• Journal of Acupuncture Research
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• v.17 no.2
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• pp.187-208
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• 2000

By the activation of ovary hormone, many morphological changes occur in the epithelial cell lines and muscle cells in rat uterus. These two cells in uterus are important to the implantation of embryo, maintaining pregnancy and starting parturition. One important change associated with the morphological change of these two cells in uterus is the change on prostaglandin(PG) metabolism. Its presence and synthesis in endometriurn and myometrium in uterus affects estrous cycle and the start of embryo implantation in uterus. It also performs as an important modulator in parturition. So the abnormally weak expression of PG causes difficulty during labor and over-expression causes pre-term labor. PG biosynthesis starts from either free or liberated arachidonic acids from membrane phospholipid by phospholipase. Such arachidonic acids are converted into PG catalyzed by Cyclooxygenase. Under normal physiological condition, Cyclooxygenase-1(COX-1) having 602 units of amino acids controls the synthesis of PG. It acts as a local hormone regulating vasomodulation of blood flow, flexible muscle movement, increasing the blood permeability and contributing the protective role in preserving integrity of the stomach lining and Cyclooxygenase-2 (COX-2) is induced by the inflammation, pregnancy and increased its expression until parturition. Lipid metabolite like PG is located in uterine and expression of COX-2 increased with pregnancy. Increased expression of COX proteins in epithelial cells and myometrial cells are told to increase the muscle contractility in uterus but decreased right after the labor in rat. It is a good sign indicating that COX proteins are deeply related to the start of labor. Currently, Several studies report the use of PG and COX-2 inhibitor as medication for controlled abortion or to prevent pre-term labor but they entail various side-effects. Our study proposed to suggest use of acupuncture as an another mediator to control abortion or pre-term labor without causing unnecessary side-effects by those medicines. Two acupuncture sites, LI-4 & SP-6 were selected due to their known efficacy. From the immunohistochemical staining of COX-2, normal expression of COX-2 protein in nonpregnant SD rat's uterus revealed that COX-2 protein was primarily detected in the lumina epithelial lining and in the epithelial cell lining contacting the stromal cells. High resolution optical microscopic scanning revealed distinguishable staining in the myometrial mucosa. LI-4 acupuncture administered nonpregnant rat's uterus showed strong expression for COX-2 in endometrium contacted with lumina epithelial lining of rat uterus and in myometrial mucosa. Stromal cells showed more staining than untreated nonpregnant rat's uterus and stronger staining in stromal cells contacting myometrial layer compared to untreated nonpregnant rat's uterus. SP-6 acupuncture administered nonpregnant rat's uterus showed weak expression for COX-2 in myometrial layers and stromal cells but no staining was visible in lumina epitheliai and glandular epithelial cells. Few stromal cells and myometrial mucosa were positively stained for COX-2. Pregnant SD rat's uterus was also immunostained for COX-2 expression after 18 days of pregnancy. Unlike to untreated nonpregnant rat's uterus, luminal epithelial cells were not positively stained for COX-2 but stronger staining for COX-2 was revealed in stromal cells. LI-4 acupunctured SD rat's uterus had very strong expression of COX-2 in luminal epithelial lining. Few stromal cells showed stronger positive COX-2 staining and myometrial layers also showed more expression than untreated pregnant rat. SP-6 acupuncture administered pregnant SD rat's uterus showed positive expression of COX-2 in epithelial cells of luminal mucosa layer but weaker than that of LI-4 acupuncture treatment's case. However, strong positive staining was revealed in stromal mucosa and myometrial layers. Virgin SD rat's uterus motility index during LI-4 acupuncture was 66.52 % (Prob〉T = 0.0197) compared to its motility before the acupuncture treatment but the motility index was slighdy elevated up to 79.58 % (Prob〉T = 0.1175) after the acupuncture. During the SP-6 acupuncture treatment for 30 minutes, uterus motility index was 90.52 % (Prob〉T = 0.1832) showing lesser decrement but consequently reached similar motility index decreasal to 79.95 % (Prob〉T = 0.0215) after the acupuncture treatment as LI-4 showed. LI-4 acupuncture tend to be a quick treatment to reducing the uterus motility in a virgin rat but eventually both two acupuncture administration created very similar reduction of uterus motility seeing the index after the both acupunctures. The uterus movement monitored during the LI-4 acupuncture administered for 30 minutes, Pregnant SD rat showed decreased motility down to 77.90 % (Prob〉 T = 0.0076) compared to uterus motility before the acupuncture and it continuously decreased down to 71.81 %(Prob〉T = 0.0214) after the removal of needle. The statistical analysis using paired t-test showed significance difference for both two motility indexs at =0.05. SP-6 acupuncture administered to pregnant SD rat also had similar pattern of decreasing uterus motility index down to 74.70 % (Prob〉T = 0.1730) during the initial 30 minutes acupuncture administration and it was continuously lowered to 71.52 % (Prob〉T = 0.0155) after the acupuncture. The paired t-test resuit for SP-6 suggest prompt response of uterus motility index to the SP-6 acupuncture treatment but consequently reached same level of inducing the motility reduction as LI-4 at =0.05 level.

• Journal of Environmental Health Sciences
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• v.31 no.3
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• pp.179-186
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• 2005

The purpose of this paper was to concisely review the practical changes in MeHg concentrations in fetus and offspring throughout gestation and suckling from our recent animal and human studies. In the animal study, adult female rats were given a diet containing 5ug/g Hg (as MeHg) for 8 weeks. Then they were mated and subsequently given the same diet throughout gestation and suckling. On embryonic days 18, 20, 22 and at parturition, the concentrations of Hg in the brains of fetus were approximately 1.5-2.0 times higher than those in the mothers. However, during the suckling period Hg concentrations in the brain rapidly declined to about 1/10 of that during late pregnancy. Hg concentrations in blood also decreased rapidly after birth. In human study, Hg concentrations in red blood cells (RBC-Hg) in 16 pairs of maternal and umbilical cord blood samples were compared at birth and 3 months of age after parturition. RBC-Hg in the umbilical cords was about 1.6 times higher than those in the mothers at parturition. However, all the infants showed declines in Hg concentrations throughout the breast-feeding period. RBC-Hg at 3 months of age was about half that at birth. Both the animal and human studies indicated that MeHg exposure to the fetus might be especially high but it dramatically decreases during the suckling period. Therefore, close attention should be paid to the gestation rather than the breast-feeding period to avoid the risk of MeHg to human infants.

• Toxicological Research
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• v.18 no.4
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• pp.401-409
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• 2002

Phthalate esters have possible effects on the endocrine system. Di-n-butyl phthalate (DBP) is one of the most commonly wed phthalic acid esters (PAEs). It is extensively wed as a plasticizer in elastomers, as a solvent for printing inks and resins, and as a textile lubricating agent. It is also present in the formulations of various cosmetic products. DBP has been identified as a reproductive toxicant in several animal species and also know as a endocrine disruptor. The objective of this study was to investigate the effect of DBP on developmental immune Junction wing rat pups as experimental animals. Timed-bred pregnant SD rats were orally dosed with 0, 250, 500, or 750 mg DBP/kg body weight once a day from gestational day (GD) 5 to 18 and postpartum day (PD) 3 to 18. On PD22, the dams and their pups were euthanized and examined for alteration in parameters associated to immune function. The results showed no significant changes in body weight, thymus weight, thymus and spleen cellularities, the polyclonal activation respones of splenocyte with ConA and LPS, and also the distribution of arterial blood cells and thymocyto subsets in both rat dam and pups. However DBP exposure on rat dam resulted in increases of liver weights of dam and their pups except 750 mg DBP/kg, and body and spleen weights in pups except 750 mg DBP/kg. On the other hands, distribution rates of CD8+ T cells at 500 mg DBP/kg and B cells at 750 mg DBP/kg among splenocyte subsets were significantly increased in rat pups, unlike dams. Reasons of these distribution alterations of CD8+ T cells and B cells in rat pups are under study.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.11 no.1
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• pp.33-40
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• 1981

The author studied on the effects of x-irradiation to the development of digital malformation in gestation rats. The time-matings occured between 6 p.m. and 8 a.m. and females with copulation. plugs at 8 a.m. were isolated and properly marked for evidence of copulation. The lower abdomen of mothers were exposed to x-irradiation on the 11½th day of gestation, the critical period developing digital malformation, respectively 100, 150, 200, 250, 300 and 350 rads. At 18½th day of post-conception total 50 pregnant females were dissected and the incidence of digital malformations were obtained. Rat embryos on the 12, 13, 14, 15, 16th day of gestation irradiated by 250 rads were examined for morphogenesis of digital malformation. Digital radiating lines were examined in water and histologically by H-E stain. Supra vital stain samples by Nile-blue sulfate in 37℃ normal saline were prepared for the observation of cell necrosis regions and morphogenesis of digits. The results obtained were as follows; 1. By x-irradiation on 11th day of gestation, digital malformations of Ectrodactylia, Syndactylia Polydactylia and Hematodactylia were developed. Ectrodactylia showed the effective relationship to the amount of irradiation, however Syndactylia ans Polydactylia did not. 2. By x-irradiation, cell necrosis of digital germ was appeared markedly, but in 48 hours after irradiation was depressed to the periphery of digital germ and in 72hours after irradiation was disappeared. Digital radiating line showed marked stage of malformation in 48hours after irradiation and continued to show the same amount of physiological cell necrosis as the compared control group in 72hours. after irradiaion. But in the Syndactylia, physiological cell necrosis was not able to be recognized. 3. Ectrodactylia induced by x-irradiation was considered as the direct resoult of cell necrosis of digital origin, however, Polydactylia and Syndactylia were considered as the resoult of some effect in repair process of x-irradiation damages.

• Journal of Pharmacopuncture
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• v.23 no.3
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• pp.165-172
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• 2020

Objectives: In the past few years, herbal medicines have gained popularity over synthetic drugs because of their natural source and minimal side effects which has led to a tremendous growth of phytopharmaceuticals usage. With the development of nanotechnology, it provides alternative approaches to overcome several limitations using nano-formulations. In spite of considerable quantity of antianemic preparations with different iron forms available, currently additives are used and represented in modern pharmaceutical market. Iron deficiency anemia is a major global public health problem which particularly affects pregnant women, children and elderly persons. The situation is complicated because of disadvantages and drug side effects from existing antianemic medicines. There is a great demand for the development of new antianemic preparations. Green synthesis of iron oxide nanoparticles, possess high potential in this field. Methods: Our study focuses on developing green synthesis of iron oxide nanoparticles (IONPs) of 10-50 nm with spherical shape where different dosages were used -1 mg/kg, 10 mg/kg and 100 mg/kg for exposure in Wistar albino female rats for 28 days. The toxicity was assessed using various parameters such as measurements of the rat body and organ mass, hematology, biochemical evaluation and histopathological examinations. Results: No significant differences were observed in body and organ weights. Hematological indices also indicated no significant differences whereas biochemical factors showed increase in levels of direct bilirubin and globulin of medium as well as high dose and SGPT levels were increased only in high dose. The major organs (heart, kidney and liver) showed histopathological alterations in 10 and 100 mg/kg whereas brain showed only in 100 mg/kg. Conclusion: The toxicity of IONPs was found to be more significant when the concentration was increased; however, low doses can be used for further investigation as an antianemic preparation.

• Journal of Nutrition and Health
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• v.23 no.6
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• pp.443-450
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• 1990

Pregnant rats were fed liquid diet to determine the influence of maternal ethanol intake on maternal and pup liver copper when dietary copper was low. The diets, which contained either 0.75(low) or 3.75(control)mg copper/1 with or without 30% of kcal from ethanol, were fed throughout gestation and the first 15 days of lactation. maternal calorie intake and body weight were unaffected by dietary treatment. Ethanol intake depressed maternal liver copper concentration only when diet copper was low(interactive effect P<0.05). Although ethanol intake depressed total pup liver copper concentration regardless of dietary copper level, the interactive effect observed in maternal liver was reflected incopper content of the pup liver metallothionein fraction eluted from a Sephadex G-75 column. The zinc content of metallothionein was inversely related to copper content of metallothionein. Results suggest that pregnancy and lactation is a special period to develop a copper deficiency when low copper intake and ethanol ingestion are combined not only in mothers but also in their offspring.

• Current Research on Agriculture and Life Sciences
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• v.4
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• pp.124-126
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• 1986

A teratogenecity study was carried out on SD rats administered antiemetic drug (components: diphenhydramine hydrochloride, caffeine, promethazine hydrochloride) at dose levels of 5, and 10ml/kg/day for a period of 11 days from day 7 to 17 of gestation. All of the pregnant females in each group were sacrificed on 20th day of gestation and their fetuses were examined. The incidences of external and skeletal anomalies were not significantly increased in the fetuses of any treated groups, and delayed ossification and resorptions in the treated groups were increased compared to these of the control group and mean number of corpus lutea on the treated groups were decreased compared to that of the control group.

• Journal of Embryo Transfer
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• v.13 no.3
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• pp.261-275
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• 1998

본 연구에서는 GnRH가 과배란 처치된 래트의 초기 난포기와 후기 난포기에서 난소기능에 어떠한 영향을 미치는지를 이해하기 위해서, 30IU PMSG와 10IU hCG로 전처치된 미성숙 래트에 있어서 배란반응, 배란 난자의 형태학적 이상 유무 및 핵 성숙도, 난소 중량, 난소의 조직학적인 변화 및 혈중 스테로이드 호르몬 (17$\beta$-estradiol, progesterone 및 testosterone) 농도에 대하여 GnRH agonist의 효과를 검사하였다. GnRH agonist는 PMSG 전처치 후 초기 난포기 (PMSG 투여 후 6시간부터) 또는 후기 난포기(PMSG 투여 후 54시간부터)에 4시간 동안 20분 간격으로 경정맥 카테타를 통해 혈관내로 투여하였다. 각 실험동물은 혈중 스테로이드 호르몬의 변화를 측정하기 위하여 PMSG 투여 후 54시간, 72시간에 혈액을 채취하고 72시간에 희생시켰다. PMSG로 전처치한 미성숙 래트의 초기 난포기에 GnRH agonist의 투여는 GnRH agonist를 투여하지 않은 군(대조군)에 비해 과배란 억제, 형태학적 비정상 배란난자의 증가, 난소 중량의 감소, 난포폐쇄의 증가 및 혈중 스테로이드 호르몬의 농도 감소가 보였다. 한편 후기 난포기에 GnRH agonist의 투여는 대조군에서의 반응과 전반적으로 유사하였다. 이상의 결과, PMSG 및 hCG 처치로 과배란된 래트의 초기 난포기에 GnRH agonist의 투여는 난소기능을 전반적으로 억제하지만, 후기 난포기에 GnRH agonist의 투여는 난소기능에 영향을 미치지 않았다.

• Journal of Environmental Health Sciences
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• v.33 no.4
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• pp.306-316
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• 2007

This study have a object to found out the effects of oriental herb medicine, Antaeeum, to dams of rats and their offsprings. The Antaeeum was savaged to female Sprague-Dawley rats at a dose of 5 mg/kg/day for 3 weeks during gestation periods. Dams of rat were sacrificed at 20th day of gestation, and were observed major internal and reproductive organs. Approximately live fetuses in the 20th days of gestation were selected randomly and examined with stereo microscopes. Others offsprings were fixed with 95% ethanol for skeletal examinations. The fixed fetuses were stained with alcian blue and alizarin red S to observe skeletal variations or malformations. Maternal body weight of Antaeeum treated dams have a tendency of increasing compared with control dams. There were no significant difference in internal and reproductive organs of weight or findings. The spleenic organ relative weight of treated dams were decreased compared with the control significaltly (p<0.05). There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But in the Antaeeum treated group showed lower early resorption rate than that of the control dams. Fetal body weight and number of fetus a dam at Antaeeum treated group were higher than that of control group. The fetuses of dams treated with Antaeeum didn't induced external malformations. Vertebral and sternal variations were observed in Antaeeum group, but compared with the control, those variations were not significant. The ossification numbers of rib, cervical, thoracic, and lumber were normal. Fetuses treated with Antaeeum to the dams showed no significant difference in the number of caudal vertebra (P>0.01). From these results, it can be concluded that Antaeeum showed no toxicity effects on maternal side especially on body weight, early resorption rate, and number of live fetuses. Also there were no significant changes on maternal organ weights except spleen, hematological data, reproductive organs. Although skeletal variations were examined at vertebra and sternum, this Antaeeum could not induced significant choses in bone malformation.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.