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Effect of ${\gamma}$-mangostin through the inhibition of 5-hydroxytryptamine$_{2A}$ receptors in 5-fluoro-${\alpha}$-methyltryptamine-induced head-twitch responses of mice

  • Nattaya Chairungsrie;Furukawa, Ken-Ichi;Takeshi Tadano;Kensuke Kisara;Yasushi Ohizumi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.170-170
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    • 1998
  • In order to discover new types of 5-hydroxytryptamine antagonists, we have devoted our attention to investigating naturally occurring compounds having anti-5HT activity in vitro. Recently, ${\gamma}$-mangostin [1,3,6,7-tetrahydroxy-2,8-bis(3-methyl-2-bytenyl)-9H-xanthen-9-one] from the fruit hull of Garcinia mangostana Linn has been shown to be a selective antagonist for 5-hydroxytryptamine$_{2A}$ receptors in smooth muscle and platelets. It is of interesting that y-mangostin which does not have a nitrogen atom, possesses marked 5-$HT_{2A}$ receptor blocking activity. The present study was undertaken to investigate the effects of ${\gamma}$-mangostin on central 5-HT receptors by using animal behavioural models. Intracerebronventricular injection of ${\gamma}$-mangostin (10-40n mol/mouse) inhibited 5-fluoro-${\alpha}$-methyltryptamin (5-FMT) (45 mg kg$^{-1}$, i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (5-HT-uptake inhibitor). Neither the 5-FMT- nor the 8-hydroxy-2-( di-n-propylamino )tetralin (5-HT$_{1A}$-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by ${\gamma}$-mangostin. The locomotor activity stimulated by 5-FMT through the activation of at-adrenoceptors did not alter in the presence of ${\gamma}$-mangostin. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. ${\gamma}$-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation and the binding of [$^3H$]-spiperone, a specific 5-$HT_{2A}$ receptor antagonist, to mouse brain membranes. Kinetic analysis of the [$^H3$]-spiperone binding revealed that ${\gamma}$-mangostin increased the $_{d}$ value without affecting the $B_{max}$ value, indicating the mode of the competitive nature of the inhibition by ${\gamma}$-mangostin. These results suggest that ${\gamma}$-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-$HT_{2A}$ receptors not by blocking the release of 5-HT from the central neurone. ${\gamma}$-Mangostin is a promising 5-$HT_{2A}$ receptors antagonist in the central nervous system.m.

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Interictal rCBF SPECT, MRI and Surgical Outcome of Intractable Temporal Lobe Epilepsy (난치성 측두엽간질의 발작간 뇌혈류 SPECT, MRI와 수술성과 비교)

  • Zeon, Seok-Kil;Joo, Yang-Goo;Lee, Sang-Doe;Son, Eun-Ik;Lee, Young-Hwan
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.3
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    • pp.307-312
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    • 1994
  • Interictal single photon emission computed tomography of regional cerebral blood flow (rCBF SPECT) in 18 intractable temporal lobe epilepsy patients(8 male and 10 female patients: average 23.5 years old) were compared with 2.0 T magnetic resonance imaging (MRI). And surgical outcome was analysed with the findings, symptom duration and lateralization of temporal lobe. Preoperatively rCBF SPECT was done in all 18 patients with intravenous injection of 740 MBq 99mTc-HMPAO. MRI was also done preoperatively in 13 patients. Surgical outcome was classified by Engel's outcome classification(four-part classification recommended at the first Palm Desert conference). rCBF SPECT detected correctly lateralising abnormality of temporal lobe hypoperfusion in 13/18(72.2%), contralateral temporal lobe hypoperfusion in 2/18(11.1%) and showed no def-inite abnormality in 3/18(16.7%). The positive predictive value of unilateral temporal lobe hypoperfusion was 87%. MRI detected correct localising abnormality in 8/13(61.5%), such as hippocampal atrophy(7/13), asymmetric temporal horn(6/13), anterior temporal lobe atrophy(1/13), increased signal intensity from hippocampus(1/13) and calcific density(1/13), and no abnormal finding was noted in 5/13(38.5%). There was no false positive findings and the positive predictive value of MRI was 100%. Only 2 cases showed same lateralization findings in rCBF SPECT and MRI. There was no significant correlation between symptom duration and no abnormal findings on SPECT or MRI. Surgical outcome showed class I in 15/18(83.3%), and class II in 2/18(11.1%). One case of no abnormal finding in both SPECT and MRI showed class III surgical outcome. No class IV surgical outcome was noted. Surgical outcome, lateralization of epileptic focus in temporal lobe and abnormal findings in rCBR SPECT or MRI were not significantly correlated.

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Comparison of Pregnancy Rates by Intrauterine Insemination after Ovulation Trigger with Endogenous LH Surge, GnRH Agonist or hCG in Stimulated Cycles (인공수정시술주기에서 내인성 LH, GnRH Agonist 및 hCG를 이용한 배란유발후 임신율의 비교연구)

  • Lee, Jong-In;Hur, Young-Mun;Jeon, Eun-Suk;Yoon, Jeong-Im;Jung, Goo-Sung;Hong, Ki-Eon;You, Seung-Hwan;Lee, Hyeon-Sook;Hong, Jeong-Eui;Lee, Ji-Sam
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.3
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    • pp.389-398
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    • 1999
  • Objective: This study was designed to evaluate the effects of endogenous LH surge, GnRH agonist (GnRH-a) or human chorionic gonadotropin (hCG) as ovulation trigger on pregnancy rate by intrauterine insemination (IUI). Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days starting on the third day of the menstrual cycle followed by human menopausal gonadotropin (hMG) for ovulation induction. Follicles larger than >16 mm in diameter were present in the ovary, frequent LH tests in urine were introduced to detect an endogenous LH surge. Final follicular maturation and ovulation were induced by GnRH-a 0.1 mg (s.c.) or hCG $5,000{\sim}10,000$ IU (i.m.) administration except natural ovulation. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: There were no differences in age, duration of infertility and follicle size, but more ampules of hMG were used in GnRH-a group compared to hCG 10,000 IU treated group (p<0.05). Lower level of estradiol ($E_2$) on the day of hCG or GnRH-a injection was observed in hCG 10,000 IU group than other treatment groups (p<0.01). The overall clinical pregnancy rate was 19.8% per cycle (32/162) and 22.2% per patient (32/144). Pregnancy rate was higher in natural-endogenous LH surge group (37.5%, 9/24) than GnRH-a (18.8%) or hCG treated group (20.9% & 13.9%), but this difference was not statistically significant. No patient developed ovarian hyperstimulation. Abortion rate was 22.2% (2/9) in hCG 5,000 IU group. Delivery or ongoing pregnancy rate was 37.5% (9/24), 18.8% (3/16), 16.3% (7/43) and 13.9% (11/79) in endogenous LH surge, GnRH-a, hCG 5,000 IU and hCG 10,000 IU treatment groups, respectively. Conclusion: These results support the concept that use of natural-endogenous LH surge in stimulated cycles may be more effective to obtain pregnancies by IUI than GnRH-a or hCG administration.

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Alterations of Cerebral Metabolic Activation Following Electro-Acupuncture Stimulation on ST36 and LR3 Acu-Points in Rats (흰쥐의 족삼리 및 태충 전침자극에 따른 뇌대사활성의 변화)

  • Sohn, Young-Joo;Jung, Hyuk-Sang;Ku, Ja-Seung;Won, Ran;Kim, Yong-Suk;Park, Young-Bae;Sohn, Nak-Won
    • Journal of Acupuncture Research
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    • v.19 no.1
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    • pp.159-174
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    • 2002
  • Objective : The meridian theory in oriental medicine explains that each acu-point has a characteristic functional effect. It will be supposed that an acupuncture stimulation on different acu-point evokes different activation on different areas in the central nervous system(CNS) according to the meridian theory. On this supposition, our group tried the semi-quantitative [14C]2-deoxyglucose([14C]2-DG) autoradiography on the acupuncture stimulation to the hindlimb acu-points of Sprague-Dawley rats. Methods : A venous catheter for the intravenous administration of isotope was equipped in the right external jugular vein on 3 days prior to the [14C]2-DG study. On the day of the study, two acupuncture needles were inserted into the ST36(Zusanli) or LR3(Taichong) on the left hindlimb. Electro-acupuncture stimulation (2 Hz, 5 ms, 1~3 mA, 15 minutes) started just before the i.v. injection of [14C]2-DG ($25{\mu}Ci/rat$). The brain and the spinal cord were removed and processed for the [14C] 2-DG autoradiography. Results : The EA stimulation on ST36 reveals over 120% metaboilc activation in Arcuate nucleus, Anterior pretectal nucleus, Dorsal cochlear nucleus, Interposed cerebellar nucleus, and Nucleus of Darkschewitsch. The EA stimulation on LR3 reveals over 120% metaboilc activation in Lateral habenula nucleus, Medial vestibular nucleus, Ventromedial thalamic nucleus, Anteroventral thalamic nucleus, Anterior cingulate cortex, Dentate gyrus, Antero cortical amygdaloid nucleus, Anterior pretectal nucleus, and Dorsal tegmental nucleus compared with the non EA stimulation control group. Conclusion : These results demonstrate that the different acu-points evoke the different activations in brain areas. And with this functional brain mapping study, a new scientific elucidation for the basis of the acupuncture-meridian theory in oriental medicine through differences of activated area in CNS according to the each acupuncture point.

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Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis

  • Han, Jiahong;Dai, Min;Zhao, Yan;Cai, Enbo;Zhang, Lianxue;Jia, Xiaohuan;Sun, Nian;Fei, Xuan;Shu, Hui
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.291-299
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    • 2020
  • Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1, Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G2/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

Effects of Ginseng Saponins in Energy Metabolism, Memory, and Anti-neurotoxicity

  • Wang Lawrence C.H.;Lee Tze-fun
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.55-65
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    • 2002
  • Ginseng has been used as a key constituent in traditional medicine prescriptions for centuries. Other than its well-known anti-stress and adaptogenic properties, ginseng has also been shown to be very effective in treating age-related deterioration in metabolic and memory functions. Although it is generally believed that the saponin (GS) fraction of the ginseng root accounts for the bioactivity of ginseng, a direct demonstration on which ginsenoside does what is still generally lacking. In the past decade, our laboratory has endeavored to identify the active GS components involved in energy metabolism, memory, and anti-neurotoxicity. To examine the ergogenic effects of GS in enhancing aerobic capacity, rats were subjected to either severe cold ($40^{\circ}C$ under helium-oxygen, two hours) or exercise workload $(70\%\;VO_{2}max,$ to exhaustion). Acute systemic injection (i.p.) of ginseng GS (5-20 mg/kg) significantly elevated both the total and maximum heat production in rats and improved their cold tolerance. However, pretreating the animal with the optimal dose (10 mg/kg) of GS devoid of $Rg_1\;and\;Rb_1$ failed to elicit any beneficial effects in improving cold tolerance. This indicates that either $Rb_1\;and/or\;Rg_1$ may be essential in exemplifying the thermogenic effect of GS. Further studies showed that only pretreating the animals with $Rb_1(2.5-5\;mg/kg),\;but\;not\;Rg_l,$ resulted in an increase in thermogenesis and cold tolerance. In contrast to the acute effect of GS on cold tolerance, enhancement of exercise performance in rats was only observed after chronic treatment (4 days). Further, we were able to demonstrate that both $Rb_1\;and\;Rg_1$ are effective in enhancing aerobic endurance by exercise. To illustrate the beneficial effects of GS in learning and memory, a passive avoidance paradigm (shock prod) was used. Our results indicated that the scopolamineinduced amnesia can be significantly reversed by chronically treating (4 days) the rats with either $Rb_1\;or\;Rg_1$ (1.25 - 2.5 mg/kg). To further examine its underlying mechanisms, the effects of various GS on ${\beta}-amyloid-modulated$ acetylcholine (ACh) release from the hippocampal slices were examined. It was found that inclusion of $Rb_1$ (0.1 ${\mu}M$), but not $Rg_1$, can attenuate ${\beta}-amyloid-suppressed$ ACh release from the hippocampal slices. Our results demonstrated that $Rb_1\;and\;Rg_1$ are the key components involved in various beneficial effects of GS but they may elicit their effects through different mechanisms.

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Effects of Prunellae Spica Extract on LT4-induced Hyperthyroidism in Rats through the Regulation of Heat and Cold Imbalance (하고초추출물의 갑상선기능항진증 랫트모델에서의 한열조절작용에 의한 개선효능 연구)

  • Kang, An Na;Kang, Seok Yong;Meng, Xianglong;Ma, Junnan;Park, Jong Hun;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.33 no.4
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    • pp.77-85
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    • 2018
  • Objective : This study was intended to examine the effects of water extract of Prunellae Spica (PS), which is a herb with 'cold' nature based on hot and cold theory of traditional Korean medicine. Methods : Hyperthyroidism was induced in SD rats by LT4 (0.5 mg/kg, i.p.) daily for four weeks. After 2 weeks of LT4 injection, rats were divided randomly into four groups; normal, LT4-induced hyperthyroid control, PS extract (500 mg/kg, p.o.)-treated group, and propylthiouracil (PTU, 10 mg/kg, s.c.)-treated positive group. After 2 weeks of drug treatment, all rats were sacrificed and harvested blood samples and thyroid tissues. The changes of body weight, food and water intake, and body temperature were measured weekly. Serological markers were analyzed in sera using an enzyme-based assay, and thyroid tissues were stained with Hematoxylin & Eosin (H&E). Brain and dorsal root ganglion (DRG) tissues were isolated and analyzed the expression of transient receptor potential (TRP) channels by Western blot. Results : PS extract administration attenuated the loss of body weight and the increase of body temperature in LT4-induced hyperthyroidism rats. PS extract increased the level of thyroid stimulating hormone (TSH) and decreased tiiodothyronine (T3) and tetraiodothyronine (T4). In action mechanism, PS extract regulated the expression of transient receptor potential channel subfamily V member 1 (TRPV1) and transient Receptor Potential channel subfamily M member 8 (TRPM8), the thermoregulators. Conclusion : To conclude, PS extract can improve the symptoms of hyperthyroidism through regulation of the thyroid hormones imbalance and thermoregulation via TRP channels.

STUDY OF THE EFFECT OF COMPREHENSIVE NURSING CARE ON THE ADJUSTMENT OF CHILDREN TO HOSPITALIZATION (유.소아를 위한 포괄적 간호가 그들의 병원생활 적응에 미치는 영향에 관한 연구)

  • 이자형
    • Journal of Korean Academy of Nursing
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    • v.3 no.3
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    • pp.97-110
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    • 1973
  • The goal of modern nursing is to provide comprehensive nursing care to patients. If comprehensive nursing care to children (within the hospital setting) is to be provided, consideration of the stage of growth and development of the child is especially important. From clinical observation, it appeared that nurses often disregarded individual requirements of children in giving nursing care. Therefore, the purpose of this study is to show that comprehensive nursing care which is based on an understanding of the growth and development of the child contributes to both the child and the mother's adaptability to the child's hospitalization. Method: Sixty children, three to three year of age, hospitalized at the Yonsei University Pediatric Ward ware studied. From April 1, 1973 to May 5, 1973, children admitted to the hospital were assigned to either an experimental or a compare groups. There were 30 children in each group. The sex and age of the children in each group was similar. In both groups were more male than female children. In the experimental group, each mother stayed with hot child continuously during his hospitalization. In the compare groups, the mother or some other member of the family stayed with the child. Each day on the child's admission the investigator visited the ward from 1-2 P.M. to 9-10 P.M., in order to provide comprehensive care for the experimental -group. The assistance given the nurses by the investigator was in the form of conferences regarding care and in giving direct care to the child and his mother. The compare group of children received nursing care as usually provided by the hospital. The instruments used to obtain the data for analysis were as follows: 1. The fear and anxiety reaction of the child was recorded by observation of the investigator for four areas: 1) separation from parent and relatives 2) reaction to Doctor and Nurse with white gowns 3) reaction to nursing care 4) reaction to injection and tests, etc. 2. Regression in area of eating, sleeping, and elimination were recorded by the investigator by questioning the mother and by observation. 3. Adaptability to the hospitalization was recorded by direct questioning of the children for areas of emotional and social adjustment. For children older than 3 years of age or children not seriously ill, using the simple I. Q. test this was possible for only 35 of the total 60 children. Result: 1. 55 percents of the total 60 children had been prepared by their parents for hospitalization. The children who had received prior preparation accepted hospitalization more readily than those who had received no preparation. (χ²=4.6 Ρ<0.05) 2. On admission 31.7 percent of the children expressed verbal fear of their discase or treatment. 25 percent felt that the disease was due to their mistake. 3. There was a significant difference in the reaction of the child to separation from the parent or relatives between the two groups. The experimental groups showed less anxiety due to separation than the compare group. (χ²=4.34 Ρ<0.05) In both groups there was less anxiety due to separation among school age (6-12 years) children than among preschool age (3-5 years) children. (χ²=9.22 Ρ<0.05) 4. More than half of the children in both groups reacted with fear and avoidance to doctor and/or nurses wearing white gowns. (χ²=0.06 Ρ<0.05) 5. The experimental group reacted more favorably to nursing in general than the compare group. (χ²=4.8 Ρ<0.05) 6. There was no difference in the fear and refused reaction to special tests and/or such as X-rays and injections, etc. between the groups. (χ²=3.77 Ρ<0.05) 7. More children in the compare group showed regressive tendencies in eating, sleeping, and elimination habits than in experimental groups. (χ²=2.3 Ρ<0.05 χ²=3.88 Ρ<0.05 χ²=4.9 Ρ<0.05) 8. There was a significant difference in the adaptability to hospitalization between the two groups. The experimental groups adapted more readily. (χ²=2.02 Ρ<0.05) 9. For children who had higher I.Q. s the adaptability to hospitalization was better regardless of the group. (χ²=5.03 Ρ<0.05) However, because of the small number of cases (60), this finding cannot be extrapolated without further verification. The date demonstrates that there was a greater adaptability to hospitalization by the child when comprehensive nursing care was given. By planning care and applying knowledge of growth and development to meet, nurses are in a position to prevent some of the psychological trauma associated with hospitalization.

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Effect of Multiple Superovulation and Parity on Embryo Production in Hanwoo (한우의 반복 과배란 및 산차가 수정란 생산에 미치는 영향)

  • Choi S. H.;Ryu I. S.;Son D. S.;Cho S. R.;Han M. H.;Kim H. J.;Choe C. Y.;Kim Y. K.
    • Journal of Embryo Transfer
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    • v.20 no.2
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    • pp.185-190
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    • 2005
  • This study was performed to investigate the effects of multiple superovulation and parity on embryo production in Hanwoo cows. Donors were superovulate 4 times $1\~2$ months interval and inserted CIDR plus (with the capsule of estradiol benzoate 10mg) on Day 10 from standing heat for 9 days and injected 2.5ml FSH (Antorin R-10) 2 times in a day on 6th day to 10th day from insertion of CIDR and the doses of FSH were decreasing 0.5ml on every 2 times. On 3th day of FSH injection, 25ml $PGF_2{\alpha}$ were injected i.m. and on 4th day, CIDR was removed. After 2 days from removing CIDR, AI was performed 2 times 12 hour apart with 2 straws of Korean Proved frozen Semen and simultaneously 200ug/ml GnRH was injected and embryos were recovered on 7th day from Al. The response rates of superovulated donors were $85.7\%,\;90.5\%,\;62.5\%,\;100\%$ from 1 to 4 times of superovulation, respectively. There were significant differences among No. of superovulation times (P<0.05). The results of transferable embryos were 3.7, 3.4, 3.4, 5.7 from 1 to 4 times of superovualtion, respectively. There were no differences among No. of superovulation times. The results of transferable embryos were 2.5, 3.0, 5.3, 3.0, 3.4 form heifer, first born to 4 the born, respectively. There were significant differences among the parities of donors (P<0.05). These results suggested that even 4 times of superovulations of Hanwoo donors could be able to recover transferable embryos, it might be used the donors maximally and improved the adaptation of embryo transfer to farms safely.

Effects of Milk Production, Postparient Days or Seasons on In Vivo Embryo Production by Superovulation in Holstein Cows (유우의 과배란 처리에 있어서 산유량, 분만 후 처리시기 및 계절이 체내수정란 생산에 미치는 영향)

  • Lim, Kwang-Taek
    • Journal of Embryo Transfer
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    • v.24 no.1
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    • pp.33-37
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    • 2009
  • Multiple ovulation and embryo transfer (MOET) has the potential to increase the rates of genetic improvement in cattle. Thus this study was performed to investigate several factors influencing in vivo embryo production in Holstein cattle under field conditions. The donors were superovulated with Folltropin-V and $PGF_2{\alpha}$ combination method. From Day 10 onward, donors were superovulated by i.m., twice daily, administration of 400mg Folltropin-V given in a series of decreasing doses over a 4-day period: on the first day, 3.5ml; on the second day, 3.0ml; on the third day, 2.0ml; and on the fourth day, 1.5ml (20ml in total, equivalent to 400mg of NIH-FSH-P1). Estrus was induced by i.m. administration of 25mg prostaglandin $F_2{\alpha}$ on the sixth and seventh of FSH treatment. Estrus detection was performed twice daily beginning 24h after the first prostaglandin $F_2{\alpha}$ injection. Donor cows were artificially inseminated 12 and 24 h after first standing estrus with semen from a proven Holstein sire. Embryos used in this study were recovered Day 7.5 of the cycle (Day 0: first standing estrus). From 195 superovulated dairy cows, 2,104 eggs were recovered, of which 1,172 were classified as transferable embryos based on morphological evaluation of quality. The results are summarized as follows: 1. The numbers of recovered and transferable embryos did not significantly differ among the capacity of milk production that were < 10,000kg/305days (group 1), $10,000{\sim}12,000\;kg$/305days (group 2) or > 12,000kg/305 days (group 3) (p>0.05, Table 1). 2. No differences in the numbers of recovered and transferable embryos were found among the donor's postparient days (p>0.05, Table 2). 3. Also, the numbers of recovered and transferable embryos of each superovulation seasons did not significantly differ among the four groups (p>0.05, Table 3).