• Title/Summary/Keyword: Drug-associated

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Inhibitory Effects of Triticum aestivum L. Extracts on Liver Lipid Accumulation in High Fat-Fed Mice (고지방식이 섭취 마우스의 간 조직의 지질 축적에 대한 밀순 추출물의 억제 효과)

  • Lee, Sun-Hee;Lim, Sung-Won;Lee, Young-Mi;Seo, Joo-Won;Kim, Dae-Ki
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.309-316
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    • 2011
  • Fatty liver disease refers to a range of disorders associated with fatty liver, which occur in excessive eating, evident infection or significant consumption of alcohol. This study was to investigate the effects of water and ethanol extracts of Triticum aestivum young leaf on lipid metabolism and accumulation in liver of mice fed with high-fat diet. Male C57BL/6 mice were divided into normal diet group, high fat diet (HFD) group, high fat diet group administrated with 200 mg/kg/day of T. aestivum water extract (HFD-TAWE) and high-fat group administrated with 200 mg/kg/day of T. aestivum ethanol extract (HFD-TAEE). TAWE and TAEE were administrated orally for 5 weeks once at the same time point. Both TAWE and TAEE significantly reduced body weight, food intake and liver tissue weight, which were augmented in high fat-fed mice. The serum levels of triglyceride, total and LDL-cholesterol also were significantly attenuated in both HFD-TAWE and HFD-TAEE groups compared to the HFD group. Moreover, administration of HFD-TAWE or HFD-TAEE reduced the lipid accumulation in liver tissue of mice fed with high fat diet. Levels of total lipids and triglyceride in liver tissues also was significantly reduced in HFDTAWE and HFD-TAEE groups compared to HFD group. The activities of serum ALT and AST revealed in HFD group were remarkedly decreased in HFD-TAEE groups. These results indicate that both water and ethanol extract of T. aestivum may improve the lipid accumulation in liver as well as lipid metabolism in serum, and that in particular, the ethanol extract of T. aestivum may has the potent anti-hyperlipidemic effect, suggesting that it may be a useful candidate for the therapy preventing fatty liver diseases.

Catalpol and Mannitol, Two Components of Rehmannia glutinosa, Exhibit Anticonvulsant Effects Probably via GABAA Receptor Regulation

  • Kim, Mikyung;Acharya, Srijan;Botanas, Chrislean Jun;Custodio, Raly James;Lee, Hyun Jun;Sayson, Leandro Val;Abiero, Arvie;Lee, Yong Soo;Cheong, Jae Hoon;Kim, Kyeong-man;Kim, Hee Jin
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.137-144
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    • 2020
  • Epilepsy is a brain disorder that affects millions of people worldwide and is usually managed using currently available antiepileptic drugs, which result in adverse effects and are ineffective in approximately 20-25% of patients. Thus, there is growing interest in the development of new antiepileptic drugs with fewer side effects. In a previous study, we showed that a Rehmannia glutinosa (RG) water extract has protective effects against electroshock- and pentylenetetrazol (PTZ)-induced seizures, with fewer side effects. In this study, the objective was to identify the RG components that are responsible for its anticonvulsant effects. Initially, a number of RG components (aucubin, acteoside, catalpol, and mannitol) were screened, and the anticonvulsant effects of different doses of catalpol, mannitol, and their combination on electroshock- and chemically (PTZ or strychnine)-induced seizures in mice, were further assessed. Gamma-aminobutyric acid (GABA) receptor binding assay and electroencephalography (EEG) analysis were conducted to identify the potential underlying drug mechanism. Additionally, treated mice were tested using open-field and rotarod tests. Catalpol, mannitol, and their combination increased threshold against electroshock-induced seizures, and decreased the percentage of seizure responses induced by PTZ, a GABA antagonist. GABA receptor binding assay results revealed that catalpol and mannitol are associated with GABA receptor activity, and EEG analysis provided evidence that catalpol and mannitol have anticonvulsant effects against PTZ-induced seizures. In summary, our results indicate that catalpol and mannitol have anticonvulsant properties, and may mediate the protective effects of RG against seizures.

Establishment of an Allo-Transplantable Hamster Cholangiocarcinoma Cell Line and Its Application for In Vivo Screening of Anti-cancer Drugs

  • Puthdee, Nattapong;Vaeteewoottacharn, Kulthida;Seubwai, Wunchana;Wonkchalee, Orasa;Keawkong, Worasak;Juasook, Amornrat;Pinloar, Somchai;Pairojkul, Chawalit;Wongkham, Chaisiri;Okada, Seiji;Boonmars, Thidarut;Wongkham, Sopit
    • Parasites, Hosts and Diseases
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    • v.51 no.6
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    • pp.711-717
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    • 2013
  • Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.

Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results

  • Aghili, Mahdi;Sotoudeh, Sarvazad;Ghalehtaki, Reza;Babaei, Mohammad;Farazmand, Borna;Fazeli, Mohammad-Sadegh;Keshvari, Amir;Haddad, Peiman;Farhan, Farshid
    • Radiation Oncology Journal
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    • v.36 no.1
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    • pp.17-24
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    • 2018
  • Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

Clinical Analysis of Surgical Results and Preoperative Management of Acute Aortic Dissection (급성 대동맥박리증의 수술성적 및 수술전 처치에 대한 임상적 고찰)

  • 현성열;박국양;이재웅;이창하;전양빈;박철현;염석란;신종환;민순식
    • Journal of Chest Surgery
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    • v.35 no.12
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    • pp.876-881
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    • 2002
  • Acute aortic dissection associated with high mortality rate has an extremely poor prognosis if early diagnosis and treatment are not received. Recently, with advanced computed tomography and echocardiography, diagnostic rate is higher and early operation is possible. Therefore preoperative medical therapy at ER(emergency room) lowered the mortality rate. This study was done to analyze the results with preoperative management at ER and operations, retrospectively. Material and Method: A series of 42 patients treated surgically for acute aortic dissections from 1991 to 2001 were included in this study. There were 18 males and 24 females. Mean age was 51.1 years. The admission course through emergency and outpatient department(OPD) was 34 and 8 respectively. Result: 26 patients underwent ascending aorta replacement-7 combined aortic valve replacements, 7 patients underwent descending aorta replacements and 9 patients received Bentall's operation. At emergency department, 20 patients received antihypertensive drugs and $\beta$-receptor blockers and 6 patients died. 22 patients did not receive antihypertensive and $\beta$-receptor block drugs and 10 patients died. There were 16(38%) overall deaths. Conclusion: Early diagnosis at ER or OPD is essential for acute aortic dissection, and it is important to select the most appropriate noninvasive interventions as possible. Therefore, preoperative drug therapy at ER is suggested according the patient conditions.

Risk factors and clinical characteristics of necrotizing enterocolitis in full-term newborns (만삭아에서의 괴사성 장염의 위험인자와 임상증상)

  • Jeoung, Young Mi;Je, Hyun Gon;Son, Sang Hee
    • Clinical and Experimental Pediatrics
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    • v.49 no.5
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    • pp.489-493
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    • 2006
  • Purpose : The purpose of this study was to determine those factors which could contribute to the development of necrotizing enterocolitis(NEC) in fullterm. Methods : We retrospectively reviewed the medical record of 20 full-terms with NEC(${\geq}$modified Bell's staging criteria IIa) who were admitted to the Neonatal Intensive Care Unit of Il Sin Christian hospital from January 1998 through July 2005, and for each case, the next 2 healthy newborns were matched as controls. Results : Mean gestational age and birth weight in the fullterm with NEC group was 38.42 weeks and 2,915 g; in the healthy fullterm without NEC group, it was 38.61 weeks and 3,148 g. When compared with the control group, NEC infants had a significantly higher frequency of chorioamnionitis, protracted diarrhea. As for Apgar score at 1 min <7, respiratory problem, congenital heart disease. there were no differences in frequency of preeclampsia, maternal diabetes, maternal drug abuse, meconium-stained amniotic fluid, polycythemia or exchange transfusion. Conclusion : Most of these full term infants have a predisposing factor before developing NEC. Our study suggested that NEC in fullterm infants was significantly associated with protracted diarrhea, and congenital heart disease.

A multi-institutional analysis of sternoclavicular joint coverage following osteomyelitis

  • Othman, Sammy;Elfanagely, Omar;Azoury, Said C.;Kozak, Geoffrey M.;Cunning, Jessica;Rios-Diaz, Arturo J.;Palvannan, Prashanth;Greaney, Patrick;Jenkins, Matthew P.;Jarrar, Doraid;Kovach, Stephen J.;Fischer, John P.
    • Archives of Plastic Surgery
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    • v.47 no.5
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    • pp.460-466
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    • 2020
  • Background Sternoclavicular joint (SCJ) osteomyelitis is a rare pathology requiring urgent intervention. Several operative approaches have been described with conflicting reports. Here, we present a multi-institutional study utilizing multiple surgical pathways for SCJ reconstruction. Methods A multi-institutional retrospective cohort study was conducted to identify patients who underwent surgical repair for sternoclavicular osteomyelitis between 2008 and 2019. Patients were stratified according to reconstruction approach: single-stage reconstruction with advancement flap and delayed-reconstruction with flap following initial debridement. Demographics, operative approach, type of reconstruction, and postoperative outcomes were analyzed. Results Thirty-two patients were identified. Mean patient age was 56.2±13.8 years and 68.8% were male. The average body mass index (BMI) was 30.0±8.8 kg/㎡. The most common infection etiologies were intravenous drug use and bacteremia (both 25%). Fourteen patients (43.8%) underwent one-stage reconstruction and 18 (56.2%) underwent delayed two-staged reconstruction. Both single and delayed-stage groups had comparable rates of reinfection (7.1% vs. 11.1%, respectively), surgical site complications (21.4% vs. 27.8%), readmissions (7.1% vs. 16.6%), and reoperations (7.1% vs. 5.6%; all P>0.05). The single-stage reconstruction group had a significantly lower BMI (26.2±5.7 kg/㎡ vs. 32.9±9.1 kg/㎡; P<0.05) and trended towards shorter hospital length of stay (11.3 days vs. 17.9 days; P=0.01). Conclusions Both single and delayed-stage approaches are appropriate methods with comparable outcomes for reconstruction for SCJ osteomyelitis. When clinically indicated, a single-stage reconstruction approach may be preferable in order to avoid a second operation as associated with the delayed phase, and possibly shortening total hospital length of stay.

No Association of $CYP2D6^*4$ and $CYP2D6^*10$ Polymorphisms with Tardive Dyskinesia in Korean Schizophrenics (한국인 정신분열병 환자의 지연성 운동장애와 $CYP2D6^*4$$CYP2D6^*10$ 다형성들의 연합에 대한 고찰)

  • Woo, Sung-Il;Kang, Dong-Woo;Seo, Han-Gil;Kim, Bong-Jo;Lee, In-Sang;Jeong, Geun-Hoa;Park, So-Young;Jung, Chi-Yeong;Lee, Hwan-Cheol;Jeong, Kyeong-Cheon;Sohn, Jin-Wook
    • Korean Journal of Biological Psychiatry
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    • v.7 no.2
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    • pp.140-146
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    • 2000
  • P450 CYP2D6 enzyme(=debrisoquine hydroxylase) is known to metabolize many neuroleptics and some genetic polymorphisms in the CYP2D6 gene were reported to be associated with tardive dyskinesia(TD). We investigeted the association of two genetic polymorphisms in the CYP2D6 gene, $CYP2D6^*4$ and $CYP2D6^*10$, with TD in Korean schizophrenic subjects. Subjects consisted of 71 Korean schizophrenics and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). There were no statistically significant differences in the demographic variables of age, male to female percentage and the current antipsychotic(CPZ equivalent) dose between the group with TD and the group without TD. But the duration of antipsychotic drug exposure was significantly higher in the group without TD(p=0.000, by independent t-test). The mean AIMS score in the group with TD was $11.2{\pm}6.6$(S.D.). Genotypings for the presence of $CYP2D6^*4$ and $CYP2D6^*10$ were done using PCR amplifications and endonuclease digestions. There were no statistically significant genotypic and alleleic associations between TD and $CYP2D6^*4$(by chisquare tests), and between TD and $CYP2D6^*10$(by chi-square tests). These results indicate that the $CYP2D6^*4$ and $CYP2D6^*10$ polymorphisms have no significant roles in the causation of TD.

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Effect of Areca Nut on Helicobacter pylori-Induced Gastric Diseases in Mice

  • Lee, Jinwook;Gunawardhana, Niluka D.;Jang, Sungil;Choi, Yun Hui;Illeperuma, Rasika P.;Kim, Aeryun;Su, Hanfu;Hong, Youngmin A.;Kim, Ji-Hye;Kim, Jinmoon;Jung, Da-Woon;Cha, In-Ho;Bak, Eun-Jung;Cha, Jeong-Heon
    • Journal of Microbiology and Biotechnology
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    • v.26 no.10
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    • pp.1817-1823
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    • 2016
  • Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It is strongly associated with the occurrence of oral, pharyngeal, and esophageal cancer as well as systemic inflammation. However, the association between AN intake and the development of gastric lesions has not yet been identified. The aim of this study was to investigate the effect of AN on gastric diseases using a mouse model for Helicobacter pylori infection. We studied four groups of mice: those fed a normal diet (ND), those fed a diet containing 2.5% AN (AD), those fed ND and infected with H. pylori PMSS1 strain (ND/HP), and those fed AD and infected with H. pylori PMSS1 strain (AD/HP). Food intake and body weight were monitored weekly during the experiments. At 10 weeks, the mice were sacrificed, and the stomach weight, H. pylori colonization, and gastric inflammation were evaluated. The stomach weight had increased significantly in the ND/HP and AD/HP groups along with increases in H. pylori colonization; however, there was no significant difference between these two groups with respect to stomach weight and colonization. On histological grading, mononuclear cell infiltration was severer in the AD/HP group than in the ND/HP group. These data suggest that chronic gastric inflammation was aggravated by AN treatment in the mice with H. pylori-induced gastric lesions. Furthermore, as previously suggested, this animal model is useful to determine the effect of potential carcinogens on gastric lesions induced by H. pylori infection.

The Relationship between Antiviral Drugs for Chronic Hepatitis B and Diagnostic Markers

  • Jeong, Da Un;Hyun, Sung Hee;Kim, In Sik
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.2
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    • pp.57-67
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    • 2011
  • In this study, we investigated the correlation between the administration of various antiviral agents and the alternation of specific biomarkers induced by the hepatitis B virus (HBV). Eligible subjects diagnosed with chronic hepatitis B were prescribed with antiviral drugs at the Gastroenterology Internal Medicine Department of E University Hospital in Daejeon between May 2004 and September 2009. Lamivudine was prescribed to 66 out of 100 patients. Of the 12 patients, 6 (50.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 39 patients, 23 (59.0%) showed higher than 40 IU/L alanine aminotransferase (ALT). Of the 65 patients, 41 (63.1%) showed HBV DNA decrease of 1 log, and were prescribed with Lamivudine. Adefovir was prescribed to 3 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative, and was prescribed with Adefovir. Entecavir was prescribed to 19 (19.0%) out of 100 patients. Of the 12 patients, 3 (25.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 12 patients, 3 (125.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 14 (21.5%) showed HBV DNA decrease of 1 log, and were prescribed with Entecavir. Clavudine was prescribed to 7 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from positive HBe antigen to negative HBe antigen. Of the 39 patients, 5 (12.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 6 (9.2%) showed HBV decrease of 1 log, and were prescribed with Clavudine. These results do not show a statistically significant correlation between drugs and biomarkers. Data on combination therapy using Lamivudine and Adefovir show no statistically significant difference between drugs and biomarkers. Medications for periodic inspection was not correlated to HBe-antigen-negative conversion, ALT, and HBV DNA. HBV DNA was significantly reduced in patients with high levels of AST(aspartic acid aminotransferase) and ALT before treatment. In addition, the decrease of HBV DNA after 12 months of treatment was less frequently observed in patients treated with Lamivudine compared with other drugs. This result is associated with Lamivudine resistance. Although the association of drugs with diagnostic markers and the correct choice of treatment is difficult to determine, these results may be useful for further research on diagnosis and treatment of the hepatitis B virus.

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