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Clinical Pharmacology of Mycophenolic Acid as Immunosuppressant in Organ Transplaantation

  • Kang, Ju-Seop;Lee, Joo-Won;Jhee, Ok-Hwa;Om, Ae-Son;Lee, Min-Ho;Shaw, Leslie M.
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.65-77
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    • 2005
  • Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

Methylation Status of H19 Gene in Embryos Produced by Nuclear Transfer of Spermatogonial Stem Cells in Pig

  • Lee, Hyun-Seung;Lee, Sung-Ho;Gupta, Mukesh Kumar;Uhm, Sang-Jun;Lee, Hoon-Taek
    • Reproductive and Developmental Biology
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    • v.35 no.1
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    • pp.67-75
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    • 2011
  • The faulty regulation of imprinting gene lead to the abnormal development of reconstructed embryo after nuclear transfer. However, the correlation between the imprinting status of donor cell and preimplantation stage of embryo development is not yet clear. In this study, to determine this correlation, we used the porcine spermatogonial stem cell (pSSC) and fetal fibroblast (pFF) as donor cells. As the results, the isolated cells with laminin matrix selection strongly expressed the GFR ${\alpha}$-1 and PLZF genes of SSCs specific markers. The pSSCs were maintained to 12 passages and positive for the pluripotent marker including OCT4, SSEA1 and NANOG. The methylation analysis of H19 DMR of pSSCs revealed that the zinc finger protein binding sites CTCF3 of H19 DMRs displayed an androgenic imprinting pattern (92.7%). Also, to investigate the reprogramming potential of pSSCs as donor cell, we compared the development rate and methylation status of H19 gene between the reconstructed embryos from pFF and pSSC. This result showed no significant differences of the development rate between the pFFs ($11.2{\pm}0.8%$) and SSCs ($13.3{\pm}1.1%$). However, interestingly, while the CTCF3 methylation status of pFF-NT blastocyst was decreased (36.3%), and the CTCF3 methylation status of pSSC-NT blastocyst was maintained. Therefore, this result suggested that the genomic imprinting status of pSSCs is more effective than that of normal somatic cells for the normal development because the maintenance of imprinting pattern is very important in early embryo stage.

Effects of Milk Protein levels and Casein/Whey Ratios on Organ Growth and Protein Metabolism in Early Weaned Rats (조기 이유한 흰쥐에서 유단백질의 섭취수준과 조성비가 기관성장과 단백질대사에 미치는 영향)

  • 박미나
    • Journal of Nutrition and Health
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    • v.30 no.1
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    • pp.3-11
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    • 1997
  • This study was conducted to investigate the effects of protein levels and casein/whey ratios on organ growth and protein metabolism in early weaned rats. Premature rats weaned by the 17th day were fed six semipurified synthetic, isocaloric and gel diets that contained three levels (low, medium and high) and two different combinations(casein/whey ; 80 : 20 or 20 : 80) of milk protein for 8 days. On the 25th day postpartum, frest weigth and DNA, RNA and milk protein contents in brain, liver, kidney and muscle were determined to ascertain organ and cellular growth. Futher, with a view to ascertain protein metabolism and renal functions, serum total protein, $\alpha$-amino N, urea N, and creatinine and creatinine and urinary urea N, creatinine and hydroxproline were determined. Total DNA contents of brain, liver and kidney, which may represent as an index of cell numbers in those organs were significantly decreased in the rats fed diets containing low level protein regardless of casein/whey ratio. However, as fat as the rats fed high protein diets were concerned, their fresh weight, protein contents and GFR of kidney were significantly increased. Furthermore, nitrogen components, $\alpha$-amino N, urea N and creatinie in serum and urine were also increassed. Another observation was that high casein/whey ratio significantly facilitated accumulation of porteins in muscle and kidney and urinary hydorxyproline excretion, not affecting the DNA content of those organs. This study showed that low(8%) or high(32%) contents of protein had less desirable effects either on protein metabolism or on organ cellular growth in prematurely weaned rats, whereas there were no effects on general growth and bone strength.

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The Effect of Pulsatile Flow on Ultrafiltration In-Vitro Study and Comparison with Roller Pump

  • Lee K.;Jeong J. H.;Mun C. H.;Lee J. C.;Min B. G.
    • Journal of Biomedical Engineering Research
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    • v.26 no.5
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    • pp.337-341
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    • 2005
  • Blood pulsation has been reported to have an advantageous effect on extracorporeal blood circulation. However, the study of pulsatile blood flow in renal replacement therapy is very limited. The in-vitro experimental results of pulsatile blood flow on ultrafiltration, when compared with the conventional roller pump, are described in this paper. Methods: Blood flow rate (QB) and transmembrane pressure (TMP) were considered as regulating factors that have an influence on ultrafiltration. Experiments were performed under the condition of equal TMP and OB in both pulsatile and roller pump groups, Several kinds of hollow fiber dialyzers were tested using distilled water containing chemicals as a blood substitute. Mean TMP (mTMP) varied from 10 to 90mmHg while the QB was 200ml/min. Results: Ultrafiltration rate (QUF) was found to be linearly proportional to TMP, whereas QB had little influence on QUF. In addition, QUF was higher in the pulsatile group than the roller pump group at the identical TMP. Conclusion: In the controlled test, QUF increased solely as a consequence of blood pulsation, which implies that the pulse frequency represents an additional and important clinical variable during renal replacement therapy.

The Bisphenol A: A Modulator of Pregnancy in Rats

  • Kim, Pan-Gyi;Lee, Na-Rae;Hwang, Seong-Hee
    • Journal of Environmental Health Sciences
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    • v.29 no.4
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    • pp.27-34
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    • 2003
  • Bisphenol A is used in the manufacture of epoxy, polycarbonate, and corrosion-resistant unsaturated polyester-styrene resins required for food packaging materials in industrial processing. Some reports indicated the possibility of harmful effects on rats. In this study was used a method for the determination of bisphenol A in blood according to the OSHA High Performance Liquid Chromatography (HPLC) guideline. The method involved blood extraction using methylene chloride. And it was evaluated developmental and teratogenic effects in pregnant rats and second generation. The results obtained were as follows. There was a significant increase in the body weights and treated groups F1 female in liver, spleen, kidney, but according to dose-response. F1 female rat's relative body weight and absolute body weight are not different. There was a significant increase liver, spleen, kidney organ weight and reproductive organ weight epididymis, prostate gland in F1 male rats. There was a proestrous in pregnant rat, group 200 $\mu\textrm{g}$/kg, 2000 $\mu\textrm{g}$/kg, 20,000 $\mu\textrm{g}$/kg. The effect on rat treated with bisphenol A decrease organ weight and reproductive organ weight. Identification and quantitation were performed with using HPLC C18 column and using at retention time 5.5 min. The results of the detection of bisphenol A were at 20,000 $\mu\textrm{g}$/kg in average 1 $\mu\textrm{g}$/ml, 200 $\mu\textrm{g}$/kg average in 0.9 $\mu\textrm{g}$/ml blood samples. From those results, it could be concluded that the effects of pregnant rat and second generation(F1) by bisphenol A treatment during lactational period were estrogenic and bisphenol A was remained in serum at low level.

A Convergence Study on the relationships among Attitude toward Death, Spiritual Well-being and Awareness about Organ Donation of Nursing Students (간호대학생의 죽음태도, 영적건강 및 장기기증 인식 간의 관련성에 대한 융합적 연구)

  • Choi, Dongwon;Lim, Junghye
    • Journal of the Korea Convergence Society
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    • v.8 no.5
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    • pp.265-273
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    • 2017
  • This study is convergence study to identify the relationships among attitude toward death(ATD), spiritual well-being(SW) and awareness about organ donation(AAOD). The survey was performed on 214 nursing students in one university. Data was collected using a structured questionnaires and analysed with PASW 20.0. Study findings revealed that AAOD has a significant correlation with ATD and SW. ATD(${\beta}=-.159$), SW(${\beta}=.132$), idea about brain death's organ donation(${\beta}=.314$), and major satisfaction(${\beta}=.134$) about AAOD were most significant predictive variables. These variables accounted for 20.5% of the variance in AAOD. The findings indicate the necessity of developing educational programs to enhance nursing students's ATD and SW for increasing positive AAOD and further rate of organ donation, and follow-up study.

A scanning electron microscope study on the tegument of Proalayioides kobauushii Park, 1940 (Trematoda) (Proalarioides kobayashii Park, 1940의 표피 미세구조)

  • Ju, Jong-Pil;Im, Il-Seong;Hwang, In-Dam
    • Parasites, Hosts and Diseases
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    • v.29 no.2
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    • pp.173-180
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    • 1991
  • A SEM study was performed on the surface of adult P. habayashii Park, 1940, recovered from the snake, Elaphe rufodorsata. The anterior part of the worms was cup-shape and equipped with oral, ventral suckers, pseudosuckers, and tribocytic organ, and the posterior one was finger-like and round-ended, The tegument of the anterior body was covered with 3~4 pointed small spines on the midventral surface and 1~2 pointed ones on the lateral surface. Sensory papillae such as type II, dome-shape ones, and papillae with an opening were distributed over the ventral surface of the anterior portion. The round tribocytic organ was bearing small stout spines laterally, whereas the surface Which comes in contact with the host tissues consisted of numerous long fibrillar fibers. The lip of the oral sucker contained type II papillae. Lateral margin of the anterior body revealed type III papillae.

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Effect of Dietary Phospholipid on the Lipid Components of Serum and Organ Tissues in Rats (식이성 인지질이 흰쥐의 혈청 및 장기조직의 지질성분에 미치는 영향)

  • Jeong, Gyu-Cheol;Lee, In-Sil;Kim, Song-Jeon
    • The Korean Journal of Food And Nutrition
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    • v.2 no.2
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    • pp.40-64
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    • 1989
  • For the study of the effect of dietary phospholipid (PL) on the lipid components of serum and organ tissues in Sprague-Dawley rats, 56 Male-rats were divided into 8 groups, which was composed of 7. One group was fed with basal diet (normal group). And other experimental groups were fed ad libitum with the mixture of carbohydrate. casein salt mixture : vitamin mixture(60:18:4:1) and at the same time fed administratively with 1 gram of phospholipid-free soybean oil, corn oil and sesame oil, and phospholipid-containing soybean oil, corn oil and sesame oil respectively After 60 days the rats were fasted for 12 hours and then decapitated to collect blood and separate organ tissues . The lipid and protein components of serum and organ tissues were analyzed. The results of this study are summarized as follows The supplementation of dietary phospholipid decreases the food efficiency ratio and the growth rate of experimental rats, it increases the level of serum phospholipid and cholesterol ester, but decreases the value of total-cholesterol (T-chol.)/PL ; it decreases the value of albumin/globulin (hyG ratio) of serum protein and it increases the level of phosphatidyl ethanolamine(PE) in serum and organ tissues. And the correlation coefficients among the contents of T-chol., of HDL-chol. and of phospholipid in serum and liver are negative in general. Therefore 1 think that we must eat dietary phospholipid unpurified from vegetable oil to prevent development of atherosclerosis and fat liver.

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Relationship between Developmental Ability and Cell Number of Day 2 Porcine Embryos Produced by Parthenogenesis or Somatic Cell Nuclear Transfer

  • Uhm, Sang Jun;Gupta, Mukesh Kumar;Chung, Hak-Jae;Kim, Jin Hoi;Park, Chankyu;Lee, Hoon Taek
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.4
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    • pp.483-491
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    • 2009
  • In vitro produced porcine embryos have potential application in reproductive biotechnology. However, their development potential has been very low. This study evaluated the in vitro developmental ability and quality of cloned and parthenogenetic porcine embryos having 2-4 cells or 5-8 cells on Day 2 of in vitro culture. Analysis of results showed that 2 to 4 cell embryos had higher ability to form blastocysts than 5 to 8 cell embryos (p<0.05). Blastocysts produced from culture of 2 to 4 cell embryos also contained higher cell numbers and had lower BAX:BCLxL transcript ratio than those produced from 5 to 8 cell embryos (p<0.05), thereby suggesting 2 to 4 cell embryos have higher development potential. Further investigation revealed that 5 to 8 cell embryos had higher incidence (100${\pm}$0.0%) of blastomeric fragmentation than 2 to 4 cell embryos (15.2${\pm}$5.5% for parthenogenetic and 27.7${\pm}$7.1% for cloned embryos). This suggests that low development potential of 5 to 8 cell embryos was associated with blastomeric fragmentation. In conclusion, we have shown that morphological selection of embryos based on cell number on Day 2 of in vitro culture could offer a practical and valuable non-invasive means to select good quality porcine embryos.

Organ-sparing Surgery in Treating Patients with Liposarcoma of the Spermatic Cord: Institutional Experience and Pooled Analysis

  • Cao, Ming-Xin;Chen, Jie;Zhang, Jun-Long;Wei, Xin;Liang, Yue-You
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3419-3423
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    • 2015
  • Background: Liposarcoma of the spermatic cord is rare and frequently misdiagnosed. The standard therapeutic approach has been radical inguinal orchiectomy with wide local resection of surrounding soft tissues. The current trend of organ preservation in the treatment of several cancers has started to evolve. Herein we present our testis-sparing surgery experience in the treatment of spermatic cord liposarcoma and a pooled analysis on this topic. Materials and Methods: Clinical information from patient receiving organ-sparing surgery was described. Clinical studies evaluating this issue were identified by using a predefined search strategy, e.g., Pubmed database with no restriction on date of published papers. The literature search used the following terms: epidemiology, surgery, chemotherapy, radiotherapy, testis sparing surgery, spermatic cord sarcomas/liposarcomas. Results: Patient received a complete excision of the lesion, preserving the spermatic cord and the testis. The final pathological report showed a well differentiated liposarcoma with negative surgical margins and no signs of local invasion. After 2-year of follow-up, there was no evidence of local recurrence. Since the first case reported in 1952, a total of about 200 well-documented spermatic cord liposarcoma cases have been published in English literature. Among these patients, only three instances were reported to have received an organ-sparing surgery in the treatment of spermatic cord liposarcoma. Conclusions: Radical inguinal orchiectomy and resection of the tumor with a negative microscopic margin is the recommended treatment for liposarcoma of the spermatic cord. But for small, especially well-differentiated, lesions, testis-sparing surgery might be a good option if an adequate negative surgical margin is assured.