• 제목/요약/키워드: Hepatic

검색결과 3,795건 처리시간 0.031초

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced Colorectal Cancer

  • Huang, Xin-En;Yan, Xiao-Chun;Wang, Lin;Ji, Zhu-Qing;Li, Li;Liu, Meng-Yan;Qian, Ting;Shen, Hui-Ling;Gu, Han-Gang;Liu, Yong;Gu, Ming;Deng, Li-Chun
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권17호
    • /
    • pp.7867-7869
    • /
    • 2015
  • Objective: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. Method: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. Results: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41-82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Conclusions: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권12호
    • /
    • pp.5917-5935
    • /
    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

장기 고온 스트레스에 대한 미꾸라지(Misgurnus mizolepis) 간 조직 내 유전자 발현 반응의 cDNA microarray 분석 (Survey of Genes Responsive to Long-Term Heat Stress Using a cDNA Microarray Analysis in Mud Loach (Misgurnus mizolepis) Liver)

  • 조영선;이상윤;노충환;남윤권;김동수
    • 한국어류학회지
    • /
    • 제18권2호
    • /
    • pp.65-77
    • /
    • 2006
  • 우리나라 주요 담수 어종인 미꾸라지(Misgurnus mizolepis)를 실험 모델로 이용하여 실험적으로 설정한 고온 노출($32^{\circ}C$)에 특이적으로 반응하는 유전자들을 cDNA microarray 분석을 통해 탐색하였다. 미꾸라지 간조직 expressed sequence tag (EST) 데이터베이스 분석을 통해 1,124개의 unigene들을 선발하여 제작한 cDNA microarray을 이용하여 $23^{\circ}C$$32^{\circ}C$에 4주간 노출된 실험어의 간(liver)조직의 전사 발현 양상을 3반복 분석하였다. 다양한 유전자군이 $32^{\circ}C$ 고온 노출에 전사 발현의 증감 또는 감소 양상을 보였으며 $23^{\circ}C$에 비해 $32^{\circ}C$군에서 2배 이상의 발현 증가를 보인 클론들은 총 93종류로서 에너지 대사, 단백질 대사, 면역/항산화 기능, 세포골격 및 구조, 물질수송 및 세포 신호전달등에 관여하는 단백질들을 암호화하는 유전자들이었고 최대 15배 이상의 전사발현이 관찰되었다. 반면 고온 노출군에서 유의적인 발현 감소(50% 이하)를 보인 유전자들(n=85) 역시 탐색되어 상기 단백질 분류군외에 vitellogenin 전구체들 및 리보좀 단백질류에서 특이적인 전사활성의 저하가 관찰되었고, vitellogenin 유전자에서 가장 많은 mRNA 수준의 감소가 관찰되었다.

골담초 열수 추출물의 갱년기 이후 지질 및 당질 대사 개선 효능 (Effects of a Caragana sinica Water Extract on Lipid and Glucose Metabolism in Ovariectomized Rats)

  • 이상철;정수임;강미영
    • 한국자원식물학회지
    • /
    • 제29권5호
    • /
    • pp.532-538
    • /
    • 2016
  • 난소의 노화에 의해 폐경이 시작되면 에스트로겐 분비가 중단되어 여러 폐경 증상들을 겪게 되는데 이것으로 인해 발병되는 성인병 질환에 대한 치료 또는 예방에 대한 연구가 활발히 진행되고 있다. 본 연구의 목적은 난소절제술을 통해 폐경을 유도한 흰 쥐 모델에서 골담초 열수 추출물의 체내 물질 대사 관련 여부 및 개선 효과를 검토하기 위하여 실험을 수행하였다. Sprague-Dawley 암컷 쥐30마리를 비절제난소군(SHAM), 난소제거군(OVX) 그리고 골담초 추출물을 급여한 OVX-CS군으로 각각 10리씩 나누어 8주간 사육하였다. 체중 및 체중증가량 그리고 지방조직무게는 OVX군에서 유의적으로 증가하였으며 OVX-CS 군에서 감소하였다. 에스트로겐 결핍으로 인한 혈장 중성지질, 총콜레스테롤 수준은 골담초 추출물 급여에 따라 감소하고 HDL 콜레스테롤 수준은 증가하였다. 또한 지방산 합성 관련 효소 활성도인 ME는 간조직에서는 OVX-CS군에서 유의적으로 감소하였고 G6PD 활성은 OVX 군들 간에는 차이가 없었다. 당신생합성 관련 효소인 G6pase 활성은 골담초 추출물 섭취에 따라 억제되는 것으로 나타났다. 혈장 아디포카인 측정 결과 렙틴 농도는 OVX-CS군이 정상군 수치만큼 감소하였으며, 아디포넥틴도 정상수준으로 증가하였다. 이상의 결과로 난소제거를 통해 폐경이 유도된 흰쥐모델에서 골담초 추출물 급여가 에스트로겐 결핍으로 인한 체중증가를 억제하고, 지질 및 당질 대사에 긍정적인 영향을 미쳐 건강기능성 소재로서의 가능성이 높은 것으로 보이며, 추후 골담초의 구체적인 생활성물질을 추적하여 그 과학적 기전을 밝히는 것이 필요하다고 판단된다.

인터루킨-2의 제제설계를 위한 체내 동태학적 연구 (Pharmacokinetic Preformulation Study of rH IL-2)

  • 서민석;심창구;권종범;나도선;이선복;함경수;한문희
    • 약학회지
    • /
    • 제34권4호
    • /
    • pp.238-243
    • /
    • 1990
  • Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

  • PDF

비타민 A 및 피리딘으로 유발된 사염화탄소 유발성 간독성에 대한 2-(알릴티오)피라진의 보호효과: ${\Phi}$x-174 DNA 손상에 미치는 효과 (Protective Effects of 2-(Allylthio)pyrazine on Retinoyl Palmitate- and Pyridine-Potentiated Carbon tetrachloride- induced Hepatotoxicity: Effect on ${\Phi}x$-174 DNA Strand Breakage)

  • 김상건;조주연;최성희;김낙두
    • 약학회지
    • /
    • 제40권6호
    • /
    • pp.727-733
    • /
    • 1996
  • 2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiat ed chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl$_4$ resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled ${\Phi}x$-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5 ${\mu}$M benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220 ${\mu}$M, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850 ${\mu}$M), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl$_4$ hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

  • PDF

바닷물과 조개에서 패혈증비브리오균 증식에 대한 천연물의 항균 효과 (Antibacterial effects of natural products on Vibrio vulnificus growth in seawater and shellfish)

  • 홍영진;류필열;김승용;염경민;박정업;조세진;궈루이홍;트란더베치;진항;김영란
    • 한국식품과학회지
    • /
    • 제52권1호
    • /
    • pp.89-93
    • /
    • 2020
  • 본 연구에서는 패혈증비브리오균에 대한 PEM, RCM, RRM과 CTM 메탄올 추출물의 항균 활성을 평가하였다. 96-well microplates를 사용한 액체 배양법 실험 결과 4가지 천연물은 200 ㎍/mL 농도에서 80%이상의 항균 효과를 나타내었다. 또한 페이퍼디스크 확산법을 사용하여 항균 활성을 평가한 결과 4가지 천연물은 20, 40 mg/disc의 농도에서 농도 의존적으로 패혈증비브리오균의 성장을 억제하였다. 다음으로 4가지 천연물의 안전성을 평가하기 위해 MTS assay를 통해 HeLa 세포에 대한 독성을 확인한 결과 100, 200 ㎍/mL의 농도에서 세포 독성을 나타내지 않았다. 또한 LDH assay를 사용하여 패혈증비브리오균의 HeLa 세포에 대한 세포막 손상 억제 효과를 평가한 결과 PEM, RCM, RRM과 CTM 메탄올 추출물은 200 ㎍/mL 농도에서 세포막 손상억제 효과를 나타내었다. 다음으로 바닷물과 조개를 사용한 수족관 모델에서 4가지 천연물의 메탄올 추출물 혼합액 200 ㎍/mL 농도는 colony 생성을 현저하게 감소시켜 패혈증비브리오균의 증식을 억제 하는 결과를 나타내었다. 이와 같은 결과를 통해 4가지 천연물의 메탄올 추출물은 바닷물과 해산물에 존재하는 패혈증비브리오균에 대해 뛰어난 항균효과를 나타내면서 인체에는 무해한 천연소독제로 응용할 수 있을 것으로 판단된다.

생약복합제제(生藥複合製劑)(사물청간장(四物淸肝腸))의 흰쥐 약물성(藥物性) 간(肝) 장해(障害)에 대한 보호작용(保護作用) (Protective Effects of a Composite Preparation (Samulchungkan-Tang) of Crude Drugs on Hepatic Injury Induced by Toxic Drugs in Rats)

  • 엄기진;정명현
    • 생약학회지
    • /
    • 제26권4호
    • /
    • pp.390-410
    • /
    • 1995
  • This study was attempted to investigate the effects of Composite Preparation (Samulchungkan-Tang) extract (SCTE), Scutellarias Radix extract (SRE), Artemisiae iwayomogii Herba extract (AIHE), Artemisia capillaris Flos extract (ACFE), Paeaniae Radix extract (PRE) and Gardeniae Fructus extract (GFE) on the activities of GOT, GPT, ALP and LDH, and Content of total cholesterol in serum of $CCl_4$ and ${_D}-galactosamime$ intoxicated rats, and bile flow in rats. 1) In $CCl_4-intoxicated$ rats-The activities of S-GOT and S-GPT which were elevated by $CCl_4$ were significantly decreased in dose of SCTE 450 mg/kg, ACFE 600 mg/kg and GFE 300 mg/kg, respectively as compared to $CCl_4$ intoxicated rats. ALP activity increased by $CC1_4-treatment$ was markedly decreased in dose of SCTE 450 mg and 600 mg/kg, SRE 400 mg/kg, AIHE 400 mg/kg, ACFE 600 mg/kg and PRE 300 mg/kg, and LDH activity in SCTE 450 mg and 600 mg/kg, ACFE 600 mg/kg and GFE 300 mg/kg, respectively compared to $CCl_4$ treated rates. ACFE 400 mg/kg and PRE 300 mg/kg decreased the content of total cholesterol increased by $CCl_4$, the liver weight in all sample administered groups was decreased significantly as compared to $CCl_4$ treated groups. 2) In ${_D}-galactosamine$ intoxicated rats-Sample of SCTE 450 mg and 600 mg/kg, SRE 400 mg/kg, AIHF 400 mg and 600 mg/kg, ACFE 600 mg/kg, PRE 300 mg/kg and GFE 300 mg and 500 mg/kg decreased the activities of S-GPT, ALP and LDH which was increased by ${_D}-galactosamine$ intoxication, compared to ${_D}-galactosamine$ intoxicated groups. In S-GOT activity elevated by ${_D}-galactosamine$ was significantly decreased by SCTE 450 mg/kg, ACFE 600mg/kg, AIHE 600 mg/kg, PRE 300 mg/kg, GFE 300 mg and 500 mg/kg. However, SCTE 600 mg/kg, SRE 400 mg/kg, and AIHE 400 mg/kg were not effected significantly. 3) In bile secretion-SCTE 450 mg and 600 mg/kg, ACFE 600 mg/kg and GFE 500mg/kg increased significantly the amount of bile secretion as compared to normal groups, but AIHE 400 mg/kg, SRE 400 mg/kg, and PRE 300 mg/kg did not effected significantiy.

  • PDF

흰쥐에 있어서 사염화탄소에 의한 간 손상이 toluene 대사에 미치는 영향 (Effect of CCl4-induced liver damage on the metabolism of toluene in rats)

  • 최우창;차상은;윤종국
    • 한국산업보건학회지
    • /
    • 제7권1호
    • /
    • pp.61-69
    • /
    • 1997
  • 흰쥐에 있어서 사염화탄소에 의한 간손상이 toluene 대사에 어떠한 영향을 미치는지를 알아보기 위하여 흰쥐에 $CCl_4$를 투여한 후 간기능 검사와 병리 조직 검사를 통하여 간손상이 확인되었다. 이같은 간손상 모델 실험동물에 toluene을 투여한 뒤 24시간 후 처치한 다음 요 중 hippuric acid 함량을 측정한 결과, 간손상이 유도된 후 흰쥐에 toluene을 투여한 실험군에 있어서 요 중 hippuric acid 함량이 toluene만 투여한 군 보다 현저히 감소되었다. 이때 toluene 대사에 관여하는 간조직의 cytochrome P-450에 상응하는 aniline hydroxylase 및 aminopyrine demethylase 활성과 benzylalcoh이 및 benzaldehyde dehydrogenase 활성 역시 간손상이 유도된 흰쥐에 있어서 유의하게 감소되었다. 또한 benzaldehyde dehydrogenase 활성의 kinetics를 관찰한 결과, 간손상이 유도된 실험동물 및 대조군 모두 유사한 $K_m$치를 보였으나 $V_{max}$치는 간손상이 유도된 실험동물에서 낮게 나타났다. 이상 실험결과를 종합하여 볼 때 $CCl_4$에 의한 간손상시 toluene 대사가 억제되며 이는 toluene 대사에 관여하는 효소단백합성 억제에 기인된 결과로 사료된다.

  • PDF

초음파추출과 열수추출에 의한 민들레의 항산화 및 지질강하 효과 (Effects of Dandelion (Teraxacum platycarpum) with Various Extracting Method on Antioxidative Capacity, Lipid Metabolism in Diet-induced Obese Rats)

  • 양하영;이선구
    • 동의생리병리학회지
    • /
    • 제25권1호
    • /
    • pp.48-54
    • /
    • 2011
  • This study was conducted to investigate the effects of dandelion (Teraxacum platycarpum) extracts obtained by only water and with ultrasonification on antioxidative system and lipid metabolism in high cholesterol-fed rats. Five groups of rats were given high cholesterol diets for 8 weeks. The control group received without dandelion extracts and the other four groups received with one of dandelion extracts for 4 weeks respectively ; TP-N-1(100 mg/kg/day of Teraxacum platycarpum water extract), TP-N-2(200 mg/kg/day of Teraxacum platycarpum water extract), TP-S-1(100 mg/kg/day of Teraxacum platycarpum water-ultrasonification extract), TP-S-2(200 mg/kg/day of Teraxacum platycarpum water-ultrasonification extract). The results are summarized as follows; The hepatic and plasma TBARS levels significantly decreased in the dandelion extracts groups compared to those of no treatment group. Especially the group TP-N-2 was comparatively best among those. TP-N-2 groups had significantly higher levels of glutathione peroxidase (GSH-Px) and catalase activities. There was no significant difference between dandelion extracts groups and no treatment group in SOD levels. In plasma triglyceride level, plasma FFA level, TP-S-2 group had significantly lower levels than that of the other groups. In plasma glucose levels, dandelion extracts group were similar to those of normal rats. Plasma total cholesterol levels significantly decreased in the TP-S-2 group compared to those of the other groups. HDL levels were also significantly higher than those of the other groups. Compared with those of no treatment group, dandelion extract groups had significantly higher levels of LDL. In liver total cholesterol level, TP-S-2 groups had significantly lower levels than that of the other groups. Compared with those of no treatment group, dandelion extracts groups had significantly lower levels of liver triglyceride, but especially the TP-S-2 group showed comparatively the best significant effect among those. TBARS, triglyceride, LDL, FFA levels significantly decreased in TP-S-2 groups compared to the other four groups. HDL levels was also significantly higher than the other four groups. According to the above result, it could be suggested that ultrasonic extraction have the upper hand in lipid metabolism and water extraction have the advantage of antioxidative system.