• Title/Summary/Keyword: erythropoietin (EPO)

Search Result 140, Processing Time 0.025 seconds

A Study for Improvement of Erythropoietin Responsiveness in Hemodialysis Patients (혈액 투석 환자에서 조혈 호르몬 치료 효과 향상에 대한 연구)

  • Park, Jong-Won;Do, Jun-Yeung;Yoon, Kyung-Woo
    • Journal of Yeungnam Medical Science
    • /
    • v.18 no.2
    • /
    • pp.226-238
    • /
    • 2001
  • Background: Anemia in chronic renal failure plays an important role in increasing morbidity of dialysis patients. The causes of the anemia are multifactorial. With using of erythropoietin(EPO) most of uremia-induced anemia can be overcome. However, about 10% of renal failure patients shows EPO-resistant anemia. Hyporesponsiveness to EPO has been related to many factors: iron deficiency, aluminum intoxication, inflammations, malignancies and secondary hyperparathyroidism. So I evaluated the improvement of EPO responsiveness after correction of above several factors. Materials and Methods: Seventy-two patients on hemodialysis over 6 months were treated with intravenous ascorbic acid(IVAA, 300 mg t.i.w. for 12 weeks), After administration of IVAA for 12 weeks, patients were classified into several groups according to iron status, serum aluminum levels and i-PTH levels. Indivisualized treatments were performed: increased iron supplement for absolute iron deficiency, active vitamin D3 for secondary hyperparathyroidism and desferrioxamine(DFO, 5 mg/kg t.i.w.) for aluminum intoxication or hyperferritinemia. Results: 1) Result of IVAA therapy for 12 weeks on all patients(n=72). Hemoglobin levels at 2, 4, 6 week were significantly elevated compared to baseline, but those of hemoglobin at 8, 10, 12 week were not significantly different. 2) Result of IVAA therapy for 20 weeks on patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and transferrin saturation(Tsat) below 30%(n=30). After treatment of IV AA for 12 weeks, patients were evaluated the response of therapy according to iron status. Patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and Tsat below 30% showed the most effective response. These patients were treated further for 8 weeks. Hemoglobin levels at 2, 4 week were significantly increased compared to baseline with significantly reduced doses of EPO at 2, 4, 6, 10, 12, 16, 20 week. Concomitantly significantly improvement of Tsat at 2, 6, 16, 20 week compared to baseline were identified. 3) Result of IVAA therapy for 12 weeks followed by DFO therapy for 8 weeks on patients with serum aluminum above 4 ${\mu}g/l$(n=12) Hemoglobin levels were not significantly increased during IVAA therapy for 12 weeks but dosages of EPO were significantly decreased at 2, 4, 6, 8 week during DFO therapy compared to pre-treatment status. Conclusion: IVAA can be helpful for the treatment of the anemia caused by functional iron deficiency and can reduce the dosage of EPO for anemia correction. And administration of low dose DFO, in cases of increased serum aluminum level, can reduce the requirement of EPO.

  • PDF

Revisiting Use of Growth Factors in Myelodysplastic Syndromes

  • Newman, Kam;Maness-Harris, Lori;El-Hemaidi, Ihab;Akhtari, Mojtaba
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.4
    • /
    • pp.1081-1091
    • /
    • 2012
  • Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematologic neoplasms characterized by morphologic dysplasia, aberrant hematopoiesis and peripheral blood refractory cytopenias. MDS is recognized to be associated with an increased risk of symptomatic anemia, infectious complications and bleeding diathesis, as well as a risk of progression to acute myeloid leukemia, particularly in patients with a high IPSS score. The advent of use of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and recombinant erythropoietin (EPO) has improved symptoms in MDS patients in addition to some data that suggest there might be an improvement in survival. G-CSF is an effective therapeutic option in MDS patients, and it should be considered for the management of refractory symptomatic cytopenias. G-CSF and EPO in combination can improve outcomes in appropriate MDS patients such as those with lower-risk MDS and refractory anemia with ring sideroblasts (RARS). This article reviews use of growth factors for lower-risk MDS patients, and examines the data for G-CSF, EPO and thrombopietic growth factors (TPO) that are available or being developed as therapeutic modalities for this challenging disease.

Anti-calcification of Bovine Pericardium for Bioprosthetic Heart Valves after Surface Modification with Hyaluronic Acid Derivatives

  • Hahn Sei Kwang;Ohri Rachit;Giachelli Cecilia M.
    • Biotechnology and Bioprocess Engineering:BBE
    • /
    • v.10 no.3
    • /
    • pp.218-224
    • /
    • 2005
  • Surface modification of glutaraldehyde fixed bovine pericardium (GFBP) was success­fully carried out with hyaluronic acid (HA) derivatives. At first, HA was chemically modified with adipic dihydrazide (ADH) to introduce hydrazide functional group into the carboxyl group of HA backbone. Then, GFBP was surface modified by grafting HA-ADH to the free aldehyde groups on the tissue and the subsequent HA-ADH hydrogel coating. HA-ADH hydrogels could be prepared through selective crosslinking at low pH between hydrazide groups of HA-ADH and crosslinkers containing succinimmidyl moieties with minimized protein denaturation. When HA­ADH hydrogels were prepared at low pH of 4.8 in the presence of erythropoietin (EPO) as a model protein, EPO release was continued up to $85\%$ of total amount of loaded EPO for 4 days. To the contrary, only $30\%$ of EPO was released from HA-ADH hydrogels prepared at pH=7.4, which might be due to the denaturation of EPO during the crosslinking reaction. Because the carboxyl groups on the glucuronic acid residues are recognition sites for HA degradation by hyaluronidase, the HA-ADH hydrogels degraded more slowly than HA hydrogels prepared by the crosslinking reaction of divinyl sulfone with hydroxyl groups of HA. Following a two-week subcutaneous implantation in osteopontin-null mice, clinically significant levels of calcification were observed for the positive controls without any surface modification. However, the calcification of surface modified GFBP with HA-ADH and HA-ADH hydrogels was drastically reduced by more than $85\%$ of the positive controls. The anti-calcification effect of HA surface modification was also confirmed by microscopic analysis of explanted tissue after staining with Alizarin Red S for calcium, which followed the trend as observed with calcium quantification.

WAP-EPO 유전자 도입 형질전환돼지의 계대번식시 유전자 전이효율에 관한 연구

  • 이연근;박진기;민관식;성환후;임기순;양병철;김광식;김진회;장원경
    • Proceedings of the KSAR Conference
    • /
    • 2001.03a
    • /
    • pp.14-14
    • /
    • 2001
  • 본 연구는 생명공학 관련 기술개발에 의하여 신소재 물질을 생산하고 사람에게 안전하고 생리활성이 높은 고가의 의료용 단백질 생산기술을 체계화하며 형질전환 가축을 이용한 유용물질 생산에 따른 산업화와 부가가치의 극대화에 그 목적이 있다. 유즙으로 사람의 빈혈치료제인 EPO(Erythropoietin)를 분비할 수 있는 형질전환돼지를 생산하기 위하여 WAP(Whey Acidic Protein) Promoter(2.6kb) 하류에 사람의 조혈촉진유전자(EPO: 2.6kb)를 연결시켜 미세주입용 재조합 벡터(WAP-EPO : 약 7.8kb)를 구축하였다. 구축된 재조합 벡터를 1세포기 수정란에 약 2ng/ul 농도로 미세주입한 다음 외과적 방법으로 이식하였다. 이식 후 분만 모돈으로부터 생산된 자돈의 꼬리조직을 이용 게놈DNA를 추출하고 PCR 검정을 한 결과, 유즙으로 사람의 빈혈치료제를 생산할 수 있는 유전자가 도입된 형질전환돼지 $\boxDr$새롬이$\boxUl$ (♂)를 확인하였다. 또한 이렇게 꼬리조직으로부터 확인된 새롬이의 혈액과 정액을 채취, 게놈 DNA를 추출하여 외래 유전자 삽입여부를 PCR 방법으로 검정한 결과 꼬리조직과 마찬가지로 혈액 및 정액에서도 외래유전자가 삽입되었음을 확인할 수 있었다. 이렇게 생산된 형질전환돼지 $\boxDr$새롬이$\boxUl$를 이용 계대번식을 통한 F$_1$ 산자의 생산과 유전자 전이율을 확인하기 위하여 $\boxDr$새롬이$\boxUl$정액을 이용한 인공수정을 실시하였다. 인공수정은 1999년 7월 1일부터 2000년 9월 8일 까지 총 78두의 모돈을 이용하였으며, 그 중 21두의 모돈이 분만하여 인공수정에 의한 분만율은 26.92%로 나타났다.(Table Omitted) Table 1에서와 같이 새롬이 정액을 이용한 인공수정에 의해 형질전환된 F$_1$ 자돈의 형질전환율은 17.98%로 나타났으며, 32두의 형질전환자돈 중 8두(암:4두, 수:4두)는 분만과 동시에 폐사하였거나 사육중 폐사하여 현재 24두(암:12두, 수:12두)가 생존하여 F$_1$ 간 교배계획에 의해 사육되고 있다. 이 중 암컷 4두는 현재 F$_2$ 자돈 생산과 함께 유즙내로 사람 빈혈치료제의 분비 유무를 검정중에 있으며, FISH 법에 의한 외래 유전자 삽입 검정을 확인 중에 있다.

  • PDF

형질전환돼지의 과배란 유기시 성호르몬의 변화

  • 이현기;이풍연;박진기;이연근;장원경
    • Proceedings of the KSAR Conference
    • /
    • 2004.06a
    • /
    • pp.219-219
    • /
    • 2004
  • Human erythropoietin (hEPO) 유전자가 도입된 형질전환돼지는 수태와 임신율을 일반돼지와 비교를 해 보았을 때 매우 낮은 경향을 보이는 것으로 나타났으며, 이러한 경향의 원인을 구명하기 위하여 인위적인 발정동기화 및 호르몬을 이용한 과배란 유기시 배란과 수정(수태)시 성호르몬 변화를 비교하고자 실시하였다. 먼저 발정동기화를 위하여 PG 600 (PMSG 400 IU, HCG 200IU)을 주사한 후 10일 후에 Regumate porcine을 6일간 급여한 후에 PMSG 주사하고 2일 후에 hCG 주사한 다음 인공수정을 실시하였다. (중략)

  • PDF

Production of Transgenic Bovine Embryos Following Nuclear Transfer of Bovine Fetal Fibroblasts Transfected by Foreign Genes (외래유전자를 도입한 소 태아세포의 핵치환에 의한 형질전환 소 수정란 생산)

  • Kil, K.S.;Uhm, S.J.;Kim, E.H.;Chung, H.J.;Kim, T.;Park, H.;Lee, H.T.;Chung, K.S.
    • Korean Journal of Animal Reproduction
    • /
    • v.24 no.4
    • /
    • pp.429-437
    • /
    • 2000
  • This study investigated the successful introduction of genes of erythropoietin (EPO) and enhanced green fluorescent protein (EGFP) in bovine embryos following nuclear transfer of bovine fetal fibroblasts (bFF), which were transfected by retrovirus vector system. Non-starved bFF were, transferred into perivitelline space of enucleated oocytes. The bFF-oocyte units were accomplished by cell to cell fusion and activated with calcium inophore and 6-dimethylaminopurine. Reconstructed embryos were co-cultured with bovine oviduct epithelial cells in CRlaa medium for 8 days. Out of 187 (EPO) and 210 (EGFP) bovine eggs reconstructed by nuclear transfer, 149 (EPO : 80.0%) and 158 (EGFP : 75.2%) embryos were cleaved, and among them 36 (EPO : 24.2%) and 35 (EGFP : 22.2%) embryos developed to the blastocyst stage. Of these blastocysts, 100% integration of EPO gene in 36 embryos was determined by PCR, and 100% expression of EGFP gene in 35 embryos was observed under the fluorescent microscope. This result indicates that bovine oocytes reconstructed by nuclear transfer of transfected bFF can successfully develop to the blastocyst stage. Furthermore, this novel procedure may be presumably an attractive method efficiently to produce the transgenic cattles.

  • PDF

Studies on Local Irritation of DA-3585, A Recombinant Human Erythropoietin, in Rabbits (DA-3585(recombinant human erythropoietin)의 국소자극성에 관한 연구)

  • Cho, Hyeon;Kim, Dong-Hwan;Kang, Kyung-Koo;Park, Jang-Hyeon;Lee, Sung-Hee;Kim, Won-Bae
    • Toxicological Research
    • /
    • v.14 no.3
    • /
    • pp.393-400
    • /
    • 1998
  • As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.

  • PDF

Pharmacokinetics and Tissue Distribution of Recombinant Human Erythropoietin (DA-3285) in the Laboratory Animals (Recombinant human erythropoietin (DA-3285)의 실험동물에서의 약동력학 및 조직분포)

  • 심현주;이응두;이종진;김흥재;이상득;이성희;김원배;양중익
    • Biomolecules & Therapeutics
    • /
    • v.4 no.1
    • /
    • pp.78-83
    • /
    • 1996
  • The pharmacokinetics and tissue distribution of DA-3285 (recombinant human erythropoietin, recently manufactured by Research Laboratories of Dong-A Pharmaceutical Company) were studied in the laboratory animals. The plasma, urine, and tissue concentration of DA-3285 were measured by a double-antibody sandwich enzyme immunoassay. After intravenous administration of DA-3285, 20, 100, 500 and 2500 units/kg to rats, the plasma concentrations declined polyexponentially with the terminal half-lives of 2.15, 2.10, 2.31, and 2.35 hr, respectively. Total body clearance (20.7∼26.6 mι/hr/kg) and apparent volume of distribution at steady state (57.2∼70.1 mι/kg) were independent of the dose and AUC increased proportionally with the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism , plays a significant role in elimination of DA-3285. In all rat tissues, the tissue to plasma ratios were smaller than unity, indicating less affinity of DA-3285 to rat tissues and was proved by considerably less value of Vdss. After 3 times a week for consecutive 3 weeks i.v. administration of DA-3285, 100 units/kg to rats, the plasma concentrations and pharmacokinetic parameters of DA-3285 were not significantly different from those in a single administration. After s.c. administration to the rat, plasma concentrations of DA-3285 peaked at 6 hr and the extent of bioavailability was 26.7%. In mice, rabbits and dogs, at DA-3285 dose of 100 units/kg, the mean terminal haw-lives were 2.78, 3.05, and 4.01 hr, respectively. Compared with reported data in the literatures, DA-3285 has similar properties to rh-EPO manufactured by other companies in view of pharmacokinetics.

  • PDF

Study on the Reproductive Function in Transgenic Pig Harboring Human Erythropoietin (hEPO) Gene

  • Lee, Hyun-Gi;Lee, Hwi-Cheul;Chung, Hak-Jae;Hwang, In-Sul;Choi, Myoung-Seob;Byun, Sung-June;Lee, Seung-Hoon;Kim, Min-Ji;Woo, Jae-Seok;Chang, Won-Kyong;Lee, Poong-Yeon;Lee, Hoon-Taek;Park, Jin-Ki
    • Reproductive and Developmental Biology
    • /
    • v.32 no.2
    • /
    • pp.117-121
    • /
    • 2008
  • Our previous study showed that transgenic (TG) pigs harboring human EPO (hEPO) gene have been shown to have reproductive disorders, including low pregnancy rates, irregular estrus cycle and low little size. To investigate these reasons, we assessed estrus behavior (standing response) and plasma $17{\beta}$-estradiol ($E_2$) level, which partly reflect reproductive function, during the estrus cycles after synchronization and superovulation by hormone treatments. Then, we analysed blood composition and expression of hEPO gene in TG pigs. Pigs were injected with PG600. After 10 days, pigs were fed with Regumate porcine for 6 days. Blood samples were collected from jugular vein. Analysis of blood composition and $E_2$ level were measured by Hemavet 950 and $E_2$ ELISA kit, respectively. And, the expression of hEPO gene in reproductive organs was quantitated by real-time RT-PCR. The percentage of estrus behavior in TG was significantly decreased. Hematocrit (HCT), hemoglobin (Hb) concentration and red blood cell (RBC) number were significantly higher in TG than wild type (WT). On the other hand, high expression of hEPO gene in TG was observed in the mammary gland as well as in the uterus. Moreover, plasma $E_2$ level was significantly higher in TG than WT. These results suggest that nonspecific expression of hEPO gene in the other organs of TG may affect blood composition and plasma $E_2$ level, thereby causing reproductive disorders.

Sperm Fertility of Transgenic Boar Harboring hEPO Gene is Decreased

  • Park Chun-Gyu;Kim Sung-Woo;Lee Poong-Yeon;Han Joo-Hee;Lee Hyun-Gi;Byun Sung-June;Yang Boh-Suk;Lee Chang-Hyung;Lee Hoon-Taek;Chang Won-Kyong;Park Jin-Ki
    • Reproductive and Developmental Biology
    • /
    • v.30 no.1
    • /
    • pp.27-34
    • /
    • 2006
  • This study was conducted to compare the reproduction ability of the wild type boar and recombinant human erythropoietin (hEPO) transgenic boar semen. Ejaculated boar semen was analyzed by flow cytometry, Elisa and IVF methods. In experiment 1, flow cytometric analysis showed that the live sperm ratio of transgenic boar sperm significantly lower (P<0.05) than that of wild type boar after incubation at 20, 22, 24 and 26 hr. In experiment 2, the presence and levels of various cytokines (IL-6, IL-10 and $TNF-{\alpha}$) to related animal reproduction in the seminal and blood plasma were examined using specific enzyme immunoassay. There was no significant difference between both groups. In experiment 3, the fertilizing capacity and developmental ability of both boar sperm were compared. The transgenic boar sperm had a significantly low capacity of penetration, sperm-zona binding, embryo development, and blastocyst formation compared to wild type sperm (P<0.05). These results suggest that transgenic boar sperm harboring hEPO gene has low sperm viability than wild type boar, and it is a reason to decrease of fertility and litter size.