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Supplementing punicalagin reduces oxidative stress markers and restores angiogenic balance in a rat model of pregnancy-induced hypertension

  • Wang, Yujue;Huang, Mengwei;Yang, Xiaofeng;Yang, Zhongmei;Li, Lingling;Mei, Jie
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.4
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    • pp.409-417
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    • 2018
  • Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (n=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p<0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.

Effects of carbendazim on DNA, gene and chromosome (살균제 carbendazim이 DNA, 유전자 및 염색체에 미치는 영향)

  • Lee, Je-Bong;Sung, Pil-Nam;Jeong, Mi-Hye;Shin, Jin-Sup;Kang, Kyu-Young
    • The Korean Journal of Pesticide Science
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    • v.8 no.4
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    • pp.288-298
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    • 2004
  • Benzimidazole pesticide carbendazim that is effective against a wide range of fungal plant pathogens is a protective, eradicant, and systemic fungicide. For genetic toxicity evaluation of carbendazim on DNA, genes and chromosome, were investigated with chromosome aberration, bacterial reverse mutation, micronucleus test in mouse born marrow and DNA damage assay by single cell microgel electrophoresis. Substitution and frameshift mutation were not induce at variable concentration of carbendazim on Ames test with or without rat liver microsomal activation. For the result of chromosome aberration test, numerical changes of chromosome were detected at the concentrations higher than $4.0{\mu}g/m{\ell}$, but structural aberration was not induced. Positive control, Mitomycin-C and captafol made a structural aberration, but numerical change of chromosome did not appear. In the micronucleus test for mouse born marrow, carbendazim was negative, but was weak positive in DNA damage assay by single cell microgel electrophoresis because of increased DNA moving length of 20% to control.

A 90-day Safety Study (Repeated-Dose Oral Toxicity Study) of Genetically Modified ${\beta}$-Carotene Biofortified rice in Sprague-Dawley Rats (SD 랫드에서 베타카로틴강화미의 90일 반복투여 경구독성시험)

  • Park, Soo-Jin;Jeong, Mi-Hye;Lee, Si-Myoung;Kim, Mi-Kyoung;Park, Kyung-Hun;Park, Jae-Yup
    • The Korean Journal of Pesticide Science
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    • v.15 no.3
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    • pp.278-288
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    • 2011
  • This study was conducted to evaluate the safety of ${\beta}$-carotene biofortified rice, a genetically modified organism (GMO) developed by Rural Development Administration. ${\beta}$-carotene biofortified rice were exposed on Sprague-Dawley rats for 13 weeks. All rats survived until the end of the exposure period. There were no biologically significant differences in body weight, feed and water consumption, weight gains and feed efficiency. There were no clinical signs of toxicity attributable to exposure to GM rice. Mild decreases in AST, ALT, TG levels were observed in Group II (25% GM rice (w/w) and Group III (50% GM rice (w/w), both in females and males. Results of histopathological changes treated with the ${\beta}$-carotene biofortified rice had no significant differences between the control and treatment groups. Based on these results, we deemed that genetically modified ${\beta}$-carotene biofortified rice was as safe as conventional rice.

Nerve Regeneration Using a Vein Graft Conduit filled with Hyaluronic Acid in a Rat Model (흰쥐 모델에서 하이알루론산을 채운 정맥도관의 신경재생에 관한 연구)

  • Suh, Bo Ik;Kim, Sang Woo;Chung, Ho Yun;Kim, Il Hwan;Yang, Jung Dug;Park, Jae Woo;Cho, Byoung Chae
    • Archives of Plastic Surgery
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    • v.34 no.3
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    • pp.279-284
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    • 2007
  • Purpose: The vein graft was considered as a useful conduit for nerve defect. But the problem is that it might be collapsed in long vein graft state. A new experimental model using vein graft filled with hyaluronic acid was considered. Methods: Thirty rats were used for the experimental animal. In group I, one side of the femoral nerve was exposed and a segment was removed about 15mm. The neural gap was connected with nerve graft. In group II, the nerve gap was connected with vein graft only. In group III, the nerve gap was connected with vein graft filled with hyaluronic acid. A walking track analysis was made periodically for 2 months and NCV(nerve conduction velocity) was executed at the end of the experiment. And morphologic studies were also done for all groups Results: In a walking track analysis, the toe-spread was widen and the foot-length was lengthened. The recovery of the toe-spread and foot length was checked 2 weeks interval, periodically for two months. The SFI (sciatic function index) was $-52.5{\pm}8.2$ in group I, $-68.1{\pm}4$ in group II, $-55.3{\pm}7.9$ in group III. In electrophysiological study, NCV(nerve conduction velocity) was $26.71{\pm}3.11m/s$ in group I, $17.94{\pm}4.35m/s$ in group II, $25.69{\pm}2.81m/s$ in group III. The functional recovery in group I and III was superior to that the group II statistically(p < 0.05) Under electromicroscopic study, the number of the myelinated axons were $1419.1{\pm}240$ in group I, $921.7{\pm}176.8$ in group II, $1322.2{\pm}318$ in group III. The number of the myelinated axons were much more in group I and III than group II statistically (p<0.05). Conclusion: This study suggested that the vein graft filled with hyaluronic acid is more effective than vein graft only for the conduit of the nerve gap. It was thought that the technique could be used in clinical cases with nerve defects as an alternative method to classical nerve grafts.

Comparative efficacy of silver containing dressing materials to Staphylococcus aureus and Pseudomonas aeruginosa on infected full thickness skin wound in the rat (흰쥐의 감염된 전층피부결손에서 은 함유 드레싱제제의 Staphylococcus aureus 및 Pseudomonas aeruginosa 균주에 대한 효과의 비교)

  • Lee, Jong Hoon;Kim, Dong Gu;Lee, Won Mi;Chae, Jeong Don
    • Archives of Plastic Surgery
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    • v.36 no.4
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    • pp.372-379
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    • 2009
  • Purpose: The purpose of this study was to compare the effect on antibacterial activities and wound healing effect of silver containing dressings with which of Betadine against Staphylococcus aureus and Pseudomonas aeruginosa. Methods: One full thickness skin defects in rats(n=72) were developed on the back and were given rise to infection with S. aureus(n=36) and P. aeruginosa(n=36). The 72 mice were divided into 6 groups : Acticoat$^{(R)}$, Aquacel$^{(R)}$-Ag, Medifoam silver$^{(R)}$, Polymen silver$^{(R)}$, Ilvadon$^{(R)}$ and Betadine(control group) dressing groups. Five silver containing dressings and Betadine were assesed on infected wound. Measurement of wound size change, bacterial colonies count and histologic findings was applied. Antibacterial activity was analyzed with bacterial restricted zone in Mueller Hinton agar. Results: On S. aureus, wound size was more decreased in all treated groups as compared with betadine, however Ilvadon$^{(R)}$ was less decreased on P. aeruginosa. In histologic findings, experimental group showed more effective findings than others on S. aureus, however on P. aeruginosa, which was showed similar. Acticoat$^{(R)}$ was best effective in wound healing against S. aureus and P. aeruginosa. The bacterial colonies count was increased in all treated groups except Acticoat$^{(R)}$ as compared with the control group on S. aureus, which was decreased in Acticoat$^{(R)}$ and Ilvadon$^{(R)}$ group on P. aeruginosa. There were not statistical differences. The restricted zone was shown in Mueller - Hinton agar of all groups except Medifoam silver$^{(R)}$ group on S. aureus, which was shown of all groups on P. aeruginosa. There were statistical differences. Conclusion: This study suggests that silver containing dressings may have not better potential than Betadine in assisting management of wounds at risk of infection on S. aureus and P. aeruginosa. However, which have better antibacterial activity on S. aureus and P. aeruginosa.

Diagnosis of fibroadenoma using radiolabeled bladder cancer specific peptide

  • Ha, Yeong Su;Kwak, Wonjung;Lee, Hwa Young;Lee, Byung-Heon;Hong, Il-Hwa;Jeong, Kyu-Shik;An, Gwang Il;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.1 no.1
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    • pp.38-45
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    • 2015
  • Most tumors are believed to overexpress several receptors, and small peptides targeting these receptors were developed for diagnosis and tumor therapy during past decade. Here we report that fibroadenoma can be visualized by bladder cancer specific peptide. A 9-mer bladder cancer specific peptide, which was discovered from the phage display method, was synthesized by peptide synthesizer, and additional tyrosine was conjugated at the N-terminal for radioiodination (Y-BP). Y-BP was radiolabeled with $^{131/124}I$ using Iodogen tube. The rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine for 8 weeks was allowed to grow until large size tumor was developed under axilla. The tumor model was microPET imaged sequentially using [$^{18}F$]FDG and radioiodinated $^{124}I-Y-BP$. The tumor was excised and examined by immunostaining studies. Radioiodinated $^{124}I-Y-BP$ was purified using fast protein liquid chromatography (FPLC) in > 90% radiochemical purity. The whole tumor was well visualized by [$^{18}F$]FDG with several intense focal uptake within tumor. The tumor was also clearly seen with $^{124}I-Y-BP$ at 4 h post-injection, and to our surprise the tumor uptake of $^{124}I-Y-BP$ lasted up to three days. The tumor was diagnosed histologically as a fibroadenoma derived from mammary gland. In conclusion, the bladder cancer specific peptide showed the good potential as a new radiotracer for the detection of breast fibroadenoma.

Fine Structure on the Epidermis of the Scalp of the Head-Irradiated Rats (방사선 조사를 받은 흰쥐 머리피부 표피층의 미세구조)

  • Ko, Jeong-Sik;Kim, Jae-Ho;Yang, Nam-Gil;Ahn, E-Tay;Park, Kyung-Ho;Kim, Jin-Gook
    • Applied Microscopy
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    • v.24 no.2
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    • pp.63-77
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    • 1994
  • This experiment was performed to study the morphological responses of the epidermis of the rat scalp, following X-ray irradiation. Male rats were divided into normal and experimental groups. Rats anesthetized with sodium thiopental, were exposed only on their head areas with a single dose of 3,000rads or 6,000rads, respectively. Radiation was produced by Mitsubishi Linea Accelerator ML-4MV at the speed of 200rads/min. The target distance was 80cm. Animals were sacrificed on six hours, two days and six days following irradiation. By the perfusion fixation through the heart, rats were fixed with 1% glutaraldehyde-1% paraformaldehyde solution. Pieces of the tissue taken from the scalp were refixed in 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide, and embedded within araldite mixture. The sections were cut on a LKB-V ultratome, stained with uranyl acetate and lead citrate, and were observed with JEM 100CX-II electron microscope. The results were as follow; 1. Six hours after exposure to 3,000rads of X-ray. Disrupted intercellular spaces, within which some amorphous materials were filled, disrupted mitochondria, and vacuoles in the keratinocytes were frequently observed, but six days after exposure to 3,000rads of X-ray, Morphology of the keratinocytes was generally restored. 2. Many of the morphological changes were seen on the six days after exposure to 6,000rads of X-ray. 3. Widened intercellular spaces and thickened dense plaques of the desmosomes were frequently observed after exposure to 6,000rads of X-ray. 4. In the experimental groups, the Langerhans and the Merkel cells were damaged, similarly to the keratinocyte. Above results suggest that head irradiation with the dose of 3,000rads temporarily damaged the epidermis of the scalp, though most of the structures recover within six days, whereas with the dose of 6,000rads it severely damaged the epidermis without showing any recovering tendency.

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Effects of Chitosanoligosaccharide on the Hepatotoxicity in Cadmium-treated Mice (키토산올리고당이 카드뮴을 투여한 생쥐의 간독성에 미치는 효과)

  • Yoon, Jung-Sik;Roh, Young-Bok
    • Applied Microscopy
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    • v.33 no.1
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    • pp.59-78
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    • 2003
  • This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The first group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the second one with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). The third one which had already been injeted with chitosanoligosaccharide (0.5% Solution) aweek before (group Ch7+Cd) was used. In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, enzyme activity in serum, glutathione peroxidase (GSHPx) activity and glutathione reductase (GR) activity were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. As the result of enzyme activity in serum, the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in chitosanoligosaccharide-injected groups Cd+Chi and Chi7+Cd was lower than in group Cd. GSH-Px activity was sharply increased in groups Cd+Chi and Chi7+Cd compared to group Cd. GR activity was conspicuously decreased in groups Cd+Chi and Chi7+Cd compared to group Cd. As the result of light microscopic observation, liver cell necrosis caused by cadmium poisoning was obseved in liver cells. The finding of group Cd+Chi and Chi7+Cd was similar total on of normal groups. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi and Chi7+Cd, mitochondria wiht high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

The Oxytocinergic Neurons in Hypothamo-hypophysial Tract Contributes to CNS Pathway Innervating Ovary in Rat (시상하부-뇌하수체로 Oxytocin신경세포의 난소로 투사하는 중추신경로에 관한 연구)

  • Byun, Kyung-Hee;Oh, Jee-Hyun;Jo, Seung-Mook;Lee, Bong-Hee
    • Applied Microscopy
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    • v.40 no.4
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    • pp.211-218
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    • 2010
  • The mammalian ovary is innervated by sympathetic and sensory neurons which contribute to regulating several aspects of ovarian function, including blood flow, steroidogenesis and follicular development. The existence of a neural connection between central neurons and the ovary has been rarely reported, but the mechanism underlying integration of ovarian activity to broader neuroendocrine responses has not been reported. We have now used a viral transneuronal tracing technique combined with a conventional retrograde labeling procedure of CT-HRP to demonstrate that oxytocin-producing neurons of the hypothalamus are synaptically connected to the ovary. Since ovarian activity is suppressed but the activity of oxytocin neurons is increased during breast feeding. Our finding that the oxytocinergic neural connection is likely to provide a direct transsynaptic mechanism by which the central nervous system maintains the state of infertility that accompanies lactation in mammals.

Inhibitory Effects of Several Korean Traditional Herbs on Anaphylactic Reaction and Mast Cell Activation (아나필락시스 반응과 비만세포 활성화에 대한 한국전통약제의 억제효과)

  • Chai, Ok-Hee
    • Applied Microscopy
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    • v.40 no.4
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    • pp.201-209
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    • 2010
  • Korean traditional herbs, especially Anemarrhena asphodeloides (A. asphodeloides), Salvia miltiorrhiza (S. miltiorrhiza), and Terminalia chebula (T. chebula) have been known to have the immunomodulatory, anti-tumor, and anti-inflammatory effects. However, direct cellular mechanism underlying the mast cell-mediated anaphylaxis-like reaction has poorly been understood. In the present study, the effects of the methanol extracts of A. asphodeloides (MEAA), S. miltiorrhiza (MESM), and T. chebula (METC) on anaphylactic reaction were investigated. Using in vitro and in vivo experiments, the influences of MEAA, MESM, and METC on the compound 48/80-induced anaphylaxis-like reaction and mast cell activation, and IgEmediated PCA were examined. Results are below; 1) MEAA, MESM, and METC significantly inhibited systemic anaphylaxis-like reaction, ear swelling response, and IgE-mediated PCA. 2) the compound 48/80-induced mast cell degranulation, histamine release of rat peritoneal mast cells (RPMC) were significantly inhibited by the pretreatment with MEAA, MESM, and METC, and 3) the compound 48/80-induced calcium influx in RPMC was significantly inhibited by the pretreatment with MEAA, MESM, and METC. These results suggest that MEAA, MESM, and METC may be an activity to inhibit the compound 48/80-induced or anti-DNP IgE-mediated anaphylactic reactions by blocking histamine release and calcium uptake into RPMC. MEAA, MESM, and METC potentially may serve as an effective therapeutic tool for allergic diseases.