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Effect of Antibody Titer on Xenograft Survival in Pig-To-Dog Heterotopic Cardiac Xenotransplantation -Opening of Xenotrasplantation Era- (돼지\longrightarrow개 이소이종심장 이식모델에시 생존에 미치는 항체 역가의 영향 -이종이식시대의 개막-)

  • 이정렬;김희경;김지연;최대영;이재형;위현초;강희정;김영태;강병철
    • Journal of Chest Surgery
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    • v.37 no.5
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    • pp.391-400
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    • 2004
  • Xenotransplantation in discordant species results in immediate and irreversible hyperacute rejection due to natural antibodies, IgM. With this, antibody depletion is one option to reduce hyperacute rejection, we investigated the effect of PCPP (postcentrifugal plasmapheresis) on the depletion of natural antibodies and the effect of antibody titer on xenograft survival. Material and Method: Outbred swines (n=4) weighing 10∼20 kg were used as donors and mongrel dogs (n=4) weighing 25∼30 kg were used as recipients. Recipient canines underwent plasmapheresis (COBE TPE Laboratories, Lakewood. CO, USA). Pre-transplantation PCPP was peformed on day -2 and day 0. There were three groups (Group 0: no PCPP, Group 1: 1 pla sma-volume (PV) at day -2 and 2 PV at day 0, Group 2: 2 PV at day -2 and 2 PV at day 0). A swine heart was heterotopically transplanted into a recipient's abdominal infrarenal aorta and inferior vena cava. Mean percent depletion of total IgM and IgG in plasma of the recipients was calculated. Serum albumin, electrolyte, complement activity and coagulation factors were measured. Histopathologic examination of heart specimens was performed. Result: Mean percent depletion of IgM and IgG were 95.7$\pm$1.2%, 80.5$\pm$2.4% in the group 2 at the end of PCPP. The percent depletion of serum albumin concentration was decreased from 2.8 to 1.4 g/㎗ in the group 1 and 3.0 to 1.5 g/㎗ in the group 2. Complement hemolytic activity was decreased in group 1 and 2, but returned to normal level within 24 hours. Complement hemolytic activity was reduced to 10% of pre-PCPP level in group 2. Serum fibrinogen decreased to 20% or less and was recovered within 24 hours in group 2. Antithrombin III decreased but less than fibrinogen. PT and aPTT were sometimes but not always prolonged during plasmapheresis. After plasmapheresis, PT and aPTT were prolonged beyond the measurable level. D-dimer was not found during PCPP, but appeared and maintained from 10 minutes after trasplantation. Graft Survival time was 5 min in group 0, and it was 90$\pm$0 min in the group 2. Histopathologic changes were more typically characterized by edema, hemorrhages, thrombosis in all groups at the end of experiment. Conclusion: PCPP effectively removed immuoglobulins and reduced the titer of natural antibodies, as a result, significantly prololonged swine heart xenograft survival.

Protective Effects of Korean Panax Ginseng Extracts against TCDD-induced Toxicities in Rat (랫드에서 TCDD 투여에 의해 유도된 생체독성의 고려홍삼 추출물에 의한 억제 효과)

  • Choi, Soo-Jin;Sohn, Hyung-Ok;Shin, Han-Jae;Hyun, Hak-Cheol;Lee, Dong-Wook;Song, Yong-Bum;Lee, Soo-Hyun;Gang, Dong-Ho;Lim, Hak-Seob;Lee, Cheol-Won;Moon, Ja-Young
    • Journal of Ginseng Research
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    • v.32 no.4
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    • pp.382-389
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    • 2008
  • To achieve a better understanding of protective effects of water extracts of Panax ginseng against TCDD-induced toxicities, we monitored physiological and clinical changes in rat for 4 weeks after administrations of each Panax Ginseng extract or TCDD, and co-administration of the two materials. For this study, 120 male Sprague-Dawley (SD) rats weighing 190-210 g each (8 weeks old) were divided into four groups: TCDD-administered, co-administered group with TCDD and ginseng extract, ginseng extract-administered, and control group. The TCDD-administered group received single dose of TCDD in a corn oil vehicle ($25\;{\mu}g/kg$ body weight) by intraperitoneal administration on Day 1. The Panax ginseng extracts-administered group received intraperitoneally 100 mg/kg body weight every other day for one month. For the co-administered group with TCDD and ginseng extracts, Panax ginseng extracts were intraperitoneally administered to rats at 100 mg/kg body weight every other day for one month after a single intraperitoneal dose of $25\;{\mu}g$ of TCDD/kg body weight on Day 1. Panax ginseng extracts attenuated the mortality induced by TCDD administration. The extracts also slightly attenuated the TCDD-induced body weight loss. Administration of TCDD alone increased liver weight at 2, 5, and 16 days after administration of TCDD. Administration of Panax ginseng extracts rather decreased liver weight through whole the experimental period, but which was statistically insignificant. Administration of TCDD alone at $25\;{\mu}g/kg$ body weight increased both serum enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at 32 days, indicating that liver damage occurred maximally at that time. Ginseng extract administration caused insignificant changes in serum ALT, but gradually decreased in AST as the exposure time increased. Coadministration of TCDD and ginseng extracts caused serum AST activity to significant recovery to normal value at 16 days and 32 days after exposure to TCDD. The extracts also significantly decreased the TCDD-induced ALT activity after 16 days of TCDD administration. These results suggest that Panax ginseng extracts may possess a protective effect against TCDD-induced toxicities including hepatotoxicity in rats.

The Effect of Recombinant Human Epidermal Growth Factor on Cisplatin and Radiotherapy Induced Oral Mucositis in Mice (마우스에서 Cisplatin과 방사선조사로 유발된 구내염에 대한 재조합 표피성장인자의 효과)

  • Na, Jae-Boem;Kim, Hye-Jung;Chai, Gyu-Young;Lee, Sang-Wook;Lee, Kang-Kyoo;Chang, Ki-Churl;Choi, Byung-Ock;Jang, Hong-Seok;Jeong, Bea-Keon;Kang, Ki-Mun
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.242-248
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    • 2007
  • Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

The Efficacy of the Change in Belly Board Aperture Location by the Addition of Bladder Compression Device for Radiotherapy of Rectal Cancer (직장암 환자의 골반 방사선치료에서 벨리보드 하위 경계 위치 변화의 영향)

  • Yoon, Hong-In;Chung, Yoon-Sun;Kim, Joo-Ho;Park, Hyo-Kuk;Lee, Sang-Kyu;Kim, Young-Suk;Choi, Yun-Seon;Kim, Mi-Sun;Lee, Ha-Yoon;Chang, Jee-Suk;Cha, Hye-Jung;Seong, Jin-Sil;Keum, Ki-Chang;Koom, Woong-Sub
    • Radiation Oncology Journal
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    • v.28 no.4
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    • pp.231-237
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    • 2010
  • Purpose: We investigated the effect of location changes in the inferior border of the belly board (BB) aperture by adding a bladder compression device (BCD). Materials and Methods: We respectively reviewed data from 10 rectal cancer patients with a median age 64 years (range, 45~75) and who underwent computed tomography (CT) simulation with the use of BB to receive pelvic radiotherapy between May and September 2010. A CT simulation was again performed with the addition of BCD since small bowel (SB) within the irradiated volume limited boost irradiation of 5.4 Gy using the cone down technique after 45 Gy. The addition of BCD made the inferior border of BB move from symphysis pubis to the lumbosacral junction (LSJ). Results: Following the addition of BCD, the irradiated volumes of SB and the abdominopelvic cavity (APC) significantly decreased ($174.3{\pm}89.5mL$ vs. $373.3{\pm}145.0mL$, p=0.001, $1282.6{\pm}218.7mL$ vs. $1,571.9{\pm}158mL$, p<0.001, respectively). Bladder volume within the treated volume increased with BCD ($222.9{\pm}117.9mL$ vs. $153.7{\pm}95.5mL$, p<0.001). The ratio of irradiated bladder volume to APC volume with BCD ($33.5{\pm}14.7%$) increased considerably compared to patients without a BCD ($27.5{\pm}13.1%$) (p<0.001), and the ratio of irradiated SB to APC volume decreased significantly with BCD ($13.9{\pm}7.6%$ vs. $24.2{\pm}10.2%$, p<0.001). The ratios of the irradiated SB volume and irradiated bladder volume to APC volume negatively correlated (p=0.001). Conclusion: This study demonstrated that the addition of BCD, which made the inferior border of BB move up to the LSJ, increased the ratio of the bladder to APC volume and as a result, decreased the irradiated volume of SB.