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Comparisons in Pharmacokinetic Profiles of New Platinum Coordination Complexes, KBP31705-C127 and KBP30603-901 with Cisplatin and Carboplatin (신규 백금착물 항암제 KBP31705-C127, KBP30603-901의 Cisplatin 및 Carboplatin과의 약동력학적 동태 비교)

  • 정인숙;이주선;허수정;김진숙;진창배;김동현;김명배;박경수;손연수
    • Biomolecules & Therapeutics
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    • v.4 no.4
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    • pp.349-353
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    • 1996
  • The present study examined pharmacokinetic profiles of KBP31705-Cl27 and KBP30603-901, new platinum coordination complexes synthesized as anticancer candidates, in comparison with two well-known platinum-containing anticancer agents, cisplatin and carboplatin in rats. Under sodium pentobarbital anesthesia of male Sprague-Dawley rats, urinary bladder, and femoral artery and vein were catheterized for urine collection, blood sampling and drug injection, respectively Following i.v. administration of cisplatin (2 mg/kg), KBP31705-C127 (2 mg/kg), carboplatin (20 mg/kg) or KBP30603-901 (20 mg/kg), blood samples were collected at 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 and 120 minutes. Urine samples were collected at 1-hr interval for 4 hr. Platinum concentrations in plasma and urine were measured using an inductively coupled plasmamass spectrometer. The plasma concentration-time curves were biphasic for all drugs during the time period studied. Compared with cisplatin, KBP31705-C127 showed similar decay patters in the alpha- and betaphases with slightly lower plasma concentrations. Urinary platinum excretion for cisplatin and KBP31705-C 127 was 56 and 52% of the administered dose in 4 hr, respectively. With regard to carboplatin and KBP 30603-901, a similar decay pattern was also observed in the alpha-phase. The half life of KBP30603-901 in the beta-phase, however, was much longer than that of carboplatin, which was consistent with the urinary excretion results that 46 and 59% of the administered dose were excreted in the urine in 4hr, respectively. The results suggest that platinum coordination complexes are primarily excreted via the renal route and KBP30603-901 can elicit longer duration of action due to slower renal excretion compared to carboplatin.

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Glucose Transporters and AMP-Activated Protein Kinase Modulation Effects of Decursin and Decursinol Angelate on Diabetic Rats (당뇨유발 흰쥐에서 당수송 인자와 AMP-Activated Protein Kinase의 조절에 대한 데커신과 데커시놀 안젤레이트의 효과)

  • Ok, Seon;Lee, Ju-Hee;Kim, Ik-Hwan;Kang, Jae-Seon
    • YAKHAK HOEJI
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    • v.55 no.4
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    • pp.301-308
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    • 2011
  • Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

The Effect of Lipo-PGE1 According to the Routes of Administration on the Survival of Transverse Rectus Abdominis Musculocutaneous Flap in Rats (Lipo-PGE1의 투여경로가 흰쥐의 횡복직근피판의 생존률에 미치는 효과)

  • Kim, Sung-Sik;Byeon, Jun-Hee;Yoo, Gyeol;Han, Ki-Taik
    • Archives of Plastic Surgery
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    • v.32 no.1
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    • pp.12-18
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    • 2005
  • The Transverse rectus abdominis musculocutaneous (TRAM) flap has been commonly used for autologous breast reconstruction. Despite these clinical usefulness, the TRAM flap is prone to partial flap or fat necrosis in especially pedicled flap. To improve flap survival, the surgical delay procedures and pharmacological treatments have been developed. In many studies for the pharmacological treatment, Lipo-$PGE_1$ has demonstrated a marked ability to improve flap survival and it's effect has been proved similar to surgical delay procedure. The purpose of this study is to determine the most effective route of Lipo-$PGE_1$ administration as a pharmacological treatment in TRAM flap of the rat. Fifty male Sprague-Dawley rats weighing 300-350 gm were divided into five groups, One week before flap elevation, Lipo-$PGE_1$($2{\mu}g/kg$) was injected three times in a week and than the left inferior epigastric vessel based TRAM flap ($5.0{\times}3.0cm$) elevated; group I: no procedure before flap elevation; group II: intraperitoneal injection; group III: intravenous injection; group IV: subcutaneous injection; group V: topical application. A flap was assessed at postoperative 7 days by comparison of flap survival rate, vessel counts(H-E stain), and vascular endothelial growth factor(VEGF) protein expressed by Western blot. The results demonstrated that the mean percentages of the flap survival area in group III were significantly higher than that of any other group(p<0.05). The vessel counts of all experimental groups were statistically higher than that of control group(p<0.05). Only in group III, the VEGF protein expression was increased significantly than control group and there are no difference in other experimental groups. In conclusion, the intravenous administration of the Lipo-$PGE_1$ is the most effective on flap survival, and the VEGF induced by Lipo-$PGE_1$ has some positive effects on new vessel formation and flap survival.

Pharmacokinetic Study of CKD-602, A New Camptothecin Derivative: Distribution, Metabolism and Excretion (신규 캄토테신계 항암제 CKD-602의 약물동태: 분포, 대사 및 배설)

  • Lee, Ju-Mong;Lee, Jun-Hee;Kim, Joon-Kyum;Shin, Hee-Jong;Lee, Hyung-Ki;Lee, Sang-Joon;Hong, Chung-Il
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.437-446
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    • 1998
  • The distribution, metabolism and excretion of CKD-602{20(S)-7-[2-(N-Isopropylamino)ethyl]camptothecin HCI), a new camptothecin derivative, were investigated in rats after a sing le administration of CKD-602. 1. The tissue levels of CKD-602 given to mice by the intravenous route at a dose of 20mg/kg were the highest in intestine, followed in descending order by kidney, liver, stomach,lung, heart, spleen and plasma. The concentrations of CKD-602 after 24hrs decreased to less than 2% of the peak level in most tissues except the skin. The urinary and fecal excretion of CKD-602 were 47.6% and 44.4% of the administered dose, respectively, with 0.7% remaining in the rinse. 2. After administration of CKD-602 at 10mg/kg in rats, metabolism of this compound was examined in plasma, urine, and feces. The plasma samples were collected for 24hr, urinary and fecal samples for 72hr. While any peak of CKD-602 in HPLC chromatograms was not detected from plasma and urine it was detected in feces (peaks, 9.8 min). However, additional peak area was about 0.5% of the peak area of parent CKD-602. Therefore, CKD-602 may be eliminated with the parent form and rarely metabolized in the body. 4. After I.v. administration of CKD-602 at 10mg/kg in rats, urinary and fecal excretions were examined for 72hrs post dose period. 87% of total urinary excretion of CKD-602 was excreted within 8hr after administration, 53%, and 32% of total fecal excreted amounts were determined in 0-24 hr and 24-48hr periods, respectively. The total excretion amounts of CKD-602 into urine and feces were 94% of the administered dose.

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3D Porous Foam-based Triboelectric Nanogenerators for Energy Harvesting (3차원 기공구조를 이용한 정전기반 에너지 하베스팅 나노발전기 소자제조)

  • Jeon, Sangheon;Jeong, Jeonghwa;Hong, Suck Won
    • Journal of the Microelectronics and Packaging Society
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    • v.26 no.1
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    • pp.9-15
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    • 2019
  • Here, we present a facile route to fabricate a vertically stacked 3D porous structure-based triboelectric nanogenerator (TENG) that can be used to harvest energy from the friction in a repetitive contact-separation mode. The unit component of TENG consists of thin Al foil electrodes integrated with microstructured 3D foams such as Ni, Cu, and polyurethane (PU), which provide advantageous tribo-surfaces specifically to increase the friction area to the elastomeric counter contact surfaces (i.e., polydimethylsiloxane, PDMS). The periodic contact/separation-induced triboelectric power generation from a single unit of the 3D porous structure-based TENG was up to $0.74mW/m^2$ under a mild condition. To demonstrate the potential applications of our approach, we applied our TENGs to small-scale devices, operating 48 LEDs and capacitors. We envision that this energy harvesting technology can be expanded to the applications of sustainably operating portable electronic devices in a simple and cost-effective manner by effectively harvesting wasted energy resources from the environment.