• Journal of Ginseng Research
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• 제43권2호
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• pp.218-225
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• 2019

Background: Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (${{\Delta}}pep27$) has been shown to confer comprehensive, long-term protection against even nontypeable strains. However, ${{\Delta}}pep27$ is effective as a vaccine only after at least three rounds of immunization. Therefore, treatments capable of enhancing the efficiency of ${{\Delta}}pep27$ immunization should be identified without delay. Panax ginseng Mayer has already been shown to have pharmacological and antioxidant effects. Here, the ability of Korean Red Ginseng (KRG) to enhance the efficacy of ${{\Delta}}pep27$ immunization was investigated. Methods: Mice were treated with KRG and immunized with ${{\Delta}}pep27$ before infection with the pathogenic S. pneumoniae strain D39. Total reactive oxygen species production was measured using lung homogenates, and inducible nitric oxide (NO) synthase and antiapoptotic protein expression was determined by immunoblotting. The phagocytic activity of peritoneal macrophages was also tested after KRG treatment. Results: Compared with the other treatments, KRG significantly increased survival rate after lethal challenge and resulted in faster bacterial clearance via increased phagocytosis. Moreover, KRG enhanced ${{\Delta}}pep27$ vaccine efficacy by inhibiting reactive oxygen species production, reducing extracellular signal-regulated kinase apoptosis signaling and inflammation. Conclusion: Taken together, our results suggest that KRG reduces the time required for immunization with the ${{\Delta}}pep27$ vaccine by enhancing its efficacy.

• Tuberculosis and Respiratory Diseases
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• 제43권4호
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• pp.579-589
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• 1996

연구배경 : 패혈증에서 백혈구의 활성화는 미생물 및 숙주 독성 물질의 청소에 중요한 역활을 하며 한편으로 활성화된 호중구와 그의 특성 물질은 조직 손상파 장기의 기증 부전을 초래한다. 백혈구의 CD11/18 유착 분자는 감염 및 염증 부위로 호중구 이동의 첫 단계인 호중구-내피 세포 유착을 조절한다. 패혈증 치료 전락으로 호중구 억제 효과의 가능성을 알아보기 위해 rat 에서 Escherichia coli 폐렴을 유발하여 CD11b에 대한 단클론 항체(MAb 1B6)의 효과를 평가하였다. 방법 : 1 mg/kg CD11b에 대한 단클론 항체와 1 mg/kg BSA출 폐렴 유발 6 시간전, 유발시 및 유발 6 시간후 무작위적으로 피하 투여하였다. 폐렴 유발후 무작위적으로 24, 60 및 90%의 산소를 투여하였으며 폐렴 유발후 4시간 및 3일간 하루에 한번씩 100 mg/kg의 ceftriaxone을 투여하였다. 말초 및 폐포 호중구와 폐 손상의 지표인 D(A-a)O2, W/D LW ratio 및 폐포 세척액 단백 농도를 12시간과 96시간까지 생존한 동물에서 측정하였다. 결과 : CD11b에 대한 단클론 항체는 말초 및 폐포 호중구를 감소시켰으며 96시간 보다 12시간에 더욱 감소시켰다. 폐손상 지표는 단클론 항체 투여군과 대조군을 비교시 차이를 보이지 앉았으나 생존 동물 수의 부족으로 통계학적 평가의 의미가 없었다. 조기(6 시간) 사망률은 항체 투여군 51%로 대조군 31%보다 의미(P=0.02) 있게 증가하였으나 후기 사망률(12 시간에서 72 시간)은 항체 투여군 44% 대조군 36%로 의미(P=0.089) 있는 차이가 없었다. 결론 : CD11b/18 유착 분자는 감염 및 염증 부위로 호중구의 이동을 조절하는 것으로 알려져 있다. CD11b에 대한 단클론 항체는 rat의 폐인성 패혈증에서 폐포 호중구를 감소시키고 조기 사망률을 증가시켰다. 따라서 CD11b에 대한 단클론 항체가 rat의 폐인성 패혈증의 초기에 호중구의 폐포내 이동을 억제시켜 숙주의 방어 기전에 장애를 초래하여 조기 사망률을 증가시키는 것으로 사료된다.

• 대한핵의학회지
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• 제23권1호
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• pp.55-61
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• 1989

While cisplatin has been widely used in the treatment of a variety of cancers, nephrotoxicity is one of the major problems which frequently limit clinical usefulness of cisplatin. This study has been conducted to investigate nephrotoxicity of cisplatin in terms of changes in glomerular filtration rate (GFR) and effective renal plasma flow (EFPF) measured by the simultaneous use of $^{99m}Tc-DTPA$ and $^{131}I-OIH$, before and after administration of cisplatin, in 12 patients with lung cancer and four patients with esophageal cancer. Cisplatin was administrated at total doses of $75\sim100mg/m^2$ with two hour hydration and diuresis method. GFR determined by the use of $^{99m}Tc-DTPA$ had a good correlation with 24-hour creatinine clearance rate (r=0.77, p<0.001). GFR and filtration fraction decreased immediately after administration of cisplatin, however, they showed a tendency to be in completely recovered four weeks after administration. ERPF was not changed immediately after and four weeks after administration of cisplatin. GFR before and immediately after administration of cisplatin were analyzed with regard to age, sex, performance status, previous adminstration of cisplatin and method of administration. None of these factors had any influence on the rate of decrease in GFR except method of administration. Administration of cisplatin as a single dose lowered GFR more compared with that as divided doses. In this study, we have also demonstrated that the simultaneous use of $^{99m}Tc-DTPA$ and $^{131}I-OIH$ was a useful tool for the measurement of GFR and ERPF respectively.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• 대한방사성의약품학회지
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• 제4권2호
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• pp.65-72
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• 2018

Prostate specific membrane antigen (PSMA) is a cell surface membrane protein, which is overexpressed in most prostate cancer. Recently, PET imaging with $[^{68}Ga]$PSMA-HBED-CC has been widely used for the diagnosis of recurrent prostate cancer and the studies on the diagnostic potential of $^{64}Cu$-labeled PSMA ligands reported actively. In this study, we monitored with biological evaluation in vivo and PET imaging of $^{64}Cu$-labeled PSMA ligand ($[^{64}Cu]$PSMA-617). The radiolabelling efficiency and stability of $[^{64}Cu]$PSMA-617 were confirmed by radio-thin layer chromatography. The radiolabeling efficiency of $[^{64}Cu]$PSMA-617 showed over 95%, and stabilities of intact remained over 98% in both human and mouse serum for 48 h. In normal male mice, in vivo uptake of $[^{64}Cu]$PSMA-617 in several organs was measured at 2, 4, 6, 24, 48 h after injection. Rapid blood clearance was observed for $[^{64}Cu]$PSMA-617. The high uptake was observed in the lung, liver, intestines and kidneys at 2 h postinjection, but was low in the other organs (1-2 %ID/g) at 4 h. The dynamic PET/CT images of 22RV1 tumor-bearing nude mice were acquired during 60 min and additionally acquired 24 h and 48 h after injection. In dynamic PET images, $[^{64}Cu]$PSMA-617 uptake ratio in tumors versus muscle was increased as time elaplsed until 60 minutes and remained in tumors at 48 h. In these results, the PET/CT imaging using $[^{64}Cu]$PSMA-617 in prostate cancer is expected to be useful for the diagnosis and treatment of prostate cancer patients.

• 혜화의학회지
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• 제8권2호
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• pp.211-243
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• 2000

This study was performed to investigate the cause, symptom, treatment, medicine of Wei symptom through the literature of oriental and western medicine. The results obtained were as follows: 1. Wei symptom is the symptom that reveals muscle relaxation without contraction and muscle relaxation occures in the lower limb or upper limb, in severe case, leads to death. 2. Since the pathology and etiology of Wei symptom was first described as "pe-yeol-yeop-cho"(肺熱葉焦) in Hung Ti Nei Ching(黃帝內經), for generations most doctors had have accepted it. but after Dan Ge(丹溪), it had been classified into seven causes, damp-heat(濕熱), phlegm-damp(濕痰), deficiency of qi(氣虛), deficiency of blood(血虛), deficiency of yin(陰處), stagnant blood(死血), stagnant food(食積). Chang Gyeng Ag(張景岳) added the cause of deficiency of source qi(元氣). 3. The concept of "To treat Yangming, most of all"(獨治陽明) was emphasized in the treatment of Wei symptom and contains nourishment of middle warmer energy(補益中氣), clearance of yangming-damp-heat(淸化陽明濕熱). 4. Since Nei-ching era(內經時代), Wei and Bi symptom(痺症) is differenciated according to the existence of pain. After Ming era(明代) appeared theory of co-existence of Wei symptom and pain or numbness but they were accepted as a sign of Wei symptom caused by the pathological factor phelgm(痰), damp(濕), stagnancy(瘀). 5. In the western medical point of view, Wei symptom is like paraplegia, or tetraplegia. and according to the causative disease, it is accompanied by dysesthesia, paresthsia, pain. thus it is more recommended to use hwal-hyel-hwa-ae(活血化瘀) method considering damp-heat(濕熱), qi deficiency of spleen and stornach(脾胃氣虛) as pathological basis than to simply differenciate Wei and Bi symptom according to the existence of pain. 6. The cause of Gullian-Barre syndrome(GBS) is consist of two factors, internal and external. Internal factors include asthenia of spleen and stomach, and of liver and kidney. External factors include summur-damp(暑濕), damp-heat(濕熱), cold-damp(寒濕) and on the basis of "classification and treatment according to the symptom of Zang-Fu"(臟腑辨證論治), the cause of GBS is classified into injury of body fluid by lung heat(肺熱傷津), infiltration of damp-heat(濕熱浸淫), asthenia of spleen and kidney(脾腎兩虛), asthenia of spleen and stomach(脾胃虛弱), asthenia of liver and kidney (肝腎兩虛). 7. The cause of GBS is divided by according to the disease developing stage: Early stage include dryness-heat(燥熱), damp(濕邪), phlegm(痰濁), stagnant blood(瘀血), and major treatment is reducing of excess(瀉實). Late stage include deficiency of essence(精虛), deficiency with excess(虛中挾實), and essencial deficiency of liver and kidney(肝腎精不足) is major point of treatment. 8. Following is the herbal medicine of GBS according to the stage. In case of summur-damp(暑濕), chung-seu-iki-tang(淸暑益氣湯) is used which helps cooling and drainage of summer-damp(淸利暑濕), reinforcement of qi and passage of collateral channels(補氣通絡). In case of damp-heat, used kun-bo-hwan(健步丸), In case of cool-damp(寒濕), used 'Mahwang-buja-sesin-tang with sam-chul-tang'(麻黃附子細辛湯合蓼朮湯). In case of asthenia of spleen and kidney, used 'Sam-lyeng-baik-chul san'(蔘笭白朮散), In case of asthenia of liver and kidney, used 'Hojam-hwan'(虎潛丸). 9. Following is the herbal medicine of GBS according to the "classification and treatment according to the symptom of Zang-Fu"(臟腑辨證論治). In the case of injury of body fluid by lung heat(肺熱傷津), 'Chung-jo-gu-pae-tang'(淸燥救肺湯) is used. In case of 'infiltration of damp-heat'(濕熱浸淫), us-ed 'Yi-myo-hwan'(二妙丸), In case of 'infiltration of cool-damp'(寒濕浸淫), us-ed 'Yui-lyung-tang', In case of asthenia of spleen, used 'Sam-lyung-bak-chul-san'. In case of yin-deficiency of liver and kidney(肝腎陰虛), used 'Ji-bak-ji-hwang-hwan'(知柏地黃丸), or 'Ho-jam-hwan'(虎潛丸). 10. Cervical spondylosis with myelopathy is occuered by compression or ischemia of spinal cord. 11. The cause of cervical spondylosis with myelopathy consist of 'flow disturbance of the channel points of tai-yang'(太陽經兪不利), 'stagnancy of cool-damp'(寒濕凝聚), 'congestion of phlegm-damp stagnant substances'(痰濕膠阻), 'impairment of liver and kidney'(肝腎虛損). 12. In treatment of cervical spondylosis with myelopathy, are used 'Ge-ji-ga-gal-geun-tang-gagam'(桂枝加葛根湯加減), 'So-hwal-lack-dan-hap-do-hong-eum-gagam(小活絡丹合桃紅飮加減), 'Sin-tong-chuck-ue-tang-gagam(身痛逐瘀湯加減), 'Do-dam-tang-hap-sa-mul-tang-gagam'(導痰湯合四物湯加減), 'Ik-sin-yang-hyel-guen-bo-tang'(益腎養血健步湯加減), 'Nok-gakyo-hwan-gagam'(鹿角膠丸加減). 13. The cause of muscle dystropy is related with 'the impairement of vital qi'(元氣損傷), and 'impairement of five Zang organ'(五臟敗傷). Symptoms and signs are classified into asthenia of spleen and stomach, deficiency with excess, 'deficiency of liver and kidney'(肝腎不足) infiltration of damp-heat, 'deficiency of qi and blood'(氣血兩虛), 'yang deficiency of spleen and kidney'(脾腎陽虛). 14. 'Bo-jung-ik-gi-tang'(補中益氣湯), 'Gum-gang-hwan'(金剛丸), 'Yi-gong-san-hap-sam-myo-hwan'(異功散合三妙丸), 'Ja-hyel-yang-gun-tang'(滋血養筋湯), 'Ho-jam-hwan'(虎潛丸) are used for muscle dystropy. 15. The causes of myasthenia gravis are classified into 'insufficiency of middle warmer energy'(中氣不足), 'deficiency of qi and yin of spleen and kidney'(脾腎兩處), 'asthenia of qi of spleen'(脾氣虛弱), 'deficiency of qi and blood'(氣血兩虛), 'yang deficiency of spleen and kidney'(脾腎陽虛). 16. 'Bo-jung-ik-gi-tang-gagam'(補中益氣湯加減), 'Sa-gun-ja-tang-hap-gi-guk-yang-hyel-tang'(四君子湯合杞菊地黃湯), 'Sa-gun-ja-tang-hap-u-gyi-eum-gagam'(四君子湯合右歸飮加減), 'Pal-jin-tang'(八珍湯), 'U-gyi-eum'(右歸飮) are used for myasthenia gravis.

• Radiation Oncology Journal
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• 제11권2호
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• pp.295-301
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• 1993

절제 불가능한 제 3기 비소세포 폐암에서의 MVP(Mitomycin C 6 $mg/m^2$, Vinblastine 6 $mg/m^2$, Cisplatin 60 $mg/m^2$) 복합 항암요법과 다분할 방사선 치료의 효과를 판정하기 위하여 1991년 1월부터 전향성 임의 선택연구(prospective randomized study)를 시작하였다. 본 연구는 제 III기의 비소세포 폐암중 절제가 불가능한 환자를 대상으로 하여 MVP 항암요법을 3 회 시행한 후 다분할 방사선 치료 (120 cGy/fx, BID)를 6480 cGy까지 시행하였다. 방사선 치료가 끝난 1개월 후 유도 항암요법에 부분 관해 이상의 반응을 보였던 환자를 대상으로 추가 항암요법을 시행하는 군과 계속 관찰하는 군으로 임의 분류하였다. 1992년 12월까지 48명의 환자가 등록되었으며, 이중 3명은 항암요법후 치료를 중단하였으며, 6명은 방사선 치료중 치료를 중단하거나, 개인적 사정으로 다분할 방사선 치료를 시행받지 못하여 39명의 환자에 대한분석을 시행하였다. 유도 항암요법을 마친 환자중 2명은 완전 관해를 보였으며, 21명은 부분 관해를 보여 MVP 유도항암요법에 대한 관해율은 $58\%$ (23/39)이었다. 항암요법에 부분관해를 보인 21명중 1명은 방사선 치료후 완전관해를 보였으며, 10명은 부분관해를 보였으나, 나머지 10명은 방사선 치료에 반응을 보이지 않았다. 항암요법에 반응을 보이지 않았던 16명의 환자중 9명은 방사선 치료에도 전혀 반응을 보이지 않았다. 유도항암 요법과 다분할 방사선 치료후의 관해율은 $64\%$이었다. 방사선 치료후 19명의 환자에 대하여 추가 항암요법에 대한 임의 선택을 시행하여 이중 9명은 추가 항암요법 군으로 분류되어, 3회의 추가 항암요법을 시행하였다. 아직까지는 추가 항암요법군과 관찰군 사이에 원격전이나 생존율의 차이가 관찰되지 않았다. 전체 환자의 중앙 생존은 13개월이었고, 6개월과 12개월의 생존율은 각각 $84.6\%$와 $53.7\%,\;40.3\%$이었다. 특히 유도항암요법에 부분관해 이상의 반응을 보였던 환자들은 무반응환자에 비하여 통계적으로 유의하게 증가된 생존율을 보였다(p=0.0287). 아직까지 추적 관찰기간이 짧으나, $64\%$의 높은 치료 관해율과 증가된 생존율, 그리고 합병증의 증가가 관찰되지 않는 점으로 보아 본 연구를 계속 진행함으로써 더 좋은 결과를 얻을 수 있을 것으로 기대된다.