Blocking of Cell Proliferation, Cytokines Production and Genes Expression Following Administration of Cordyceps Sinensis in the Bronchoalveolar Lavage Fluids Cells

Kuo, Yuh-Chi,Wu, Chia-Lin,Tasi, Wei-Jern,Wang, Jir-Yenn,Chang, Shi-Chung,Lin, Ching-Yuang,Shiao, Ming-Shi 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Yuh-Chi Kuo¹,Chia-Lin Wn¹,Wei-jern Tasi¹,Jir-Yenn Wang²,Shi-Chung Chang₃,Ching-Yung Lin⁴,and Ming-Shi Shiao⁴¹National Research Institute of Chinese Medicine, ²Department of Biology,Fu Jen University, ³Department of Chest, ⁴Department of Pediatrics, □De[art,amt of Medical Research and Education. Taipei Veterans General Hospital, Taipei, Taiwan Yuh-Chi Kuo¹,Chia-Lin Wn¹,Wei-jern Tasi¹,Jir-Yenn Wang²,Shi-Chung Chang²,Ching-Yung Lin³,and Ming-Shi Shiao⁴.¹National Research Institute of Chinese Medicine, ²Department of Biology,Fu Jen University, ³Department of Chest, ⁴Department of Pediatrics, □De[art,amt of Medical Research and Education. Taipei Veterans General Hospital, Taipei, Taiwan. Blocking of Cell Proliferation, Cytokines Production and Genes Expression Following Administration of Cordyceps sinensis in the Bronchoalveolar Lavage Fluids Cells. Proceedings of international Symposium on East-West Medicine, Seoul. 44-64, 1999.-Cordyceps sinensis is a major parasitic fungus on larva of Lepidoptera. It is one of the well know fungi used in traditional Chinese medicine for treatment asthma, lung and kideney diseases. Many fungi belonging to the genus Cordyceps have been demonstrated to produce natural products with various biological activities. Reported biological activities of genus cordyceps include:(a)inhibition of DNA and RNA synthesis;(b)enhancement of cell differentiation;(c)restruction of cytoskeleton;(d)inhibition of protein kinase activity;(e)antitumor activity on bladder, colon, lung carcinoma as well as fibroblastoma;(f)inhibition of the infection and revers transciptase activity of human immunodeficiency virus type 1; and(g) inhibition of methylation of nucleic acid. Thus, it is suggested that the extracts of Cordyceps sp. Contain antitumor, antiviral, and many other biological activities. In our previous studies, we proved that C. sinensis contains the antitumor and immunomodulatory agents. In the present studies, effects of C. sinensis on bronchoalveolar lavage fluids(BAL)cells were demonstrated. The crude methanolic extracts of C. sinensis were fractionated into 15 fractions by silica gel column chromatography. Effects of various fraction on BAL cells proliferation and lipopolysaccharide(LPS) stimulated interleukin-1β(IL-8),platelet activating factor(PAF), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α),and interleukin-8(IL-8) production on BAL cells were determined. The result indicated that the CS-19-22 fraction suppressed BAL cells proliferation activated by LPS. The median inhibitory concentration(IC50) was 6㎍/ml. The CS-19-22 fraction also decreased IL-1β,PAF,IL-6, TNF-αand IL-8 production.The results of revers transcription-polymerase chain reaction(RT-PCR) demonstrated that the CS-19-22 fraction did not affect IL-1β,PAF,IL-6, TNF-α,and IL-8 mRNAs expression in BAL cells activated by LPS. By contrast, it inhibited the IL-10 mRNA expression but enhanced IFN-γand IL-12 mRNAs expression in activated BAL cells. Moreover, the CS-19-22 fraction blocked PAF-induced platelet aggregation. It is unlikely that cytotoxicity was involved. Because no cell deths were observable. We hypothesize that inhibitory mechanisms of CS-19-22 on BAL cells proliferation may be related to the impairments of gene expression and production of cytokines in BAL cells. The explanation of C. sinensis antiasthma function may involved the following(1)C.sinenesis contained immunomodulatory agents that stimulated IFN-γand IL-12 expression in TH1cells.(2)Enhanced secretion of IFN-γand IL-12 will inhibit the Tγcells immune responses Ex. Decreasing of IL-6 and IL-10 production.(3) The impairments of cytokines production in TH2 cells suppressed th BAL cells proliferation then more cytokines production Ex.IL-1β,PAF,IL-6,TNF-αand IL-8 in activated BAL cells were decreased. (4)The suppression of TH2cells immune responses will inhibit the growth and differentiation of B cells then IgE production will be decreased. (5)Reduced production of IgE will decreased asthma attack occurring in individuals. However, the results of the present study suggested that C. sinensis may also have acted to treat asthma in part by inhibiting BAL cells proliferation and cytokine gene expression and production. Future, experiments with treatment of animals with asthma with C. sinensis will be necessary to defined whether C. sinensis can reduce asthma injury. Plans are underway for the isolation of pure principal growth inhibitors and their mechanisms of action are subjected for further study.

물류 유통을 최적화하기 위한 네트워크-유통 알고리즘의 설계

김명하, 이충세 충북대학교 컴퓨터정보통신연구소 2008 컴퓨터정보통신연구 Vol.16 No.1

-본문참고-

비글개에서 신원방우황청심원의 급성 및 아급성독성시험

성하정,권오경,방명주,곽형일,이진영,신대희,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of New wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs (3 males and 3 females) in acute experiments were administered orally with sinlge dose of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NSCH, 160 ㎎/㎏/day (low dosage group), 400 ㎎/㎏/day (middle dosage group), 1,000 ㎎/㎏/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ per oral for both male and females. In animals administered with NSCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NSCH in beagle dogs is considered to be safe.

비글개에서 신우황청심원의 급성 및 아급성독성시험

권오경,성하정,곽형일,방명주,신대희,이진영,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of New Woohwangchungsimwon (NWCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NWCH, 160 ㎎/㎏/day(low dosage group), 400 ㎎/㎏/day (middle dosage group), 1,000 ㎎/㎏/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ per oral for both male and females. In animals administered with NWCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NWCH in beagle dogs is considered to be safe.

비글개에서 l-muscone의 급성독성 및 아급성독성시험 연구

유아선,권오경,성하정,곽형일,방명주,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of l-muscone, a major active ingredient of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dosage of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of l-muscone, 0.2㎎/㎏/day(low dosage group), 2 ㎎/㎏/day(middle dosage group), or 20 ㎎/㎏day(high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korean Food and Drug Administration(1996.4.16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ on oral route for both male and females. In animals administered with l-muscone, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight and other findings. No histolopathological lesions were observed in both control and treatment groups. Above data strongly suggest that l-muscone in beagle dogs is considered to be safe.

물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가

김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

Time-degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among HCV Patients: A Model for Prioritization of Treatment

( Ming-lung Yu ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Chia-yen Dai ),( Wan-long Chuang ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma (HCC) over time. We aimed to explore their impac at the initiation of antiviral therapy on HCC among chronic hepatitis C (CHC) patients. Methods: A total of 1281 biopsy-proven CHC patients receiving interferon- based therapy were followed for a mean period of 5.5 years. Results: The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients who were <40 years old (7.7 % vs. 0.5%, P=0.1), but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P<0.001) and >55 years old (15.1% vs. 7.9%, P=0.03). Compared with SVR, non-SVR was independently predictive of HCC in patients 40-55 years old (hazard ratio [HR]/95% confidence intervals [CI]: 10.92/3.78-31.56, P<0.001) and >55 years old (HR/CI: 1.96/1.06-3.63, P=0.03) but not in patients <40 years old (HR/CI: 2.76/0.41-18.84, P=0.3). The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%, P=0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%, P<0.001) or F4 (33.5% vs. 8.4%, P=0.002). Compared with SVR, non-SVR was independently predictive of HCC in patients with F2-3 (HR/CI: 4.36 /2.10-9.03, P<0.001) and F4 (HR/CI: 3.84/1.59-9.30, P=0.03) but not in those with F0-1 (HR/CI: 1.53/ 0.49-4.74, P=0.47). Conclusions: Delayed HCV clearance for patients with CHC > 40 years old or with a fibrosis stage > 2 increases the risk of HCC over time.

Application of neuro-fuzzy algorithm to portable dynamic positioning control system for ships

Ming-Chung Fang,Zi-Yi Lee 대한조선학회 2016 International Journal of Naval Architecture and Oc Vol.8 No.1

This paper describes the nonlinear dynamic motion behavior of a ship equipped with a portable dynamic positioning (DP) control system, under external forces. The waves, current, wind, and drifting forces were considered in the calculations. A self-tuning controller based on a neuro-fuzzy algorithm was used to control the rotation speed of the outboard thrusters for the optimal adjustment of the ship position and heading and for path tracking. Time-domain simulations for ship motion with six degrees of freedom with the DP system were performed using the fourth-order RungeeKutta method. The results showed that the path and heading deviations were within acceptable ranges for the control method used. The portable DP system is a practical alternative for ships lacking professional DP facilities.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Inhibition of Skin Irritant Reaction by (-)-Epigallocatechin-3-gallate

Ming jin · Hyang-Hoon Cho · Myung-Sub Chung · PN Amatya · S Acharya · Kee-Hune Kim · Hyun-Chul Ha · Young-Jin Jeon 조선대학교 의학연구원 2006 The Medical Journal of Chosun University Vol.31 No.2

.