• Title/Summary/Keyword: Multiple-dose

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Oxidized LDL is a Chemoattractant for the Eosinophils and Neutrophils (산화 저비중 리포 단백이 호산구와 호중구에 대한 화학주성)

  • Hwang, Young-Sil;Lee, Jong-Deog;Busse, William B.
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.3
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    • pp.211-223
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    • 2001
  • Background : Rhinovirus infection of the airways results in increased permeability of the airway vascular endothelium with the influx of plasma proteins, including lipids such as LDL. In vitro studies on the effect of oxLDL on leukocytes has shown many pro inflammatory effects on multiple leukocytes. We hypothesized that oxLDL is one mechanism for recruiting granulocytes to the airways during a RV infection. Therefore, chemotaxis and transendothelial migration, in response to nLDL, was determined for these granulocytes. Methods : nLDL was oxidized with 5mM Cu2S04 for 20-24 hours. 3-5 105 cells were loaded into the Transwell filter while the chemotatic agonists were placed in the lower well for chemotaxis. Confluent monolayers on HPMEC were grown on Transwell filters for transendothelial migration. The filters were washed and eosinophils and neutrophils loaded on to the filter with the chemotatic agonist was were placed in the lower well. The wells were incubated for 3 hours. The number of migrating cells was counted on a hemocytometer. Results : OxLDL, but not nLDL, is chemotatic for eosinophils and neutrophils. The level of granulocytes chemotaxis was dependent on both the concentration of LDL and its degree of oxidation. OxLDL stimulates eosinophil and neutrophils migration across HPMEC monolayers (+/-IL-$1{\beta}$ preactivation) in a dose dependent manner. Conclusion : Increased vascular permeability during a RV infection may lead to the influx and oxidation of LDL. The resulting oxLDL. is one possible mechanism for the recruitment of neutrophils and eosinophils to the airway interstitial matrix. Once in the airways, granulocytes can further interact with oxLDL to promote airway inflammation.

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The Role of Sympathetic Activity in the Early Phase of Liver Regeneration after Partial Hepatectomy (간-부분절제(肝-部分切除) 후 나타나는 재생과정(再生過程)에서 교감신경계(交感神經系)의 역할(役割)에 관(關)한 연구(硏究))

  • Choi, Sang-Hyun;Lee, Joong-Geun;Park, Chung-San;Chun, Boe-Gwun;Chun, Yeon-Sook
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.177-183
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    • 1990
  • This study was undertaken to confirm whether or not the sympathetic nervous system takes part in the liver regeneration after partial hepatectomy. The male Sprague-Dawley rats were pretreated with I.P. injection of guanethidine 25 mg/kg: single dose (G-1); multiple doses once a day for 3 days (G-3), for 5 days (G-5), or for 6 days (G-6). The rats were subjected to partial hepatectomy $(70.4{\pm}1.99%)$ under light anesthesia of diethyl ether. 1) The systolic blood pressure of control rat was $98.0{\pm}3.9\;mmHg$ and was not affected by G-1. But after the pretreatment with G-3, G-5 or G-6, the pressure was markedly decreased by over 25 %. 2) Both of plasma norepinephrine and epinephrine levels showed the marked increases 3 hrs after the hepatectomy. However, the increases are entirely inhibited by G-1 or G-6. 3) All the liver contents of putrescine, spermidine and spermine showed the significant increases 6 hrs after the hepatectomy and were not affected by G-1 or G-6 with the exception of the inhibition of putrescine increase by only G-6. The present results suggest that the sympathetic activation appeared after partial hepatectomy seems not to play an important role in rat liver regeneration.

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Action Mechanism of Antiestrogens on Uterine Growth in Immature Rats (자궁세포 성장에 미치는 항에스트로젠제의 작용기전)

  • Lee, Jung-Bin;Yoon, Mi-Chung;Kim, Chang-Mee;Hong, Sa-Suk;Ryu, Kyung-Za
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.167-176
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    • 1990
  • In the present study, we examined the effects of tamoxifen and LY117018 on various parameters for the estrogenic actions in order to understand the mechanism by which tamoxifen and LY117018 act on the uterine cells in 21-23 day old immature rats. Tamoxifen and LY117018 stimulated uterine weight and uterine contents of DNA, protein, and peroxidase activity in the absence of estradiol while inhibited above parameters in the presence of estradiol. Both cytosolic and nuclear progesterone receptors were increased by the treatment of tamoxifen and LY117018 as well as estradiol, but estradiol-induced increase in the progesterone receptors were reduced by the treatment of antiestrogens. These effects were enhanced by the multiple injections of antiestrogens. It seemed that tamoxifen was more agonistic than LY117018 but less antagonistic than LY117018, judged by their effects on various parameters for the estrogenic action. The affinities of estradiol, tamoxifen, and LY117018 for the estrogen receptor were $0.17{\pm}0.01nM(100%)$, $1.10{\pm}0.01nM(6.3%)$, and $0.23{\pm}0.01nM(77%)$, respectively. Furthermore, LY117018 was the competitive ligand for the estrogen receptor in dose-related manner but tamoxifen was not. Following estradiol treatment, nuclear estrogen receptor was sharply increased by 1 h, reaching the maximum by 16 h, while tamoxifen and LY117018 slightly increased nuclear estrogen receptor by 1 h and then decreased thereafter. It is therefore concluded that LY117018 is a competitive antagonist for the estrogen receptor with less estrogenic activity, compared to tamoxifen with low affinity to the estrogen receptor, and tamoxifen may act through other binding site than the estrogen receptor.

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Therapeutic compliance and its related factors in pediatrics patients (소아 환자의 치료 순응도 및 이에 영향을 미치는 요인)

  • Park, Ki Soo;Kam, Sin;Kim, Heung Sik;Lee, Jeong Kwon;Hwang, Jin-Bok
    • Clinical and Experimental Pediatrics
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    • v.51 no.6
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    • pp.584-596
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    • 2008
  • Purpose : This study was conducted to investigate treatment compliance and related factors in pediatric patients. Methods : Three hundred and fifty-five patients diagnosed with various acute diseases at a teaching hospital or clinic in October 2003 were enrolled. Data were analyzed using the Health Belief Model, which includes items on self-efficacy and family assistance. Results : The study found that 62.9% of pediatric patients adhered faithfully to agreed-upon hospital revisits, 41.6% complied with dose timings instructions, 65.8% precisely took medication, and 27.2% complied with all of these requirements. According to ${\chi}^2$ test analysis, the factors found to be related to therapeutic compliance (the taking of medicines requested) were; susceptibility, severity, benefit, barriers, mother's self-efficacy, and family assistance (P<.05). Multiple logistic analysis and path analysis showed that susceptibility, severity, barriers, and mother's self-efficacy were related to therapeutic compliance (P<.05). Moreover, mother's self-efficacy was identified as the most important factor. Conclusion : To improve therapeutic compliance among pediatric patients, parental education is necessary, and a health care professional must take a thorough history of how the medication was taken before it is assumed that treatment failure is attributable to the medication prescribed. Furthermore, the type of device recommended for dosing should be determined by clinicians. In addition, it is important that pediatric medications be discussed in relation to their palatability and internal acceptability.

Neurobehavioral Performance Test of Workers Exposed to Mixed Organic Solvents (복합유기용제에 폭로된 근로자들에 대한 신경행동학적 기능의 평가)

  • Kim, Chang-Youn;SaKong, Joon;Chung, Jong-Hak;Joo, Ree;Jeon, Man-Joong;Sung, Nag-Jung;Kim, Sang-Kyu
    • Journal of Yeungnam Medical Science
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    • v.14 no.2
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    • pp.314-328
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    • 1997
  • A cross-sectional study was performed to evaluate the effects of chronic exposure to low-dose solvent on neurobehavioral performance of 48 male workers exposed to organic solvents. A control group of 50 workers was selected from same factories. Each worker completed a medical and occupational questionnaire and four tests of Neurobehavioral Core Test Battery. These included Benton visual retention test, digit symbol, digit span, and pursuit aiming. Comparison of mean performance showed a significantly poorer performance on digit symbol, digit span, and pursuit aiming. In univariate analysis, age contributed to poor performance on Benton visual retention test and educational level was found to reduce the performance on symbol digit in both groups. Amount of alcohol intake was found to reduce the performance on digit symbol and smoking appeared to slow pursuit aiming in the exposure group. In multiple regression analysis, controlling for age, educational level, alcohol, and smoking, Solvent exposure was found to be associated with performance of digit span, and number of correct dot of pursuit aiming. Age on Benton visual retention, educational level on digit symbol, arid smoking on pursuit aiming were found to be a significant factors on each test items. This study suggest that short-term memory, and perception can be affected easily by chronic exposure of organic solvents which air concentration levels were under the Threshold Limit Value.

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The Adjuvant Effect of Subcutaneous Interferon-gamma in the Treatment of Refractory Multidrug-resistant Pulmonary Tuberculosis (난치성 다제내성 폐결핵에서 피하주사 Interferon-gamma 치료의 효과: 예비연구)

  • Kim, Eun Kyung;Shim, Tae Sun;Lee, Jung Yeon;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Dong Soon;Kim, Won Dong;Kim, Woo Sung
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.226-233
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    • 2004
  • Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

Induction of Apoptosis by Ethanol Extract of Lythrum anceps (Koehne) Makino in Human Leukemia U937 Cells (인체백혈병 U937 세포에서 부처꽃 에탄올추출물에 의한 apoptosis 유도)

  • Jeong, Jin-Woo;Kim, Chul Hwan;Lee, Young-Kyung;Hwang, Yong;Lee, Ki Won;Choi, Kyung-Min;Kim, Jung Il
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.279-286
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    • 2020
  • Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer effect are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins, depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

The Effects of Glucose, Insulin and Angiotensin II on Plasminogen Activator Inhibitor-1 Expression and Growth of Aortic Vascular Smooth Muscle Cell in Rats (포도당, 인슐린 및 Angiotensin II가 흰쥐 대동맥평활근세포의 Plasminogen Activator Inhibitor-1 발현 및 성장에 미치는 영향)

  • 최세영;이인규;한승세;김재현;박창권;이광숙;유영선;김기식;김윤년
    • Journal of Chest Surgery
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    • v.32 no.4
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    • pp.333-340
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    • 1999
  • Background: Plasminogen activator inhibitor-1(PAI-1) is known as the primary physiological inhibitor of tissue-type plasminogen activator(t-PA) in the plasma, and is present within the atherosclerotic vessels. Increased plasma levels of PAI-1 are one of the major disturbances of the hemostatic system in patients with diabetes and/or hypertension, and may have multiple interrelations with the important risk factors in the development of atherosclerosis. This study was performed to determine whether altered gene expression of PAI-1 occurs within the arterial wall, and thereby potentially contributing to the increase of cardiovascular risks associated with diabetes and/or hypertension. Material and Method: The aortic vascular smooth muscle cells of the rat were exposed to 22 mM glucose, angiotensin II, and insulin increased PAI-1 mRNA expression with the use of Northern blotting were examined. Also examined were the effects of 22 mM glucose, angiotensin II and insulin on the growth of the rat's aortic smooth muscle cells by using MTT assay. Result: Twenty-two mM glucose treatment increased the PAI-1 mRNA expression in a time- and dose-dependent manner. Aniotensin II treatment synergistically increased the glucose-induced PAI-1 mRNA expression. In contrast, addition of insulin attenuated the increase of 22 mM glucose and angiotensin II induced PAI-1 mRNA expression. Furthermore, treatment of 22 mM glucose, angiotensin II and insulin resulted in a significant increase in cell numbers. This study demonstrated that 22 mM glucose and angiotensin II have a synergistic effect in stimulating the PAI-1 mRNA expression and in the cell growth of the rat's aortic smooth muscle cells. Conclusion: Elevation of glucose and angiotensin II may be important risk factors in impairing fibrinolysis and developing atherosclerosis in diabetic patients.

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Preliminary Results of Management for Primary CNS Lymphoma (원발성 중추신경계 림프종의 치료에 관한 예비적 결과)

  • Ahn, Seung-Do;Chang, Hye-Sook;Choi, Eun-Kyong
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.79-82
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    • 1993
  • From October 1989 to March 1992, ten patients diagnosed as primary central nervous system (CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy & tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000 cGy/20 fx to the whole brain followed by an additional 2000 cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF involvement were treated with whole brain irradiation and intrathecal Methotrexate (IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to rodiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was $86{\%}\;and\;69{\%}$ respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.

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Adjuvant Radiotherapy Following Radical Hysterectomy and Bilateral Pelvic Lymph Node Dissection for the Uterine Cervical Cancer : Prognostic Factors and Failure Patterns (근칙적 절제술과 술후 방사선치료를 시행한 자궁경부암 환자의 치료성적, 예루인자와 실패양상)

  • Choi, Doo-Ho
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.357-367
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    • 1997
  • Purpose : To identify variable prognostic factors and analyse failure patterns in the uterine cervix cancer after radical operation and adjuvant radio-therapy, a retrospective analysis was undertaken. Materals and Methods : I analysed one hundred and twenty four patients with uterine cervix cancer, FIGO stage IB, IIA and IIB, treated with radical hysterectomy and pelvic lymph node dissection followed by adjuvant radio-therapy between May 1985 and May 1994. Minimum follow up period was 24 months. All of them were treated with full dose external radiotherapy with linear accelerator and/or high dese rate intracavitary radiation. Results : Overall 5 year survival rate and relapse free survival rate were $75.4\%,\;73.5\%$, respectively. Significant prognostic factors by relapse free survival were wall involvement thickness, lymph node location and number, parametrium involvement, tumor size, stage, uterine body involvement, vaginal resection margin involvement. By multivariate analysis, lymph node matastasis. tumor size and vaginal resection margin involvement were significant prognostic factos. Treatment related failure were 33 cases. Locoregional failure were more likely in the stage IIB, lymph node positive or vaginal resection margin positive patients whereas distant failures were relatively more frequent in stage IB, IIA and lymph node, vaginal resection negative patients. In stage IIB, 5 year relapse free survival rate was only $56\%$ and nine of twenty two patients recurred. Conculsion : Postoperative radiotherapy results are good for patients with relatively low risk factor. But the results are poor for patients with multiple, high risk factors or stage IIB. To control recurrence for patients with high risk factors, postoperative adjuvant radiotherapy is not sufficient treatment method. To raise control rate adding other methods such as radiosensitizing agent or chemotherapy is necessary and prospectively randomized study is needed for evaluation of postoperative radiotherapy efficacy and /or other methods. And it is reasonable to treat primary radical radiotherapy for patients with stage IIB cervical cancer instead of radical operation and adjuvant radiotherapy and/or chemotherapy regimen.

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