• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.251-256
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• 1996

Kartagener's syndrome, a congenital disease transmitted as an autosomal recessive illness with a prevalence of approximately 1:20,000 persons, is characterized by the triple association of situs inversus, bronchiectasis, and sinusitis. Affected persons have an incoordination of ciliary motility that leads to defective mucociliary transport, chronic bronchial infections. Kartagener's syndrome is a subset of the immotile cilia syndrome and therefore all patients with Kartagener's syndrome have immotile cilia with obvious ultrastructural defects in the ciliary axoneme. In the respiratory tract this inability presumably causes impaired clearance of mucus and inhaled particles and results in the chronic infections of the sinuses and bronchial trees that are characterized of the disease. The end-stage phenomenon in Kartagener's syndrome, respiratory or heart failure is a less common event and heart-lung transplantation is becoming an accepted therapy for patients with end-stage pulmonary disease in Kartagener's syndrome in many institutes. We report one case of Kartagener's syndrome in a 25-year-old young woman who was presented as respiratory and right heart failures, with review of literatures.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.317-334
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• 2002

Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

• Journal of Ginseng Research
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• v.43 no.2
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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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• v.43 no.4
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• pp.579-589
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• 1996

Background : Activation of neutrophil is critical for the clearance of microorganisms and toxic host mediators during sepsis. Unfortunately the activated neutrophil and its toxic byproducts can produce tissue injury and organ dysfunction. The leucocyte CD11/18 adhesion complex regulates neutrophil-endothelial cell adhesion, the first step in neutrophil migration to sites of injection and inflammation. To investigate the potential of neutrophil inhibition as a treatment strategy for sepsis, we evaluated the effects of monoclonal antibody against CD11b (MAb 1B6) in rats intrabronchial challenged with Escherichia coli. Methods : Animals were randomly assigned to receive monoclonal antibody against CD11b (1 mg/kg, sc) and bovine serum albumin(BSA, 1 mg/kg, sc) 6 hr before, at 0 and 6 hr after intrabronchial challenge of $20x10^9$ CFU/kg E. coli 0111. Animals were randomized to treat either 24, 60 or 90% oxygen after bacterial challenge and begining 4 hr after inoculation, all animals were received 100 mg/kg ceftriaxone qd for 3 days. Peripheral and alveolar neutrophil(by bronchoalveolar lavage) counts and lung injury parameters such as alveolar-arte rial $PO_2$ difference, wet to dry lung weight ratio and protein concentration of alveolar fluid were measured in survived rats at 12 hr and 96 hr. Results : Monoclonal antibody against CD11b decreased circulating and alveolar neutrophil especially more in 12 hr than in 96 hr The lung injury parameters of antibody-treated animals were not different from those of BSA-treated animals. but It was meaningless due to small number of survived animals. The early(6 hr) mortality rate was significantly increased in antibody-treated group(51%) compared to BSA-treated group(31%) (P=0.02) but late(from 12 hr to 72 hr) mortality rate was not different in antibody-treated group(44%) from BSA-treated group(36%) (P =0.089). Conclusion : Leucocyte CD11b/18 adhesion molecule is known to regulate neutrophil migration to the site of infection and inflammation. The monoclonal antibody against CD11b decreased alveolar neutrophil in rats with pulmonary sepsis and increased early mortality rate. Therefore, we can speculate that monoclonal antibody against CD11b blocks of alveolar recruitment of neutrophils, impairs host defense mechanism and increases early mortality rate of pulmonary sepsis in rat.

• The Korean Journal of Nuclear Medicine
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• v.23 no.1
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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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• v.5 no.3
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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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• v.40 no.2
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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.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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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.

• Journal of Haehwa Medicine
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• v.8 no.2
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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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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.