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Combined Therapy of Alfa-Interferon and Thymodulin on Children with Chronic Active Hepatitis B (소아의 B형 만성 활동성 간염에서 저용량 ${\alpha}$-Interferon과 Thymodulin의 병용 치료 효과)

  • Choe, Byung-Ho;Ko, Cheol-Woo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.1 no.1
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    • pp.79-89
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    • 1998
  • Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

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The Comparison of Interferon-${\alpha}$ Treatment by Dosages and Retreatment for Chronic Hepatitis B in Children (소아 만성 B형 간염 환아에서 Interferon-${\alpha}$의 용량 차이 및 재치료에 따른 치료 효과 비교)

  • Jang, Chang-Hwan;Lee, Kyung-Hee;Hwang, Wi-Kyung;Oh, Ki-Won;Park, Woo-Saeng;Lee, Jun-Hwa;Ko, Cheol-Woo;Choe, Byung-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.6 no.2
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    • pp.152-160
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    • 2003
  • Purpose: We compared the therapeutic efficacy of low dose with that of standard dose of interferon (IFN) treatment and also compared the first IFN treatment with retreatment. Methods: We have studied 51 children (age, 2~14) treated for chronic hepatitis B from March 1990 to August 1999. Twenty seven children had been treated with $3\;MU/m^2$ ($2.66{\pm}0.66\;MU/m^2$) of IFN-${\alpha}$ three times a week for 6 months (range, 6~12 months), whereas 24 children with $6\;MU/m^2$ ($4.45{\pm}0.94\;MU/m^2$). There was no significant difference in gender, age, initial ALT and HBV DNA levels between each comparative group. Results: Among the 27 children treated with $3\;MU/m^2$ of IFN, ALT level had normalized in 11 children (41%) and anti-HBe seroconversion occurred in 9 children (33%) one year after the initiation of treatment. In comparison, among the 24 children treated with $6\;MU/m^2$ of IFN, ALT normalized in 12 children (50%) and anti-HBe seroconversion occurred in 7 children (29%). In comparing the first treatment group to retreatment group, ALT level had normalized in 23 children (45%) and anti-HBe seroconversion occurred in 16 children (31%) among the 51 children treated with the first course of IFN treatment. In comparison, ALT normalized and anti-HBe seroconversion occurred in 3 children (25%) among the retreated 12 children. Conclusion: There was no significant difference in the therapeutic efficacies between $3\;MU/m^2$ and $6\;MU/m^2$ dose of IFN treated groups in ALT normalization and anti-HBe seroconversion. The retreatment efficacy of IFN-${\alpha}$ was as effective as the first treatment.

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Serologic follow-up Study in neurocysticercosis patients by ELISA after praziquantel treatment (프라지콴텔 치료후 효소면역측정법에 의한 뇌 유구낭미충증 환자의 혈청학적 추적검사)

  • Cho, Seung-Yull;Kim, Suk-Il;Kang, Shin-Yong
    • Parasites, Hosts and Diseases
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    • v.24 no.2
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    • pp.159-170
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    • 1986
  • A total of 69 patients of confirmed neurocysticercosis was followed serologically by ELISA up to 22 months after praziquantel treatment. The intervals and numbers of follow-up were variable by patient. Serially collected samples of serum and CSF were examined simultaneously for their specific IgG antibody levels by ELISA, using cystic fluid, saline extracts of bladder wall and scolex as antigen. Within 4 months after praziquantel treatment, the antibody levels were elevated temporarily in both serum and CSF in most patients. In some cases antibody levels exhibited steady declining tendency after the treatment. Concomitant administration of dexamethasone appeared to suppress the elevation of antibody levels. The rate of mean absorbance of antibody changed more in serum than in CSF. The rate of elevation was greater in antibodies to parenchymal antigens than that to cystic fluid, but absolute difference of antibody levels was greater in antibody to cystic fluid. Previously negative samples for IgG antibody may become positive after the praziquantel treatment, which could be used as a complementary tool (provocation test) in serodiagnosis. One month was considered to be sufficient interval for the follow-up test for that purpose. In the follow-up of up to 22 months, only few cases of chronic neurocysticercosis showed declining tendency of IgG antibody levels below negative range. During acute encephalitic attacks in chronic patients, IgG antibody to parenchymal antigen were elevated in CSF temporarily. These results indicated that serologic follow-up of every year was recommendable to differentiate the cured patients from chronic patients with slowly calcifying lesions.

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Three Years' Cumulative Therapeutic Efficacy and Long-term Durability of Lamivudine in Korean Children with Chronic Hepatitis B (소아 만성 B형 간염에서 라미부딘 치료의 3년 누적 치료 반응과 장기 지속성)

  • Jang, You Cheol;Cho, Min Hyun;Choe, Byung-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.7 no.2
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    • pp.197-207
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    • 2004
  • Purpose: To evaluate the long-term therapeutic efficacy and durability of lamivudine in Korean children with chronic hepatitis B. Methods: A total of 48 children (31 male and 17 female; age, 1~18 years, mean, 8 years) with chronic hepatitis B who received lamivudine for at least six months from March 1999 to September 2004 were followed for a mean period of 29 months (8~66 months) at Department of Pediatrics, Kyungpook National University Hospital in Korea. Response to treatment was defined as the normalization of ALT and HBV DNA levels, and HBeAg seroconversion after the initiation of treatment. Results: Twenty nine (60%) among the 48 children treated with lamivudine responded and nine (19%) children lost HBsAg during therapy. ALT and HBV DNA level had normalized in 94% one year after the initiation of treatment. Kaplan-Meier estimates of cumulative HBeAg seroconversion rates over the years were 13% (0.5 year), 34% (1 year), 50% (1.5 years), 68% (2 years), 79% (2.5 years) and 90% at 3 years respectively. Above all, among the 22 children treated before the age of seven, loss of HBsAg occurred in eight (36%), which showed superior rate of HBsAg loss (p=0.002 vs age >7). Conclusion: Long-term treatment of lamivudine improved the rate of HBeAg seroconversion in Korean children with chronic hepatitis B. After three years' observation, most of treated children have sustained HBeAg clearance. We believe that lamivudine should be tried as the first therapeutic option for children with chronic hepatitis B in immune clearance phase.

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Monoclone 항체를 이용한 사람 EPO 형질전환돼지의 유즙내 발현단백질 분석

  • 이연근;정희경;이현기;이풍연;박진기;민관식;김진회;장원경
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.88-88
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    • 2002
  • Erythropoietin (EPO)는 조혈작용 (erythropoiesis)을 나타내는 호르몬으로서 사람의 빈혈치료제로 사용되며, 포유통물 중 사람, 생쥐 등의 유즙 내에 혈청 EPO 와 동일한 크기로 다량으로 존재한다고 보고된 바 있다. 생쥐의 WAP promoter를 이용하여 사람의 조혈촉진제인 EPO를 유즙으로 생산하는 형질전환돼지 (새롬이)의 유즙을 분석하기 위해 SDS-PAGE와 Western blotting 을 수행하였다. 먼저, 형질전환돼지의 유즙으로부터 원심분리에 의해 지방층을 제거한 후, 16.5% polyacrylamide gel 에서 PAGE를 수행하였다. (중략)

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The Development of Serum Free Medium for the Economic Production of scu-PA from HEK Cells (인간 신장세포로부터 scu-PA의 경제적 생산을 위한 무혈청 배지의 개발)

  • 김현규;김현구
    • KSBB Journal
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    • v.9 no.5
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    • pp.518-524
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    • 1994
  • Serum free medium was developed to cultivate Human Embryonic Kidney cells with Cytodex III microcarriers. The cells normally attached and spreaded on the microcarriers in serum free medium, and grew well by bead to bead processes. 85% of attachment yield was obtained on Cytodex III in this medium, compared to about 93% in 1% serum containing medium. About 90% of the attached HEK cells spreaded after 6 hours of post-attachment periods on the surface of microcarrier. Maximum cell density and scu-PA concentration in a serum free medium were $9.1{\times}10^5$ cells/ml and 1790 IU/ml, respectively, with fed-batch cultivation. Maximum cell density and scu-PA concentration in this medium with perfusion cultivation were $2.5{\times}10^6$ cells/ml and 1820 IU/ml, respectively. The conversion of single chain urokinase type plasminogen activator (scu-PA) into two chain type plasminogen activator (tc-PA) was less than 5% in a serum free medium compared to about 10% in 0.5% serum containing medium.

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Therapeutic Efficacy of Adefovir Dipivoxil in Korean Children and Adolescents with Chronic Hepatitis B who have Developed Lamivudine Resistance (Lamivudine 내성 소아 청소년 만성 B형 간염에서 Adefovir의 치료 효과)

  • Hwang, Su-Kyeong;Park, Sun-Min;Choe, Byung-Ho;Kim, Jung-Mi;Kim, Jung-Ok;Kim, Young-Mi;Lee, Ji-Hye;Cho, Min-Hyun;Tak, Won-Young;Kweon, Young-Oh
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.143-149
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    • 2008
  • Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

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Efficacy of Lamivudine Therapy for Chronic Hepatitis B in Children (소아 만성 B형 간염 환아에서 라미부딘의 치료 효과)

  • Lee, Eun-Hye;Jang, Joo-Young;Kim, Kyung-Mo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.130-136
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    • 2008
  • Purpose: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. Methods: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. Results: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13~58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p>0.05). Conclusion: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.

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A Study on $Digoxin^{(R)}-like$ Immunoreactivity and Its Nature in Patients with Chronic Renal Failure and Neonates (만성 신부전환자 및 신생아 혈청에서 $Digoxin^{(R)}$과 교차 면역반응을 보이는 물질에 관한 연구)

  • Lee, Myung-Shik;Lee, Choong-Ki
    • The Korean Journal of Nuclear Medicine
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    • v.21 no.1
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    • pp.55-60
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    • 1987
  • $Digoxin^{(R)}$을 복용하고 있지 않는 각27명의 만성 신부전 환자 및 신생아의 혈청에서 Gammacoat $Digoxin^{(R)}$ kit와 Amerlex Digoxin $RIA^{(R)}$ kit를 이용하여 digoxin과 교차 면역반응을 보이는 내인성 물질(이하 DLI: Digoxin-like Immunoreactivity)을 측정하여 다음의 결과를 얻었다. 1) Gammacoat $Digoxin^{(R)}$ kit로 측정시 27명의 만성 신부전 환자중 12명에서 신생아의 경우는 27명 전원에서 측정 하한치 이상의 DLI가 검출된 반면, Amerlex Digoxin $RIA^{(R)}$ kit로는 1명을 제외한 양 군의 전원에서 DLI가 관찰되지 않았다. 만성 신부전 환자에서 Gammacoat $Digoxin^{(R)}$ kit로 측정된 DLI와 혈청 BUN/Creatinine 값 사이에는 유의한 상관 관계가 없었다. 2) 만성 신부전 환자 및 신생아의 pooled sera에 가한 digoxin의 수거율은 각각 49%, 40%였다. 3) 만선 신부전 환자 및 신생아의 pooled sera에서 측정되는 DLI의 희석 curve는 정상 희석 curve와 다르다고 할 수 없었다. 4) 만성 신부전 환자의 pooled sera에서 측정되는 DLI의 16%, 그리고 신생아의 pooled sera 에서 측정되는 DLI의 20%가 trypsin에 sensitive하였다. 5) 만성 신부전 환자의 pooled sera에서 측정되는 DLI의 56%가, 그리고 신생아의 pooled sera에서 측정되는 DLI의 경우는 전체의 20%미만이 methylene chloride로 추출되었다. 이상에서 만성 신부전 환자 및 신생아의 혈청에서는 방사면역 kit의 증류에 따라 DLI가 검출되며 그 실체를 알기 위해서는 더욱 연구가 필요하다고 할 수 있었다.

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Effects of Radiation Mutant Perilla frutescens var. crispa in Preventing and Alleviating Symptoms in a Monosodium Iodoacetate-Induced Osteoarthritis Rat Model (MIA로 퇴행성관절염을 유도한 랫드에 방사선 형질전환 차조기가 증상 예방 및 완화에 미치는 효과)

  • Sim, Boo-Yong;Joo, In-Hwan;Kim, Sung-Kyu;Ji, Joong-Gu
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.4
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    • pp.830-838
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    • 2020
  • The present study aimed to evaluate the effect of radiation mutant Perilla frutescens var. crispa on bone metabolism and the inflammatory response in a monosodium iodoacetateinduced rat model of osteoarthritis. radiation mutant Perilla frutescens var. crispa was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 μl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral radiation mutant Perilla frutescens var. crispa for another 4 weeks. It was evaluated that the treatment effects based on serum biomarkers, and morphological and histopathological analysis of the knee joints. Compared with those in control rats, the radiation mutant Perilla frutescens var. crispa treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., COX-2, LTB4, MMP-3, and COMP), and the amount of fibrous tissue. Otherwise, it was significantly increased the concentration of TIMP-1 and calcitonin. In addition, the radiation mutant Perilla frutescens var. crispa treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that radiation mutant Perilla frutescens var. crispa prevented and alleviated osteoarthritis symptoms. Thus, radiation mutant Perilla frutescens var. crispa can be used in food and drug material for the management of osteoarthritis.