加減茵蔯蒿湯 水鍼液이 膽道結紮로 유도된 肝損傷에 미치는 영향

成樂箕,金元信,田炳薰,李建穆 대한동의병리학회 1993 동의생리병리학회지 Vol.8 No.-

연구배경 : 肝癌 및 肝硬變은 韓國人의 疾病으로 인한 중요한 喪亡原因의 하나이며, 특히 우리나라 B型肝炎의 流行地域으로 急慢性 肝炎이나 肝經辨證, 肝癌의 發病率이 높다. 그리하여 肝硬變症을 寢具治療法중 水鍼을 이용하여 肝의 募穴인 期門穴에 投與하면 治療效果가 있는지에 대하여, 그리고 藥量에 따라 治療效果가 달라지는 지에 대하여 알아보기 위하여 본 연구를 시행하였다. 방법 : 加減茵蔯蒿湯 水鍼液을 膽道를 結紮한 白鼠에 26guage의 1ml 주사기를 이용하여 투여하였다. 經穴은 人體의 期門에 相應하는 左石部位와 腹部內의 任意의 部位를 設定하여 매일 1회 7주간 수침하였다. 결과 : 體重과 Total Bilirubin은 實驗群 A, C에서 有意性 있는 增加와 減少를 보였고, WBC·ALT·AST·ALT 및 Cholesterole은 全實驗群에서 有意性 있는 減少를, Albumin은 全實驗群에서 有意性 있는 增加를 각각 나타내었으며, 組織學的 觀察도 全實驗群에서 有意性을 나타내었다. 또한 Hydroxyproline도 實驗群 A, B에서 有意性있는 減少를 보였다. 결론 : 加減茵蔯蒿湯 水鍼液을 膽道를 結紮한 白鼠의 期門穴에 投與한 缺課 有意한 효과를 보였으나 水鍼量에 따라 有意性의 차이가 있어 敵意한 水鍼量을 투여하는 것이 治療시 重要하다고 思料되며, 또한 水鍼에 대한 安全性 問題에 대하여서도 더욱 硏究할 필요가 있다. In order to study the effects of the water extract of Gagaminjinhotang in the Meridian points Liv 14 on the liver damage indued by bile duct ligation during 7 weeks after the operation of bile duct ligation, blood was taken from the heart and body weight, WBC, RBC, hemoglobin, hematocrit, total bilirubin, ALT, AST, ALP, cholesterol, albumin and hydroxyproline were in each experimental apparatus. The results of this study were as follows; 1. Body weight of EXA, C were significantly increased by the water extract of Gagaminjinhotang. 2. WBC of EXA,B,C were significantly decreased by the water extract of Gagaminjinhotang. 3. RBC, hemoglobin and hematocrit of EXA,B,C were not significantly influenced by the water extract of Gagaminjinhotang. 4. Total bilirubin of EXA,C and direct bilirubin of EXA,B,C were significantly decreased by the water extract of Gagaminjinhotang. 5. ALT, AST,ALP of EXA,B,C were significantly decreased by the water extract of Gagaminjinhotang. 6. Cholesterol of EXA,B,C, were significantly decreased by the water extract of Gagaminjinhotang. 7. Albumin of EXA,B,C, were significantly increased by the water extract Gagaminjinhotang. 8. Hydroxyproline of EXA,B were significantly decreased by the water extract Gagaminjinhtang. 9. On the histological observation, the results of the experimental groups showed significant hepatoprotective effects compared with control group from 3 weeks after the administration of the water extract of Gagaminjinhotang. According to the above result, it is suggested that the water extract Gagaminjinhotang was significantly effective in WBC, bilirubin, ALT, AST, ALP, cholesterol, albumin and hydroxyproline level and then it seems to be applicable to the fibrosis or cirrhosis of liver.

獨活寄生湯이 galactosamine에 의한 白鼠의 肝損傷誘發에 미치는 影響

朴元煥 대한동의병리학회 1997 동의생리병리학회지 Vol.11 No.2

肝疾患에 대한 診斷과 기술의 발전에도 불구하고 예방과 치료방법론에 있어서 어려움을 겪고 있다. 臨床的으로 널리 이용되고 있는 藥物의 毒性有無와 약물의 效能을 立證하기 위하여 실험적으로 약물투여가 肝損傷에 어떻게 작용하는지를 객관화하려는 연구가 여러 방면에서 활발히 진행되고 있다. 한의학계에서도 오랫동안 간손상과 관련된 실험적 효능 연구가 지속되어 다양한 연구자료가 있는 실정이다. 본 실험은 galactosamine에 의해 유발된 간기능손상에 독활기생탕이 미치는 영향에 관한 실험적 보고이다. 肝장애를 일으키는 작용을 하는 약물인 galactosamine을 이용하여 간손상을 일으켰으며, 독활기생탕은 galactosamin투여 전후에 각각 공급하였다. 즉, 獨活寄生湯 蒸湯液이 galactosamine으로 誘導된 肝中毒에 미치는 영향과 獨活寄生湯 煎湯液이 체내 정상간대사에 미치는 영향을 관찰하고자 獨活寄生湯 煎湯液을 각각 흰쥐에게 전처치하고 galactosamine으로 肝毒性을 유발 시키면서 계속 獨活寄生湯煎湯液을 공급시킨 후 血淸中의 GOT, GPT, r-GTP, ALP, LDH, total bilirubin의 활성을 측정 비교하였던 바 유의한 결과를 얻었다. The purpose of this study is to observe the effect of Dokhwalgisangtang aqueous solution on serum reaction in galactosamine treated rats. In this study the experimental rats divided five groups (Normal group, Control group, Sample 1, 2, 3 groups). Under the same condition, normal group was administered water, control group was treated galactosamine. sample 1 group was administered the Dokhwalgisangtang aqueous solution(200㎖/㎏ p.o) for 8 days and injected galactosamine (800㎖/㎏ i. p) for the last day. Then, rats were neglected for 8 days. Sample 2 group was treated as same as group A for the first 8 days. After then, rats were administered the Dokhwalgisangtang aqueous solution for further 8 days. Sample 3 group was administered the Dokhwalgisangtang aqueous solution (200㎖/㎏ p.o) for 16 days and were not injected galactosamine. The change of GOT GPT γ-GTP ALP LDH activity in blood serum. The obtained results are summarised as follows : 1. In the change of GOT GPT contents, as compared with control group, sample 1, 2 groups were significantly decreased. 2. In the change of γ-GTP contents, as compared with control group, sample 2 group was significantly decreased. 3. In the change of ALP contents, as compared with control group, sample 2 groups was significantly decreased. 4. In the change of LDH contents, as compared with control group, sample 1, 2 groups were significantly decreased. 5. In the change of total bilirubin contents, as compared with control group, sample 1, 2 groups were significantly decreased.

보중익기탕합인진사령산이 CCl₄中毒 흰쥐의 肝損傷에 미치는 影響

河智容,白泰鉉,張梗植 대한동의병리학회 1997 동의생리병리학회지 Vol.11 No.1

간병변은 현대인들의 스트레스, 과로, 음주, 고지방식의 과다 섭취 등의 각종 원인에 의하여 점차 증가하고 있는 실정이다. 최근 이에 따라 간기능을 보조하는 드링크류나 약재가 개발되어 시판되고 있으나, 아직까지 뚜렷한 효능을 가진 약재가 없는 현실이다. 간질환이 발병시 피로, 노권, 식용부진, 황달, 복수, 발열, 심와부통(心窩部痛), 구토, 소변황적 등의 증상을 호소하는데 이를 변증하여 보면 허중협실(虛中狹實) 즉 허증인 중기부족증(中氣不足症)과 실증인 비위습열증(碑胃濕熱症)이 혼재되어 있음을 알수 있다. 이에 본 저자는 부정거사(扶正祛邪)가 간질환 치료에 효과적일 것으로 보고 보중익기탕(補中益氣湯)과 인진사령산(茵蔯四笭散)을 합방하여 CCI₄로 간손상을 유발한 백서(白鼠)의 투여하여 간기능회복여부를 연구하고자 하였다. 군을 정상군, CCI₄처리군, CCI₄처리후약재투여 A군(10㎎/㎏), CCI₄처리후약재투여 B군(20㎎/㎏)으로 나누어 일정기간 약재를 투여한후 채혈하여 AST, ALT, Bilirubin, ALP, γ-GT, LDH, Albumin, total cholesterol, α-Fetoprotein의 함량을 측정하였다. AST, γ-GT, α-Fetoprotein의 경우는 A, B군에서 대조군에 비하여 감소하였으나 A군에서는 유의성이 인정되지 않았고, ALT의 경우는 A, B군 모두에서 유의성있는 감소를 보였으며, Bilirubin의 경우 A, B군 모두 대조군에 비하여 증가하는 경향을 보였으며, ALP의 경우 A군에서는 감소하였으나 B군의 경우 오히려 증가하는 경향을 보였다. LDH의 경우 A, B군 모두 감소하였으나 유의성은 나타나지 않았으며 Albumin의 경우 A, B 모두 증가하는 경향은 보였으나 유의성은 없었다. total cholesterol의 경우 A, B군 모두 유의성있는 증가를 보였다. 이상의 결과를 종합하여 볼 경우 보중익기탕합인진사령산(補中益氣湯合茵蔯四笭散)은 간손상 회복에 영향을 미치는 것으로 보여지며 회복기전에 관련된 연구는 더욱 진행되어야 할것으로 보여진다. This paper is to investigate what effects Bojungikkitanghapinjinsaryungsan-treated A-group(10㎎/㎏ treated group) and Bojungikkitang-hapinjinsaryungsan-treated B-group(20㎎/㎏ treated group) have on ratliver injured by Ccl₄, So this experimental research is focused on measuring about AST, ALT, bilirubin, ALP,γ-GT, LDH, albumin, TP, and α-Fetoprotein. The results are summarized as follow; 1. As to AST(GOT), Bojungikkitanghapinjinsaryungsan-treated A-group was slightly decreased with no effectiveness, but Bojungikkitan-ghapin-jinsaryungsan-treated B-group was decreased with effectiveness, as compared with the control group. 2. As to ALT(GPT) Bojungikkitanghapinjinsaryungsan-treated A-group and Bojungikkitanghapinjinsaryungsan-treated B-group were decreased with effectiveness, as compared with the control group. 3. As to bilirubin, Bojungikkitanghapinjinsaryungsan-treated A-group Bojungikkitanghapinjinsaryungsan-treated B-group were increased, as compared with the control group. 4. As to ALP, Bojungikkitanghapinjinsaryungsan-treated A-group was slightly decreased with no effectiveness, but Bojungikkitanghapinjinsaryungsan-treated B-group was slightly increased. 5. As to γ-GT, Bojungikkitanghapinjinsaryungsan-treated A-group was slightly decreased with no effectiveness, but Bojungikkitanghapinjinsaryungsan-treated B-group was decreased with effectiveness, as compared with the control group. 6. As to LDH, Bojungikkitanghapinjinsaryungsan-treated A-group and Bojungikkitanghapinjinsaryungsan-treated B-group were slightly decreased with no effectiveness, as compared with the control group. 7. As to albumin, Bojungikkitanghapinjinsaryungsan-treated A-group and Bojungikkitanghapinjinsaryungsan-treated B-group were slightly increased with no effectiveness, as compared with the control group. 8. As to TP, Bojungikkitanghapinjinsaryungsan-treated A-group and Bojungikkitanghapinjinsaryungsan-treated B-group were increased with effectiveness, as compared with the control group. 9. As to α-Fetoprotein, Bojungikkitanghapinjinsaryungsan-treated A-group was slightly decreased with no effectiveness, but Bojungikkitanghapinjinsaryungsan-treated B-group was decreased with effectiveness, as compared with the control group. According to the above result, it could be suggested that Bojungikkitanghapinjinsaryungsan have prominent improvement on the liver disease.

Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

박효민,이동원,현명철,이상범 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.2

Purpose: It has been reported that 10% to 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. Methods: We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. Results: Among the 309 children, 30 (9.7%) did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT), total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or,clinical features were noted. Conclusion: Two independent predictors (ALT≥84 IU/L, total bilirubin≥0.9 mg/dL) for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

Park, Hyo Min,Lee, Dong Won,Hyun, Myung Chul,Lee, Sang Bum The Korean Pediatric Society 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.2

Purpose: It has been reported that 10% to 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. Methods: We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. Results: Among the 309 children, 30 (9.7%) did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT), total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIG-nonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. Conclusion: Two independent predictors (ALT${\geq}$84 IU/L, total bilirubin${\geq}$0.9 mg/dL) for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

Genetic Polymorphisms of UGT1A and their Association with Clinical Factors in Healthy Koreans

Kim, Jeong-Oh,Shin, Jeong-Young,Lee, Myung-Ah,Chae, Hyun-Suk,Lee, Chul-Ho,Roh, Jae-Sook,Jin, Sun-Kyung,Kang, Tae-Sun,Choi, Jung-Ran,Kang, Jin-Hyoung Korea Genome Organization 2007 Genomics & informatics Vol.5 No.4

Glucuronidation by the uridine diphosphateglucuronosy-ltransferase 1A enzymes (UGT1As) is a major pathway for elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 $(TA)_{6>7}$, 211G>A, and 686C>A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 $(T)_{9>10}$ of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 $(TA)_{6>7}$ polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 $(T)_{9>10}$ rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.

건강한 한국인 성인 남자에서 혈중 총 빌리루빈 농도와 Framingham 위험 점수와의 관계

전혜진,이상화,최유경,이홍수,심경원 대한임상건강증진학회 2013 Korean Journal of Health Promotion Vol.13 No.1

Background: Serum total bilirubin has been considered a harmful substance inducing oxidative reaction; but recently,there have been reports of it possessing antioxidative, anti-inflammatory and protective features against cardiovascular diseases. The purpose of this study was to investigate the relationship between total bilirubin and the Framingham risk score. Methods: This study involved 3,414 healthy Korean men who underwent a medical check-up in a health promotion center in 2008. We calculated the Framingham risk score using age, smoking status, systolic blood pressure,total cholesterol and high-density lipoprotein cholesterol. Results: The mean age of the participants was 44.9±8.8 years. The log transformed serum total bilirubin level and the Framingham risk score had a negative linear relationship in a simple linear regression analysis (R2:0.018, P<0.001). In a multivariable analysis model, as well, the log transformed serum total bilirubin level and the Framingham risk score had a negative linear relationship (R2: 0.384, P<0.001). Conclusions: Our study showed a statistically significant negative relationship between total bilirubin and the Framingham risk score. Total bilirubin had a stronger relationship with the Framingham risk score than other standard cardiovascular risk factors except smoking, and thus may be useful in predicting cardiovascular risk in the outpatient clinic. 배경: 총 빌리루빈은 산화작용을 하는 해로운 물질로 생각되어 왔으나 최근 항산화, 항염증 효과 및 과산화기 제거기능이 밝혀지면서 심혈관계 보호인자로서 주목을 받고있다. Framingham 위험점수는 20-79세 성인에서 향후 10년간 관상동맥 심혈관 질환의 위험도를 평가할 수 있는 점수로 본 연구는 총 빌리루빈과 Framingham 위험 점수와의관계를 밝히고자 한다. 방법: 검진센터의 검진자 중 심혈관계 질환이 없는 성인남자 3,414명을 대상으로 연령, 흡연, 수축기 혈압, 총 콜레스테롤, 고밀도 지단백 콜레스테롤을 점수화하여 Framingham 위험점수를 계산하였다. 로그 치환한 총 빌리루빈과 Framingham 위험점수와의 관계는 단순선형회귀분석을 시행하여 분석하였고 이후 다중선형회귀분석을 시행하였다. 결과: 로그치환 혈중 총 빌리루빈과 Framingham 위험점수는 단순선형회귀분석 결과 음의 상관관계를 보였고(R2:0.018, P<0.001) 이완기 혈압, 맥박수, 체질량 지수, 공복혈당,중성지방, 저밀도 콜레스테롤, aspartate aminotransferase,alanine aminotransferase, 흡연 유무를 통제한 후 분석한 다중선형회귀분석 결과 음의 상관관계를 보였다(R2: 0.384, P <0.001). 결론: 총 빌리루빈 수치와 Framingham 위험점수와의음의 상관관계가 있음을 확인하였고 이는 총 빌리루빈 수치가 심혈관계 질환의 독립적인 위험인자이며 심혈관계위험도를 예측하는 유용한 인자로 활용될 수 있음을 의미한다.

혈청 빌리루빈치의 관상동맥심질환 위험도와의 연관성

윤혜령,김진주 대한임상병리학회 1997 대한임상병리학회지 Vol.17 No.4

Bilirubin Oxidase 법에 의한 혈청 벌리루변 측정법의 고찰

양석환 ( S H Yang ) 대한임상검사과학회 1992 대한임상검사과학회지(KJCLS) Vol.24 No.1

A new method currently used for measuring bilirubin are the enzymatic assay by bilirubin oxidase. The purpose of this study was to investigate that enzymetic method with Jendrassik-Grof``s method. The results were as follows : 1. Concentration linearity for standard and pooled serum was excellent. Total bilirubin and direct bilirubin showed linearity up to concentrations of at least 20.7 mg/dl and 9.2 mg/ dl respectively. 2. The degree of within-run precision was good. 3. Correlation with Jendrassik-Grof``s method was total bilirubin 0.9923, direct bilirubin 0.9797. This correlation is very excellent. 4. No apparent interference was noted of hemolysis and lipemic. This method is simple and precise and the application for use with automated analyzers is now under investigation.

신생아의 TPN 요법 시 발생되는 Cholestasis 치료를 위한 Ursodeoxycholic Acid의 약물사용 평가

이정옥(Jung Ok Lee),송태범(Tae Beom Song),이명구(Myung Koo Lee),임성실(Sung Cil Lim) 대한약학회 2010 약학회지 Vol.54 No.4

Total parenteral nutrition (TPN) is necessary to neonates in neonatal intensive care unit (NICU) for survival and growth because of impossible of enteral feeding. Long-term TPN can be associated with a broad spectrum of hepatobiliary disorder, ranging from mild hepatic dysfunction to severe end-stage liver disease. Cholestasis developed most commonly in neonate, ursodeoxycholic acid (UDCA) is widely used in adult with cholestatic and non-cholestatic liver diseases but there have been limited data on the effects in neonate with PNAC. This study was performed retrospectively to review all medical histories of the total 30 neonates with was administrated UDCA for treatment to parenteral nutrition associated cholestasis (PNAC) at Chungbuk National University Hospital NICU from April 2002 to December 2008. UDCA was administrated at bilirubin is over 2 mg/dl. The criterias for drug evaluation were included hepatic biochemical marker such as direct bilirubin, total bilirubin, AST, ALT, ALP and GGT, TPN therapy period, cholestasis development period, UDCA treatment period, UDCA dosage and adverse effect. In the results, Post-UDCA treatment significant was decreased direct bilirubin, total bilirubin, AST and ALP (p<0.05), and was decreased GGT (p>0.05) and slightly was increased ALT (p>0.05). Reffective timect biDCA was appear at mean 10.5±1.3 days, iDCA administration period was mean 64.4±5.9 days, cholestasis period was mean 71.9±6.4 days and UDCA dosage was mean 22.9±0.9 mg/kg/day. Common adverse effects is diarrhea, 5 patients arised mild diarrhea but it possible also related with increased enteral feeding. In conclusion, iDCA can decrease direct bilirubin that major parameter t bcholestasis and oher hepatic biochemical makers. UDCA is effective on PNAC without any serious side effect and cost-effective. Although no greatly shortening cholestasis period, but can protect to develop into severe liver disease and other complication or death. Based on these result, UDCA is recommended for treatment of cholestasis at direct bilirubin is over 2 mg/dl.