• Title/Summary/Keyword: PGF_{2}$${\alpha}$

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Effect of Different Feeding Ratios of Whole Crop Barley Silage on the Embryo Production in Hanwoo Donors

  • Son, Dong-Soo;Choe, Chang-Yong;Cho, Sang-Rae;Kim, Nam-Tae;Kim, Hyun-Jong;Yeon, Seong-Heum;Ryu, Il-Sun;Son, Jun-Kyu;Choi, Sun-Ho;Kim, Ill-Hwa
    • Journal of Embryo Transfer
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    • v.24 no.4
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    • pp.265-269
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    • 2009
  • The purpose of this study was to determine the effect of different feeding ratios of whole crop barley silage on the embryo production in Hanwoo donors. All donors were basically fed 2.5 kg concentrate daily. Donors were divided into three groups according to the different feeding of forage; hay 70% and rice straw 30% (control, n = 21), whole crop barley silage 80% and rice straw 20% (T1, n = 25), and whole crop barley silage 60% and rice straw 40% (T2, n = 23) fed based on TDN 6.70/ BW 500 kg. All Hanwoo donors received a CIDR together with injections of 1 mg estradiol benzoate and 50 mg progesterone ($P_4$, Day 0). Four days later, they were superovulated with 28 mg FSH twice daily IM in decreasing doses over 4 days. Then donors received 2 doses of $PGF_2{\alpha}$ (25 and 15 mg) with the 5th and 6th injections of FSH on Day 6. CIDR were withdrawn at the 6th FSH injection and the donors received $100\;{\mu}g$ GnRH 36 h after the second $PGF_2{\alpha}$ injection. The donors were artificially inseminated twice, at 8 and 24 h after GnRH, and embryos were recovered 7 or 8 days after the 1st insemination. The flush rate of the donors following positive superovulation responses did not differ among groups (76.2~96.0%, p>0.05). The number of corpus luteum (CL) at embryo recovery also did not differ among groups (10.6~14.0, p>0.05). Furthermore, the mean numbers of total ova (9.4, 10.5 and 12.0) and transferable embryos (5.3, 12.0 and 6.5) did not significantly differ among the control, T1 and T2 groups, respectively (p>0.05). However, mean concentrations of serum $P_4$ of the T1 (64.2 ng/ml) and T2 groups (55.7 ng/ml) were higher than that of control group (43.3 ng/ml, p<0.01), while serum cholesterol concentrations in the control (105.8 mg/dl) and T2 groups ($96.9\;{\pm}\;mg/dl$) were significantly lower than in the T1 group (121.1 mg/dl, p<0.05). Conclusively, whole crop barley silage can be fed a good substitute for hay forage for Hanwoo donors. Furthermore the ratios of whole crop barley silage 60% and rice straw 40% might be more worthful for embryo production.

Superovulation Response and Quality of Embryos Recovered from Cattle after a Single Subcutaneous Injection of FSH Dissolved in Polyethylene Glycol (PEG 융해 FSH 투여방법에 따른 소 과배란 유기 및 수정란이식 효율)

  • 최상용;최수호;박용수;조상래;강태영
    • Journal of Embryo Transfer
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    • v.17 no.1
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    • pp.67-77
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    • 2002
  • This study was carried out to assess the effect of superovulation response and quality of embryos recovered from donor cows after a single subcutaneous injection of FSH dissolved in polyethylene glycol (PEG). Cows were allocated into control and 3 experimental treatment groups. In control, cows were injected intramuscularly 50 mg FSH twice daily for 4 days. Group 1 were injected subcutaneously with a single dose of 400 mg FSH dissolved in 30% PEG solution. Group 2 were injected subcutaneously with a single dose of 200 mg FSH dissolved in 30% PEG solution. Finally in group 3, cows were injected twice 200 mg FSH dissolved in 30% PEG solution by subcutaneous. Superovulation was initiated by injection of FSH between Day 8 and 14 of the estrus cycle (Day 0, the day of estrus), and followed by injection of 25 mg PGF$_2$$\alpha$ at 48 h after first FSH injection. Cows were then artificially inseminated (AI) with semen twice at 48 and 60 h after PGF$_2$$\alpha$ injection. At 7 days after the second AI, embryos collected non-surgically by flushing the uterine horns and were counted and compared morphologically as being transferable and degenerated among different superovulation treatments. Furthermore, progesterone and estradiol -17 $\beta$ in plasma were measured by radioimmunoassay following different treatments at given days All cows of treated groups were observed heat. but control group was showed 77.8%. Superovulation response was observed as 77.8, 87.5, 88.9, and 100% in control, Groups 1, 2 and 3 The mean number of corpus lutea (CL) detected in Group 1 were 19.6, which was, respectively significantly (P<0.05) higher than those of other groups (11.1, 13.4 and 7.6, respectively). However, there did not differ on the mean number of total embryos recovered and of transferable embryos between control and treated groups.

Effects of cyclopiazonic acid and aflatoxin B1 on arachidonic acid metabolism, calcium mobilization and ultrastructure in rabbit platelet aggregation (Cyclopiazonic acid 및 aflatoxin B1이 토끼의 혈소판에서 arachidonic acid 대사, 칼슘 동원 및 초미세구조에 미치는 영향)

  • Hong, Choong-man;Jang, Dong-deuk;Cho, Myung-haing
    • Korean Journal of Veterinary Research
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    • v.36 no.4
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    • pp.873-886
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    • 1996
  • For better understanding the interrelationship of hemorrhage and aggregation mechanism, cyclopiazonic acid(CPA) known as promoting the aggregation of platelet, aflatoxin $B_1(AFB_1)$ inhibiting platelet aggregation were used as toxic mycotoxins in these studies. In order to investigate the potential role of prostaglandin metabolism on the platelet aggregation, a variety of prostaglandin metabolites such as $PGF_{2{\alpha}}$, $PGE_2$ and $TXB_2$ were measured in homogenized rabbit platelets by TLC and LSC. And the role of $Ca^{{+}{+}}$ on the platelet aggregation was investigated by flow cytometer. Finally, the morphological effects of mycotoxins on platelet were determined by transmission electron microscope. The results and conclusions obtained from these studies are: 1) CPA induced no changes but $AFB_1$ increased $PGE_2$ and $TXB_2$. 2) CPA promoted ADP, collagen, thrombin, A.A., and PAF-induced $Ca^{{+}{+}}$ release. $AFB_1$, however, decreased $Ca^{{+}{+}}$ level except collagen-induced $Ca^{{+}{+}}$ release. When the calcium blocker, verapamil, was used, CPA decreased thrombin-induced $Ca^{{+}{+}}$ release and increased collagen, ADP, PAF and A.A.-induced $Ca^{{+}{+}}$ release. $AFB_1$ in contrast decreased the all factors induced $Ca^{{+}{+}}$ release. 3) $AFB_1$ did not induce any ultrastructural changes except large vacuole formation in a few platelets. And CPA also did not induce any changes except moderate shape change, indicator of platelet activation. In conclusion, CPA promoted platelet aggregation by the increases of $Ca^{{+}{+}}$ release but had no changes in A.A. metabolites. Antiaggregating effects of $AFB_1$ may be due to decreases of $Ca^{{+}{+}}$ release and increases of $PGE_2$ and $PGF_{2{\alpha}}$ formation. These data provide the basis for the future study of mobilization and function of $Ca^{{+}{+}}$ in platelet aggregation.

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A Study on Establishment of Quality Management System (ISO 9001 : 2000/ KS A9001 : 2001) based on ERP (ERP 기반의 품질경영시스템(ISO 9001 : 2000/ KS A 9001:2001) 구축에 관한 연구)

  • 김용직;강창욱
    • Proceedings of the Society of Korea Industrial and System Engineering Conference
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    • 2002.05a
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    • pp.413-419
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    • 2002
  • 본 연구의 목적은 품질경영시스템의 ISO 9000:2000/KS A 9000:2001 개정 규격 내용 및 요구사항을 살펴보는 한편, 우리나라 중소기업이 전환규격을 적용하는데 있어서 ERP PACKAGE를 이용하여 효과적인 품질경영시스템 구축 방안을 제시하기 위함이다. 본 연구에서는 업무 PROCESS와 품질 기록을 중심으로 ISO 9000:2000/KS A 9000:2001 개정 규격을 ERP PACKAGE에 접목하는 방법을 도출하였으며, 적용 사례로서 기계 제조업체의 구매업무를 중심으로 품질경영시스템 구축방안을 제시하였다. 본 연구의 결과는 다음과 같다. 첫째, 정형화된 업무 체계를 갖추어 업무 담당자간 혹은 부서간의 업무 마찰을 줄이고 여러부서에서 발생하는 업부 DATA를 중앙집중식으로 공유하여 동일한 DATA의 수집과 작성에 중복성을 최소화하는 등에서 업무의 효과가 있는 것을 볼 수 있다. 둘째, ERP PACKAGE를 이용한 품질경영시스템(ISO 9000:2000/KS A 9000:2001)의 효과적인 추진 방안은 다음과 같다 1) 전환 규격의 충분한 이해가 요구된다. 2) 현재의 업무 프로세스를 파악한 후 ERP PACKAGE에서 제공하는 개선된 업무프로세스를 적용하는 것이 필요하다. 3) 개선된 업무 프로세스의 실행 결과를 ERP PACKAGE 모듈에서 품질기록으로 유지한다. 4) 새로운 품질경영 정보 시스템을 업무 전반에 적용하기 위한 기업인프라 구축과 프로세스에 대한 지속적인 개선이 요구된다. 본 연구에서는 ISO 9000:2000/KS A 9000:2001 개정 규격요구사항을 이해하고 ERP PACKAGE를 이용하여 최초로 개정규격을 적용하거나, 전환규격으로 품질경영시스템을 구축 시 좀더 효과적이고 효율적인 품질경영시스템을 구축하는데 업무지침으로 활용될 수 있을 것이다.의 수와 생존율면에서 볼 때 가장 적합한 것으로 사료되었다./TEX>개월 투여하게 되면 HDL 콜레스테롤 양이 현저히 증가하였으며, 총 콜레스테롤 양, 동맥경화지표, 중성지방, 유리지방산, 과산화지방은 현 저히 감소하였다.- 결론 - 홍삼과 진세노사이드는 사람과 흰쥐에 있어 과지혈증을 호전시켰다. 실험적으로 과지혈증을 유발시킨 흰쥐에서, 혈중 아포단백질, 지방단백질 및 프로스타글란딘 상호성을 개선시켰다.었다.xA_{2}$ synthetase 억제제인 imidazole의 효과와 유사하였다. 4. G-Re는 $1{\times}10^{-5}g/ml$ 이하의 농도에서는 효과가 없으나 $1{\times}10^{-4}g/ml$ 이상의 농도에서 농도의존적으로 유의성 있는 $PGE_{2},\;PGF_{2}{\alpha},\;TXB_{2}$의 생성억제와 함께 6-keto-$PGF_{1}{\alpha}$ 증가를 보였다. 이는 prostacyclin synthetase를 자극하는 serotonin의 효과와 같은 작용으로서 prostacyclin synthetase 억제제인 tranylcypromine에 대하여 길항효과를 보였다. 5. $TxB_{2}$생성억제 작용을 나타내는 ginsenoside들의 효과를 뒷받침하기 위하여 인삼 saponin 성분을 전처치한 patelet rich plasma에서 혈소판 응집시험 결과, ADP로 유도된 혈소판 응집반응에는 모든 인삼 saponin 성분들이 효과가 없었으나 arachidonic acid로 유도된 혈소판 응집반응에는 $G-Rb_{2}$, G-Rc, G-Re의 순으로 농도 의존적인 억제현상을 보였다. 이상의 결과와 같이 인삼 saponin 성분들은

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STUDIES OF GINSENG EXTRACT ON AGE-RELATED ENZYMES (고려인삼 추출물이 노화관련효소에 미치는 영향)

  • Cho Young Dong;Koo Bon Sook;Lee Song Jae
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.37-43
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    • 1984
  • 노화는 모든 다세포 유기물의 특징이다. 노화가 됨에 따라서 효소활성 및 면역반응의 감소와 과산화지질과 지방갈색물질의 축적, 효소와 염색질을 포함하는 단백질 구조의 변화, 호르몬계의 불균형 등이 일어난다. 그렇지만, 노화가 어떻게 일어나는지에 관하여는 현재까지 확실하지 않다. 본 연구진은 노화와 관련된 효소들에 관하여 연구를 하여 왔으며, 노화가 진행되는 동안의 효소의 활성을 유지시켜주거나, 또는 효소의 활성이 감소되는 것을 지연시켜 주는 물질을 찾고자 노력하였다. 그 가운데 하나로서, 고려인삼 추출물을 흰쥐에 기간별로 투여하여 효소활성의 차이, 열에 대한 안정성, 기질에 대한 친화력, 전기 영동 상의 이동성과 면역적인 반응을 대조군과 비교하였다. Glucose-6-phosphate dehydrogenase, 6-phosphog-luconate dehydrogenase, glutathione redutease, glutathion peroxidase와 같은 노화와 관련된 효소들의 활성을 고려인삼 추출물을 1개월간 흰쥐에 ($60{\~}80$g)투여하여 대조군과 비교 조사하였으나, 별 차이가 없었다. 그러나 고려인삼 추출물을 15개월간 투여하였을 때에는 이러한 노화관련 효소들의 활성이 급격히 증가함이 ($70{\~}200\%$) 관찰되었다. 예견된 바와 같이, 효소의 열에 대한 안정성과 기질에 대한 친화력도 증가함이 관찰되었다. 그러나 glucose-6-phosphate dehydrogenase의 경우에서 전기영동상의 차이 및 면역적인 반응은 대조군과 유사하였다. 이상의 결과는 고려인삼 추출물이 노화와 관련된 효소들의 활성이 감소되는 것을 지연시켜줄 수 있으며, 노화를 어느정도 지연시켜 줄 수 있음을 의미한다. 이와 같은 결과를 포함한 실험자료를 국제 인삼심포지움에서 발표할 것이다.$-tocopherol의 항 산화작용을 더욱 효과적으로 촉진 시킬 것으로 생각된다.-L(독성 호르몬-L)의 작용을 억제함으로서 암환자의 체중 감소를 방지하고, 식욕감퇴를 개선할것으로 생각된다.해되었으며, $Rb_{1}$은 장내의 효소와 tetracycline-resistantant bacteria에 의해 Rd와 2 종류의 미확인 물질로 분해되었다.xA_{2}$ synthetase 억제제인 imidazole의 효과와 유사하였다. 4. G-Re는 $1{\times}10^{-5}g/ml$ 이하의 농도에서는 효과가 없으나 $1{\times}10^{-4}g/ml$ 이상의 농도에서 농도의존적으로 유의성 있는 $PGE_{2},\;PGF_{2}{\alpha},\;TXB_{2}$의 생성억제와 함께 6-keto-$PGF_{1}{\alpha}$ 증가를 보였다. 이는 prostacyclin synthetase를 자극하는 serotonin의 효과와 같은 작용으로서 prostacyclin synthetase 억제제인 tranylcypromine에 대하여 길항효과를 보였다. 5. $TxB_{2}$생성억제 작용을 나타내는 ginsenoside들의 효과를 뒷받침하기 위하여 인삼 saponin 성분을 전처치한 patelet rich plasma에서 혈소판 응집시험 결과, ADP로 유도된 혈소판 응집반응에는 모든 인삼 saponin 성분들이 효과가 없었으나 arachidonic acid로 유도된 혈소판 응집반응에는 $G-Rb_{2}$, G-Rc, G-Re의 순으로 농도 의존적인 억제현상을 보였다. 이상의 결과와 같이 인삼 saponin 성분들은 arachidonic acid로부터 cyclooxygenase를

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Alteration of Vascular Reactivity in Cadmium-poisoned Rabbits (카드뮴 중독(中毒)에 의한 이곡혈관운동성(耳穀血管運動性)의 변동(變動))

  • Hong, Ki-Whan;Rhim, Byung-Yong
    • The Korean Journal of Pharmacology
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    • v.18 no.1
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    • pp.23-31
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    • 1982
  • 1) Experiments were undertaken to elucidate the mechanism which elevates the systemic arterial blood pressure by cadmium (Cd). 2) The mean arterial pressure and peripheral resistance of central ear artery in Cd-poisoned rabbit were significantly increased in comparison with those in control. 3) The vascular pressure response to electrical stimulation in Cd-poisoned group was less than that in control. However, in the former group it showed the supersensitivity to norepinephrine. 4) The response to electrical stimulation was diminished by sodium arachidonate in the ear artery, on the contrary, it was rather enhanced in the vessel of Cd-poisoned group. The responses in both groups were reduced by pretreatment with either $PGE_2\;or\;PGF_{2{\alpha}}$. 5) The response to electrical stimulation was not affected in control, but enhanced in Cd-poisoned group by pretreatment with indomethacin. 6) When the ear artery of control group was perfused with physiological salt solution (PSS) the response to electrical stimulation was not changed by indomethacin, it was much enhanced without affecting on the response to norepinephrine when $K^+-free\;PSS$, was used. These results demonstrate the evidence that the alteration of regulatory mechanism on the vessels was causally related to the elevation of arterial pressure and the increase in peripheral resistance in Cd-poisoned rabbits.

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Reproductive Monitoring and Estrus Induction Using Ultrasonography and Hormone Assay in Dairy Cows II. Differential Diagnosis and Treatment of Coexist of Cysts and Corpus luteum (초음파검사 및 호르몬검사에 의한 젖소 번식검진과 발정유도 II. 황체가 존재하는 난소낭종의 진단과 치료)

  • 오기석;박상국;김방실;고진성;신종봉;백종환;홍기강;문광식;임원호
    • Journal of Veterinary Clinics
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    • v.20 no.3
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    • pp.376-383
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    • 2003
  • To establish the differential diagnosis and treatment method in bovine ovarian cysts, specially ovarian cysts with corpus luteum, serum progesterone concentration, rectal palpation and ultrasonography for measuring the cystic wall thickness and diameter of cyst and corpus luteum were investigated from 1,188 dairy cows with ovarian cysts. The plasma progesterone concentrations were 0.3$\pm$0.4 (mean$\pm$SD) ng/ml in 629 cows with follicular cysts, 3.7$\pm$1.1 ng/ml in 431 cows with luteal cysts, and 3.8$\pm$1.2 ng/ml in 128 cows with coexist of ovarian cysts and corpus luteum, respectively. The cystic wall thickness by ultrasonography were 1.6$\pm$0.4 mm in 629 cows with follicular cysts, 4.2$\pm$1.5 mm in 431 cows with luteal cysts, and 1.6$\pm$0.6 mm in 128 cows with coexist of ovarian cysts and corpus luteum, respectively. The days from initial treatment to insemination in follicular cysts were 28.1$\pm$6.9 days in treatment of GnRH alone, 15.9$\pm$2.9 days in combination of GnRH and dinoprost, and 15.1$\pm$3.1 days in combination of GnRH and cloprostenol. The percentages of cows conceived within 100 days after initial treatment were 61 %, 68% and 73% in treatment of GnRH alone, combination of GnRH and dinoprost, and combination of GnRH and cloprostenol, respectively. The days from initial treatment to insemination in luteal cysts were 3.8$\pm$0.6 days in treatment of dinoprost alone and 3.8$\pm$0.7 in cloprostenol alone. The percentages of cows conceived within 100 days after initial treatment were 69.5% and 68.5% in treatment of dinoprost and cloprostenol, respectively. The days from initial treatment to insemination in coexist of cysts and corpus luteum were 3.7$\pm$0.7 days in treatment of dinoprost alone and 3.8$\pm$0.6 in cloprostenol alone. The percentages of cows conceived within 100 days after initial treatment were 87% and 84% in treatment of dinoprost and cloprostenol, respectively. These results suggest that the best choice for treatment agents in ovarian cysts were combination of GnRH and PGF$_2$$\alpha$ in follicular cysts, and the PGF$_2$$\alpha$ in luteal cysts and in coexist of cysts and corpus luteum, respectively. In conclusion, it is suggest that ultrasonography is useful diagnostic tool for diagnosis and selection of treatment remedy in cystic ovaries of bovine.

Monitoring the Sonographic Ovarian Dynamics and Pregnancy Rate in Cyclic Murrah Buffalo Cows Synchronized with Prostaglandin F2α

  • Harun-or-Rashid, Mohammad;Phulia, SK;Hasan, Mir Md. Iqbal;Musharraf, Mohammad;Bhuiyan, Uddin;Juyena, Nasrin Sultana;Sharma, Rakesh Kumar
    • Journal of Animal Reproduction and Biotechnology
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    • v.35 no.1
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    • pp.50-57
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    • 2020
  • The objective of this research work was to know ovarian dynamics and pregnancy rate of cyclic Murrah buffalo cows with induced estrus by administration of prostaglandin F2α (PGF2α) and timed artificial insemination (TAI) with frozen thawed semen. A total of 31 female buffaloes were selected for the study. The buffalos having matured CL observed by ultrasonography were given one intra muscular injection of cloprostenol 500 ㎍ and TAI was performed using frozen thawed semen of Indian Murrah buffalo bull. Results showed that 90.32% (significantly, at p < 0.05) cows explore the sign of heat after injection of PG and 67.85% (significantly, at p < 0.05) cows were become pregnant out of 28 inseminated (TAI) cows. In the 28 inseminated (TAI) cows, average number of smaller and larger size of follicles were non-significantly (p > 0.05) higher at day 3 post PG injection, but the medium size of follicles was nonsignificantly (p > 0.05) higher at PG injection. At day 3 post PG injection the diameter of follicles was significantly (p < 0.05) higher, but the diameter of CL was significantly (p < 0.01) lower compared at PG injection. At PG injection the diameter of largest follicle was non-significantly differences (p > 0.05) in between pregnant and non-pregnant cows. But at day 3 post PG injection it was significantly (p < 0.01) higher in pregnant cows compared to non-pregnant cows. The number of small, medium, and large follicles at PG injection and at day 3 post PG injection were non-significantly (p > 0.05) difference in between pregnant and non-pregnant buffalo cows. Finally, it is concluded that the CL was effectively regresses and induced the sign of heat in buffalo cows and after AI the cows were become pregnant with significant rate. The study will help to the veterinarian and researcher to know the efficacy of PG injection and AI for reproductive efficiency in buffalo cows.

Estrous Synchronization and Artificial Inseminationin in European Mouflon (Ovis gmelini musimon)

  • Yong, Hwan-Yul;Kim, Seung-Dong;Bae, Bok-Soo;Son, Chun-Soo;Son, Go-Tae;Jeon, Kang-Hee;Song, In-Jun;Kang, Shin-Keun;Gu, Dae-Chang;Lee, Joo-Hyung;Kim, Heon-Youl
    • Journal of Embryo Transfer
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    • v.24 no.4
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    • pp.271-274
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    • 2009
  • To establish a protocol of estrus induction and synchronization in European mouflon, we performed artificial insemination using frozen-thawed semen and exogenous hormones. CIDR was inserted into vaginas of four mouflons for 16 days. A day before removal of CIDR, PG 600 was injected intramuscularly. $PGF_2{\alpha}$ was injected when removing CIDR. Artificial insemination was cervically conducted with injecting LHRH 48 hours after CIDR withdrawal. Even though no pregnancy was confirmed, estrous signs were notified like open cervix, congestion of vaginal wall and discharge of cervical mucus. Further research in the wild sheep would be needed for development of artificial breeding methods and advancing sustainability of domestic zoos.

Efficacy of a Cue-Mate Intravaginal Insert and Injection of Prostaglandin $F_{a{\alpha}}$ for Synchronizing Estrus in Hanwoo Cattle

  • Cho, Sang-Rae;Kumar, Kuldeep;Yeon, Seong-Heum;Lee, Sung-Hwan;Kim, Ui-Hyung;Chung, Ki-Yong;Kim, Hyeon-Shup;Lee, Myeung Sik;Park, Chang-Seok;Yang, Byoung-Chul
    • Journal of Embryo Transfer
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    • v.29 no.4
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    • pp.321-325
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    • 2014
  • The present study was performed on farm animals to test the effectiveness of progesterone-releasing intravaginal device (Cue-Mate$^{(R)}$ 1.56 g) and injection of prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) for synchronization estrus in Hanwoo cattle. The cattle were at random stage of the estrus cycle. The cows were artificially inseminated at day 7 after Cue-Mate withdrawal, using commercial semen from Korean native bulls. There was a season effect on the estrus synchronization rate. It was higher in spring (94.3%) followed by winter (93.3%), autumn (90.4%) and summer (67.2%). In summary, The results of this study revealed that season has influences on estrus behavior of cattle with no significant effect on pregnancy rate. In summary, we suggest summer reproductive management to alleviate the effects of heat stress. It should be based on intensive cooling combined with hormonal treatment. Given that different subgroups of cows benefit differently from the treatments, selective hormonal administration should be considered.