents, the inhibitory effects of natural naringenin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Naringenin inhibited plaque formations of HSV-l and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-l with selectivity index (SI) of 19.1 than on HSV-2 with SI of 5.7 The combined antiherpetic effects of naringenin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of naringenin with acyclovir on HSV-l and HSV-2 showed more potent synergism with CI values of 0.28∼0.81 for 50%, 70%, 90% effective levels than those with vidarabine with CI values of 0.86-3.28.

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Effect of Capsaicin on Delayed Rectifier $K^+$ Current in Adult Rat Dorsal Root Ganglion Neurons

  • Hahn, Jung-Hyun;Chung, Sung-Kwon;Bang, Hyo-Weon
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.1
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    • pp.9-14
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    • 2000
  • $K^+$ currents play multiple roles in the excitability of dorsal root ganglion (DRG) neurons. Influences on these currents change the shape of the action potential, its firing threshold and the resting membrane potential. In this study, whole cell configuration of patch clamp technique had been applied to record the blocking effect of capsaicin, a lipophilic alkaloid, on the delayed rectifier $K^+$ current in cultured small diameter DRG neurons of adult rat. Capsaicin reduced the amplitude of $K^+$ current in dose dependent manner, and the concentration-dependence curve was well described by the Hill equation with $K_D$ value of $19.1{\mu}M.$ The blocking effect of capsaicin was reversible. Capsaicin $(10 {\mu}M)$ shifted the steady-state inactivation curve in the hyperpolarizing direction by about 15 mV and increased the rate of inactivation. The voltage dependence of activation was not affected by capsaicin. These multiple effects of capsaicin may suggest that capsaicin bind to the region of $K^+$ channel, participating in inactivation process.

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Comparisons of Antidiabetic Effect of Panax Ginseng on MLD STZ-induced Diabetic rats in Terms of Time of Administration (Multiple Low Dose Streptozotocin으로 유도된 당뇨 흰쥐에서 투여 시기에 따른 인삼의 항당뇨 활성 비교)

  • Park, Kyeong-Soo;Lee, Dong-Eok;Sung, Jong-Hwan;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.26 no.4
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    • pp.191-195
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    • 2002
  • In this study, we like to examine whether Panax ginseng water extract (PGWE) exerts antidiabetic activities in prevention and treatment modes in multiple low dose (MLD) streptozotocin (STZ) (20 mg/kg i.p injection for 5 days) induced diabetic SD rats. In the prevention mode,150 mg/kg of GRWE was administered intraperitoneally with STG for 3 weeks, and this group is called CO 150. In the treatment mode, we started to administer the same dose of PGWE on day 8 and for 3 weeks, and this group is called POST150. PGWE exerted significant hypoglycemic activities in both prevention (normal control, 97 ${\pm}$ 6 mg/dl; diabetic control, 331${\pm}$23; CO150, 211${\pm}$37) and treatment groups (normal control, 128${\pm}$4 mg/dl; diabetic control, 392${\pm}$33: POST150, 263${\pm}$44). Of great importance is the fact that plasma insulin levels in both groups were markedly increased as compared to the diabetic control (normal control,428.7${\pm}$62.1 pg/dl; diabetic control, 167.0${\pm}$91.7; CO150, 377.6${\pm}$68.7 in prevention mode, and in treatment mode normal control 417.9${\pm}$84.6 pg/dl; diabetic control, 166.1${\pm}$104.7; POST150, 315.2${\pm}$47.4). Blood glucose levels were closely associated with plasma insulin levels, and this result may suggest that PGWE showed the activity to enhance insulin secretion as well as preventing destruction of pancreatic islet cells. Food and water intakes were also determined at the last week of treatment i n both groups. Characteristic symptoms of diabetes were significantly improved in both groups. In the prevention mode, water intake (ml/rat/day) in normal control was increased from 30.6${\pm}$1.5 to 122.2${\pm}$3.4 in diabetic control rats. In the CO150-treated group, water intake was dramatically reduced to 68.3${\pm}$4.4 (p<0.001 vs. diabetic control). In the treatment mode, POST-treated group also reduced the water intake from 128.9${\pm}$2.2 to 113.3${\pm}$1.7. Taken together, our data suggest that PGWE showed comparable antidiabetic activities in prevention and treatment modes. Therefore, PGWE may have a potential as a prophylactic as well as therapeutic agent fur type 2 diabetes mellitus (T2DM).

A Case of Drug-Induced Hepatitis due to Bortezomib in Multiple Myeloma

  • Kim, Young-Woon;Kim, Ka-Young;Lee, Su-Hyun;Chung, Yoon-Yung;Yahng, Seung-Ah;Lee, Sung-Eun;Park, Gyeong-Sin;Min, Chang-Ki
    • IMMUNE NETWORK
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    • v.12 no.3
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    • pp.126-128
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    • 2012
  • We report on a case of severe hepatotoxicity in a 52-year-old male with multiple myeloma (MM) who had received bortezomib therapy. At patient presentation, liver enzymes were normal, but started to markedly increase 3 days after the patient's second dose of bortezomib was administered, when free kappa light chains were noticeably reduced in the serum. After discontinuation of bortezomib, liver enzymes recovered gradually to baseline. Then, the patient was started on a thalidomide-containing regimen, which he was able to tolerate well. The patient achieved complete remission prior to autologous stem cell transplantation (ASCT). The patient underwent ASCT without occurrence of further liver toxicity.

Medulloblastoma and Familial Adenomatous Polyposis in a 24-year-old Female Patient: A Case Report of Turcot Syndrome (뇌수모세포종 및 가족성 선종성 용종증으로 발현한 Turcot 증후군 1예)

  • Jeong, Soo-In;Suh, Jung-Min;Lee, Ji-Hyuk;Lee, Hae-Jung;Lee, Jee-Hyun;Sung, Ki-Woong;Song, Hye-Jung;Choe, Yon-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.10 no.2
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    • pp.206-210
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    • 2007
  • Turcot syndrome is characterized by the concurrence of a primary neuroepithelial brain tumor and multiple colorectal polyposis. We report a case of a 24-year-old woman diagnosed with Turcot syndrome. At first, the patient was diagnosed as having a medulloblastoma after a tumorectomy of the 4th ventricle mass. The patient underwent radiotherapy and chemotherapy. After high-dose chemotherapy, neutropenic fever and severe mucositis developed. For an evaluation of the persistent hematochezia and diarrhea, a colonoscopy was performed. It revealed pseudomembranous colitis and multiple polyps in the entire colon. According to the family history, her father had undergone a total colectomy due to colon cancer and polyposis of the entire colon. Her brother also was found to have multiple polyps in the colon by a colonoscopy. The patient was diagnosed with Turcot syndrome.

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Multiple Small Nodular Lung Lesions with Severe Dyspnea (심한 호흡곤란을 보인 다발성 소결절성 폐질환)

  • Yang, Suck-Chul;Lee, Kyung-Sang;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Hahm, Shee-Young;Lee, Chul-Burm
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.285-290
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    • 1996
  • Diffuse panbronchiolitis is a chronic inflammatory lung disease of unknown etiology which is characterized by chronic airflow limitation and airway inflammation, predominantly localized in the respiratory bronchioles with infiltration of inflammatory cells, and has typical clinical, radiological and pathological features. Obstructive respiratory functional impairment, occasional symptoms of wheezing, and also cough and sputum resemble the feature of emphysema, bronchial asthma, or chronic bronchitis, respectively. We experienced a case of pathologically proven advanced diffuse panbronchiolitis in a 55-year-old man with productive cough and exertional dyspnea. The chest radiography showed multiple tiny nodular densities on whole lung fields. It was confirmed by thoracoscopy-guided lung biopsy and the patient was improved after initiation of treatment with low-dose erythromycin.

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Statatistical Analysis of Three Sequence-Three Periods Bioequivalence Study : Application to Bioequivalence Test of Ondansetron Formulations ($3{\times}3$ 라틴 방격법 모델에 따른 생물학적 동등성 시험의 통계 해석 : 온단세트론 제제에 대한 적용 예)

  • Lee, Young-Joo;Lee, Myung-Gull;Chung, Suk-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.28 no.1
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    • pp.35-42
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    • 1998
  • A $3{\times}3$ Latin square crossover study for the bioequivalence of three ondansetron formulations was conducted. Test products were $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg tablets and reference product was $Zofran^{\circledR}$ tablet. Twenty one healthy Korean male subjects received each formulation at the ondansetron dose of 8 mg and plasma concentrations of ondansetron were monitored by HPLC for over a period of 12 hr after the oral administration. Statistical procedure for bioequivalence evaluation of AUC {e.g., analysis of variance (ANOVA), multiple comparison and confidence intervals} was carried out. There were no significant differences in AUC among the formulations. The confidence intervals for the AUC of $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg were between -0.24 and 15.54% and between -2.41 and 13.36% respectively, within a range that proposed by the Korea Food and Drug Administration Guidelines for Bioequivalence. These statistical procedure could be standardized and generally applicable for the assessment of bioequivalence for multiple (more than two) formulations.

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Role of Oxytocin in Post-traumatic Stress Disorder: A Systematic Review (외상 후 스트레스 장애에 대한 옥시토신의 역할: 체계적 문헌 고찰)

  • Oh, Jaeuk;Kim, Minsu;Chu, Sang Hui
    • Journal of Korean Biological Nursing Science
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    • v.24 no.1
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    • pp.1-16
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    • 2022
  • Purpose: Recently, oxytocin has been introduced experimentally as a pharmacological treatment for post-traumatic stress disorder (PTSD). This study attempted to investigate the possibility of oxytocin as a treatment option for patients with PTSD by examining its dose, interval, and effectiveness in patients with PTSD. Methods: A systematic review was done on articles published from 1967 to 2020 using the PubMed, PsycINFO, and Cochrane databases. Our inclusion criteria were 1) subjects 18 years of age or older diagnosed with PTSD or exposed to a traumatic event that met criterion A of the Diagnostic and Statistical Manual of Mental Disorders (DSM) for PTSD, 2) oxytocin was administered at least once, 3) clinical trials, and 4) studies published in Korean or English. Two independent researchers reviewed 22 articles and recorded the contents. The risk of bias was evaluated to determine the quality of the reviewed article. Results: The parameters for evaluating the effectiveness of oxytocin were identified as socio-behavioral measures in 11 articles, neuronal imaging in 9, and biomarkers in 4. In 5 papers, oxytocin was administered multiple times. Socio-behavioral measures were improved in 3 out of 5 studies in which oxytocin was administered multiple times. In 2 studies in which prolonged exposure treatment and nasal oxytocin administration were combined for 10 weeks, patient symptoms were decreased compared to the control group. Conclusion: The possibility of oxytocin as an adjuvant treatment for PTSD psychotherapy was confirmed. Further studies are necessary to evaluate the long term effectiveness of administering oxytocin multiple times combined with psychotherapy.

Improved Breast Irradiation Techniques Using Multistatic Fields or Three Dimensional Universal Compensators (Multistatic Field또는 3차원 공용보상체를 사용한 유방의 방사선 조사법의 평가)

  • Han Youngyih;Cho Jae Ho;Park Hee Chul;Chu Sung Sil;Suh Chang-Ok
    • Radiation Oncology Journal
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    • v.20 no.1
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    • pp.24-33
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    • 2002
  • Purpose : In order to improve dose homogeneity and to reduce acute toxicity in tangential whole breast radiotherapy, we evaluated two treatment techniques using multiple static fields or universal compensators. Materials and Methods : 1) Multistatic field technique : Using a three dimensional radiation treatment planning system, Adac Pinnacle 4.0, we accomplished a conventional wedged tangential plan. Examining the isodose distributions, a third field which blocked overdose regions was designed and an opposing field was created by using an automatic function of RTPS. Weighting of the beams was tuned until an ideal dose distribution was obtained. Another pair of beams were added when the dose homogeneity was not satisfactory. 2) Universal compensator technique : The breast shapes and sizes were obtained from the CT images of 20 patients who received whole breast radiation therapy at our institution. The data obtained were averaged and a pair of universal physical compensators were designed for the averaged data. DII (Dose Inhomogeneity Index : percentage volume of PTV outside $95\~105\%$ of the prescribed dose) $D_{max}$ (the maximum point dose in the PTV) and isodose distributions for each technique were compared. Results : The multistatic field technique was found to be superior to the conventional technique, reducing the mean value of DII by $14.6\%$ (p value<0.000) and the $D_{max}$ by $4.7\%$ (p value<0.000). The universal compensator was not significantly superior to the conventional technique since it decreased $D_{max}$ by $0.3\%$ (p value=0.867) and reduced DII by $3.7\%$ (p value=0.260). However, it decreased the value of DII by maximum $18\%$ when patients' breast shapes fitted in with the compensator geometry. Conclusion : The multistatic field technique is effective for improving dose homogeneity for whole breast radiation therapy and is applicable to all patients, whereas the use of universal compensators is effective only in patients whose breast shapes fit inwith the universal compensator geometry, and thus has limited applicability.

Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.