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101.
Protein tyrosine phosphatase-1B (PTP-1B), a negative regulator of insulin signaling, may be an attractive therapeutic target for type 2 diabetes mellitus. High throughput screening (HTS) for PTP-1B inhibitors using compounds from the Korea Chemical Bank identified several hits (active compounds). Among them, a hit with 1,2-naphthoquinone scaffold was chosen for lead development. KR61639, [4-[1-(1H-indol-3-yl)-3,4-dioxo-3,4-dihydro-naphthalen-2-ylmethyl]-phenoxy]-acetic acid tert-butyl ester, inhibited human recombinant PTP-1B with an IC(50) value of 0.65 microM in a noncompetitive manner. KR61639 showed modest selectivity over several phosphatases and increased insulin-stimulated glycogen synthesis in HepG2 cells and stimulated 2-deoxyglucose uptake in 3T3/L1 adipocytes. In addition, in vivo study using ob/ob mouse demonstrated that KR61639 exerted a hypoglycemic action when given orally. Thus, KR61639 may be a good starting point for lead optimization in developing a novel antidiabetic agent. 相似文献
102.
Jeong TC Chang HW Lee ES Jeon TW Jeong HG Holsapple MP 《Journal of toxicology and environmental health. Part A》2004,67(23-24):1955-1970
Studies demonstrated that cocaine-induced immunosuppression is mediated by metabolites of cocaine. Although SKF 525-A inhibited cocaine N-demethylation in liver S9 fractions isolated from female B6C3F1 mice, our study showed that pretreatment of mice with SKF 525-A potentiated cocaine-induced suppression of the antibody response to sheep red blood cells. An increase in formaldehyde generation was subsequently shown following incubation of cocaine with the S9 fractions prepared from SKF 525-A-treated mice, indicating the possibility of cytochrome P-450 (CYP) induction. Therefore, the inductive effects of SKF 525-A on CYP enzyme activities and proteins were investigated in female B6C3F1 mice to elucidate the potentiation of cocaine-induced immunosuppression by SKF 525-A. When SKF 525-A was administered at 10, 20, or 40 mg/kg/d intraperitoneally for 7 consecutive days, both ethoxyresorufin O-deethylase and pentoxyresorufin O-dealkylase activities were induced dose-dependently. Furthermore, the induction of enzymatic activity was time dependent. Meanwhile, when the type of isozyme induced by SKF 525-A was analyzed by Western immunoblotting with monospecific anti-CYP 1A and anti-CYP 2B antibodies, only the CYP 2B appeared to be induced. From in vitro inhibition studies with monoclonal antibodies, it was confirmed that the induced activity of ethoxyresorufin O-deethylase by SKF 525-A was due to increased levels of CYP 2B proteins. Our present results provide an explanation for the potentiation of cocaine-induced immunosuppression by repeated exposure to SKF 525-A. Our results also indicate that ethoxyresorufin O-deethylase, a selective substrate for CYP 1A, may also be catalyzed by CYP 2B. 相似文献
103.
Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s 总被引:4,自引:0,他引:4
Lee SK Kim NH Lee J Kim DH Lee ES Choi HG Chang HW Jahng Y Jeong TC 《Planta medica》2004,70(8):753-757
Rutaecarpine is an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa. Recently, rutaecarpine has been characterized to have an anti-inflammatory activity through cyclooxygenase-2 inhibition. In the present studies, the effects of rutaecarpine on liver cytochrome P450 s (P450s) and P450 s involved in the metabolism of rutaecarpine were studied in vivo and in vitro, respectively, because the data are crucial in the early development of rutaecarpine as a new drug candidate. Oral administration to male ICR mice of rutaecarpine for 3 consecutive days induced liver P450 1A-, 2B- and 2E1-selective monooxygenase activities. The induction of P450 1A and 2B by rutaecarpine was confirmed by Western immunoblotting. When rutaecarpine was incubated with rat liver microsomes in the presence of an NADPH-generating system, five metabolites were detected by UV and mass spectral analyses. The 3-methylcholanthrene- and phenobarbital-induced microsomes greatly increased the formation of metabolites. Our present results suggest that rutaecarpine might induce P450 1A and 2B in mice, and that P450 1A and 2B might predominantly metabolize rutaecarpine in rat liver microsomes. 相似文献
104.
Bioassay-guided fractionation of the EtOAc-soluble extract of Dendrobium moniliforme afforded a new phenanthraquinone-type metabolite, 7-hydroxy-5,6-dimethoxy-1,4-phenanthrenequinone ( 1), along with the previously reported 5-hydroxy-3,7-dimethoxy-1,4-phenanthrenequinone ( 2). The structures of the compounds were identified mainly on the basis of MS and NMR data. Compound 1 inhibited VHR dual-specificity protein tyrosine phosphatase (DS-PTPase) activity in a dose-dependent manner, displaying an IC (50) value of 3.0 +/- 0.2 microM. 相似文献
105.
Laparoscopic duodenojejunostomy for management of superior mesenteric artery syndrome: two cases report and a review of the literature 总被引:2,自引:0,他引:2
Superior mesenteric artery(SMA) syndrome is rare disorder, which is caused by a reduction in the aortomesenteric angle causing a duodenal obstruction. It is usually occurs after a period of weight loss, nausea, and vomiting by a partial obstruction of the third portion of the duodenum. If conservative management fails then a laparotomy with a duodenojejunostomy is indicated. Recently, a minimally invasive or laparoscopic approach to the retroperitoneum or duodenal detachment was introduced. Although the role of a laparoscopy in managing SMA syndrome is not clearly defined, a laparoscopic duodenojejunostomy may be an alternative approach to the surgical treatment of SMA syndrome cases. Two cases of superior mesenteric artery syndrome that were treated laparoscopically after medical therapy failure are described. The 4-port procedure was performed. A dilated bowel on the third portion of the duodenum was observed below the transverse mesocolon and to right of the superior mesenteric artery. A proximal loop of the jejunum was anastomosed to the duodenum using an endoscopic GIA stapler. The surgery time and hospital length of stay were acceptable. No complications were encountered in this study. A laparoscopic duodenojejunostomy is a feasible alternative option for treating SMA syndrome. It provides the benefits of being a definitive and minimally invasive surgical technique in a duodenal obstruction. 相似文献
106.
Lee EB Shin KC Lee YJ Lee YJ Cheon GJ Jeong JM Son MW Song YW 《Nuclear medicine communications》2003,24(6):689-696
Radiation synovectomy is a useful treatment modality in patients with refractory synovitis. We have developed a 188Re-tin-colloid as a new radiopharmaceutical agent and investigated its efficacy and safety in patients with rheumatoid arthritis. Radiation synovectomy was performed using 188Re-tin-colloid in 22 knees from 21 rheumatoid arthritis patients refractory to intra-articular corticosteroid injection. The efficacy and safety of administration of 370-1110 MBq of 188Re-tin-colloid were evaluated after 1, 3, 6, 9 and 12 months. Pain intensity on a visual analogue scale decreased significantly 12 months after therapy (mean+/-SD: 68.0+/-26.1 mm vs. 25.1+/-23.4 mm; P=0.0001 by the paired t-test). Pain decreased in 19 cases (86.3%), joint tenderness improved in 14 cases (63.6%) and joint swelling was reduced in all cases (100%). 188Re-tin-colloid was safe. The residual activity of 188Re in the blood was 0.077%+/-0.25% of the injected dose. The radioactivity of 188Re in the urine was 0.14%+/-0.13% of the injected dose. Transient reactive synovitis was observed in 18 cases (81.8%). No clinical side-effects or abnormalities in leucocyte count, platelet count, liver function tests or urine analysis were observed in any patient. In conclusion, in this first study of radiation synovectomy using 188Re-tin-colloid for patients with rheumatoid arthritis, the treatment resulted in the improvement of arthritis and was well tolerated. 相似文献
107.
Jeong TC Kim JY Ji HY Lee DH Kim SO Lim H Yoo SE Lee HS 《Archives of pharmacal research》2003,26(10):800-804
The effects of KR-31378, a neuroprotective agent for ischemia-reperfusion damage, on liver microsomal cytochrome P450s (CYPs) were investigated in male Sprague Dawley rats. When rats were treated orally with KR-31378 for 7 consecutive days, CYP3A-selective erythromycin N-demethylase (ERDM) activity was significantly induced in a dose-dependent manner. In Western immunoblotting, CYP 3A proteins were clearly induced by treatment with KR-31378. Within 24 h after treatment with 80 mg/kg of KR-31378, ERDM activity was induced in liver microsomes in accompanied by induction of the level of CYP 3A proteins. The present results suggest that KR-31378 might modulate the expression of CYP 3A enzymes in humans. 相似文献
108.
Kim JY Lee SK Kim CH Jeon TW Moon CK Lee HS Yoo SD Lee ES Jeong TC 《Archives of pharmacal research》2003,26(5):394-404
Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-O-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs. 相似文献
109.
Kim JS Na CS Hwang WJ Lee BC Shin KH Pak SC 《The American journal of Chinese medicine》2003,31(3):481-488
As pregnancy advances, prostaglandins (PG) increase in the uterus, leading to elevated uterine contractility. Therefore, regulating the concentration of PG in the uterus can be a key factor for controlling the duration of labor. Since the synthesis of PGs in the uterus is catalyzed by cyclooxygenase-2 (COX-2), devising a tool to regulate the expression of COX-2 could provide a method for treating complicated labor. In this study, Sp-6 acupuncture treatment was evaluated for its potential in controlling uterine motility. Immunohistochemical methods showed the COX-2 enzyme was primarily found in the endometrium and myometrium of rat uterus. COX-2 expression in these two locations were intensified by pregnancy, but reduced by acupuncture at the Sp-6 acupoint. Uterine motility monitored during Sp-6 acupuncture was reduced by 28.15% (p < 0.05) and 19.88% (p < 0.05) in pregnant rats and non-pregnant rats, respectively. The significant reduction of uterine motility in pregnant rat suggests a role for Sp-6 acupuncture in regulating the expression of COX-2 during pregnancy. These results suggest that Sp-6 acupuncture could be used as a complementary method for controlling labor in human pregnancy. 相似文献
110.
Gangliocytoma of the spinal cord: a case report 总被引:3,自引:0,他引:3
Choi YH Kim IO Cheon JE Kim WS Yeon KM Wang KC Cho BK Chi JG 《Pediatric radiology》2001,31(5):377-380
We present a case of intramedullary spinal gangliocytoma in a 7-year-old girl who presented with scoliosis and progressive
weakness of both legs. The tumour involved the whole spinal cord and medulla oblongata and was composed of inner cystic and
outer solid components. On MRI, the solid portion of the lesion showed strong enhancement at the thoracolumbar level and mild
enhancement at the cervical and medullary levels. Histological examination of the surgical specimen showed neoplastic ganglion
cells arranged irregularly in benign normocellular glial background, which made a diagnosis of gangliocytoma.
Received: 15 November 1999 Accepted: 21 November 2000 相似文献