• Molecules and Cells
• /
• 제37권1호
• /
• pp.66-73
• /
• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• 대한본초학회지
• /
• 제33권1호
• /
• pp.37-46
• /
• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제2권2호
• /
• pp.169-177
• /
• 1999

목 적: 소아 만성 B형 간염 환아에서 알파 인터페론의 치료 효과는 보고자마다 차이가 있으나 30~40%로 알려져 있다. 그러나 만성 지속성 B형 간염, 혈청 ALT치가 낮은 경우나 혈청 HBV DNA치가 높은 소아 만성 B형 간염 환자에서 알파 인터페론 단독 투여 시 그 치료 효과는 더 낮다고 보고되고 있다. 이에 저자들은 알파 인터페론 단독 투여 시 치료 효과가 낮다고 알려진 소아 만성 B형간염 환자에 prednisolone 이탈 요법 후 인터페론 병용 투여 시 그 치료 효과를 알아보고자 본 연구를 시행하였다. 대상 및 방법: 1996년 1월부터 1997년 12월까지 전남대학교병원 소아과에 내원하여 만성 B형 간염으로 진단받은 28명을 대상으로 하였다. 대상 환아 중 간 조직 검사 상 만성 활동성 간염을 보이고 혈청 ALT치가 100 IU/L 이상이고 혈청 HBV-DNA치가 100 pg/$300\;{\mu}L$ 미만인 14명(group 1)은 알파 인터페론을 체표면적($m^2$) 당 5백만 단위를 6개월 동안 주 3회 단독 투여하였다. 조직 검사 상 만성 지속성 간염인 경우와 만성 활동성 간염이면서 혈청ALT치가 100 IU/L 미만 또는 혈청 HBV DNA치가 100 pg/$300\;{\mu}L$ 초과한 14명(group 2)은 prednisolone을 60 mg/$m^2$, 40 mg/$m^2$, 20 mg/$m^2$으로 각각 2주씩 6주간 경구 투여하고 2주간 휴약 기간을 가진 후 알파 인터페론을 group 1과 같은 방법으로 투여하였다. 치료에 대한 반응은 인터페론 투여가 종료되는 시점에서 완전반응(항 HBe 항체의 양전화, 혈청 ALT 정상화 및 혈청 HBV-DNA 음성), 부분반응(혈청 ALT 정상화 또는 혈청 HBV-DNA 음성) 및 무반응으로 평가하였다. 결 과: 1) 대상 환아의 평균 연령은 130.6개월(21~192개월)이었고, 남아는 22례, 여아는 6례이었다. 만성 지속성 간염은 11례, 만성 활동성 간염은 17례이었고, 15명의 환아에서 모친이 B형 간염 바이러스 만성 보유자이었다. 2) Group 1에서 평균 연령은 144.1개월(97~169개월), 남아 9명, 여아 5명, 혈청 ALT $299.9{\pm}215.3$ IU/L, HBV-DNA $49.3{\pm}33.1\;pg/300\;{\mu}L$이었고, group 2에서 평균 연령은 112.1개월(21~192개월), 남아 13명, 여아 1명, 만성 지속성 간염 11명, 만성 활동성 간염 3명, 혈청 ALT $85.6{\pm}71.0$ IU/L, HBVDNA $524.3{\pm}1064\;pg/300\;{\mu}L$이었다. 3) Group 1에서 항 HBe 항체 양전은 10례(71.4%) 에서, 혈청 ALT는 9례(64.3%)에서 정상화되었고, HBV-DNA는 11례(78.6%)에서 음성화되었다. Group 2에서 항 HBe 항체 양전은 7례(50.0%)에서, 비정상 수치를 보인 9명의 환아 중 5명(55.6%)이 ALT 의 정상화를 보였고, HBV-DNA는 9례(64.3%)에서 음성화되었다. 두 군간의 항 HBe 항체의 양전율, ALT치의 정상화율, HBV DNA치의 음성화율에 있어서 통계학적으로 유의한 차이는 없었다. 4) Group 1에서 완전반응은 8례(57.1%), 부분반응은 3례(21.4%), 무반응은 3례(21.4%)이었고, group 2 에서는 완전반응 7례(50.0%), 부분반응 2례(14.3%), 무반응 5례(35.7%)으로 두 군간의 통계학적 유의한 차이는 없었다. 결 론: 소아 만성 B형 간염에 대한 치료로 인터페론 단독 요법으로 반응이 좋지 않을 것으로 예측되는 환자군에 스테로이드 이탈 요법 후 인터페론 병합 투여는 안전하고 효과적인 치료법으로 생각된다. 향후 치료 효과의 지속 여부에 대한 지속적인 관찰과 더 많은 환자를 대상으로 한 전향적인 비교 연구가 필요하리라 사료된다.

• 대한임상검사과학회지
• /
• 제40권2호
• /
• pp.86-93
• /
• 2008

This study was performed to investigation of the serum alpha-fetoprotein (AFP) levels in healthy adults. A total of 2,160 (male 1,415, female 745) health checkup adults were examined for AFP levels by chemiluminescence immunoassay (CLIA) method, during the period from September, 2007 to August, 2008. The mean serum AFP level was 2.168 (0.605~20.35) ng/mL, and it was 2.309 (0.605~20.35) ng/mL in male, 1.906 (0.605~10.36) ng/mL in female, respectively. 1,816 (male 1,109, female 709) healthy adults were screened for the absence of viral hepatitis and normal alanine amino transferase (ALT) levels. The mean serum AFP level of healthy adult was 2.041 (0.605~7.83) ng/mL, and it was 2.181 (0.605~7.83) ng/mL in male, 1.822 (0.605~6.55) ng/mL in female, respectively. Serum AFP increased with age group, there was a higher level in male compared to female. These results suggests that the use of reference value of AFP in healthy adults in the Jeonbuk. With the reference value now defined, it becomes possible to compare levels in different populations.

• 한국임상약학회지
• /
• 제7권1호
• /
• pp.22-32
• /
• 1997

The gastrointestinal disorders (GI disorders) is one of the most common diseases in Korea. The community pharmacists are often faced with the complaints of symptoms due to the GI disorders. However the drugs used to treat the GI disorders are frequently abused by the patients themselves because these drugs are easily available and have high placebo effects. Therefore, we have reviewed the digestive diseases statistics of 1996 to find out the frequencies of the GI disorders in the outpatients of Samsung Medical Center. Using these statistic data, we figured out the frequently diagnosed GI disorders and analysed commonly used prescriptions from February 1st to 28th of 1997. In addition, we also evaluated the commonly used drugs in these prescriptions. About twenty thousands of patients visited the hopital because of their GI symptoms in 1996. It was found that dyspepsia, viral hepatitis, and gastric and duodenal ulcer disease are frequently diagnosed in these patients. In a point of view on other GI disorders, gastritis and duodenitis, irritable bowel syndrome, gastroesophageal reflux disease, constipation and diarrhea were commonly detected. And a number of drugs were prescribed to treat the GI disorders, which included the prokinetics, Histamine-2 receptor antagonists, proton pump inhibitor, antacids, tranquillizers, antidepressants, antispasmodics, laxatives and so on. Interestingly, there were many prescriptions composing of the antibiotic regimens to eradicate H. pylori which has been proven to cause peptic ulcers.

• BMB Reports
• /
• 제33권2호
• /
• pp.126-132
• /
• 2000

The hepadnaviruses replicate their nucleic acid through a reverse transcription step. The MBP-fused HBV polymerase was expressed in E. coli and purified by using amylase affinity column chromatography. The purified protein represented DNA-dependent DNA polymerase activity. In this report, the MBP-HBV polymerase was shown to lack 3'$\rightarrow$5' exonuclease activity, like other retroviral RTs. The ratio of the insertion efficiency for the wrong versus right vase pairs indicates the misinsertion frequency (f). The nucleotide insertion fidelity (1/f), observed with the MBP-HBV polymerase and HIV-1 RT, was between 60 and 54,000, and between 50 and 73,000, respectively, showing that they are in close range. A relatively efficient nucleotide incorporation by the MBP-HBV polymerase was observed with a specificity of three groups: (1) A : T, T : A>C : G, G : C (matched pairs), (2) A : C, C : A>G: T, T : G (purine-pyrimidine and pyrimidine-purine mispairs), and (3) C : C, A : A, G : G, T : T>T : C, C : T>A : G, G : A (purine-purine or pyrimidine-pyrimidine mispairs), and their order is (1)>(2)>(3). The data from the nucleotide insertion fidelity by the MBP-HBV polymerase suggest that the HBV polymerase may be as error-prone as HIV-1 RT.

• 한국자기공명학회논문지
• /
• 제21권3호
• /
• pp.109-113
• /
• 2017

The hepatitis C virus (HCV) internal ribosome entry site (IRES) is an RNA structure located in the 5'-UTR of the HCV RNA genome. The HCV IRES consists of four domains I, II, III, and IV, where domains II - IV are recognized by 40S ribosomal subunit and the domain III is bound to eukaryotic initiation factor 3 (eIF3) for translation initiation. Here, we have characterized the tertiary interaction between an L-/K- rich peptide and the HCV IRES domain IV. To probe the peptide binding interface in RNA, we synthesized $^{13}C$- and $^{15}N$-double labeled RNA and the binding site was identified by using the chemical shift perturbation (CSP) NMR methods. Our results showed that the peptide binds to the upper stem of the IRES domain IV, indicating that the tertiary interaction between the IRES domain IV and the peptide would disrupt the initiation of translation of HCV mRNA by blocking the start codon exposure. This study will provide an insight into the new peptide-based anti-viral drug design targeting HCV IRES RNA.

• Journal of Ginseng Research
• /
• 제20권4호
• /
• pp.520-539
• /
• 1996

Based upon Shennong's Ancient Chinese Medical Textbook and Tsorngji Mingyi Byelu. Ginseng has been widely used for over 2,000 years in oriental countries. Scientific basic medical study or clinical study on ginseng was seal·toed 1910's in Eastern countries and from the 1950's in Western countries To obtain kotvledge of clinical studies on Korean ginseng. I investigated the following items 1) Oriental pharmacological documents. 2) the start and corrent state of ginseng research. 3) Clinical studies, 4) epidemiological studies. 5) non-medical human studies. 6) Foreign evaluation in published papers, and 7) future perspectives of clinical study. Although wide and profound research has been carried on the effect of ginseng (diabetes cardiovascular diseases, hypertension, liver diseases. gastrointestinal disorders soress, bram function. aging, antiradiation effect. anemia. hemopoiesis. immuomodulating effect. and tonic effect). Systemic clinical study to determine the therapeutic effects of speciblc disease have hardly been done even in other countries Clinical study or researches with human as the target. on ginseng has been performed in the field of body tenperazure. Pulse, clinical symptoms and hematological findings . fatigue, porformances. anemia. essential hypertension. blood sugar. serum cholesterol. lipid and prolactin. adrenocortical function. impotence. hypospermia. male sterility, climacteric disorder. anticancer effects. cancer preventive effects. and viral hepatitis. adverse effects. and prefered type of ginseng. At the same time as trying preventives or therapeutics from dietary oi natural products scientific research to support that ginseng is not a mystery. should be porformad to prove the effectiveness of Korean ginseng in the treatment of certain diseases using scientific methods or epidemiological approach.

• Archives of Pharmacal Research
• /
• 제19권6호
• /
• pp.486-489
• /
• 1996

A simple, rapid, specific and sensitive method for the detection of serum hepatitis C virus (HCV) RNA using the reverse transcription-polymerase chain reaction (RT-PCR) technique without conventional RNA extraction was developed. HCV template RNA from serum was obtained by boiling the serum at $95^{\circ}C$ for 2 min, cooling rapidly in ice and removing the proteins by cetrifugation. RT-PCR amplifications including the reverse transcription and first PCR amplification were performed in one vessel containing both of reverse transcriptase and Taq DNA polymerase. The detection of HCV RNA from $10^{-3}{\mu}l$. serum was possible with this method. The suitability of this method for clinical analysis was evaluated by assaying HCV RNA in 225 patient samples including anti-HCV antibody negatives (13 samples) and positives (212 samples) by enzyme-linked immunosorbent assay test (ELISA). Detections of HCV RNA with this method were in 4 of 13 anti-HCV antibody negative samples (30.8%) and 95 of 212 positive samples (44.8%). The present method can be completed in 1 hr and has a wide range of application for the clinical utilities to determine the viral RNAS.

• Journal of Yeungnam Medical Science
• /
• 제36권2호
• /
• pp.67-77
• /
• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.