• Title/Summary/Keyword: Drug-associated

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Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

  • Jo, Si-Kyoung;Hong, Ji-Young;Park, Hyen Joo;Lee, Sang Kook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.513-519
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    • 2012
  • Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

A Study on Moral Judgement and Ethical Values of Nursing students (간호학생의 도덕판단과 윤리적 가치관)

  • Kwon, Young-Mi
    • The Journal of Korean Academic Society of Nursing Education
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    • v.8 no.1
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    • pp.17-28
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    • 2002
  • The purpose of this study was to provide the basic sources for educational program that identifies moral judgement and ethical values of nursing students. The subjects consisted of 114 nursing students in college. Data were collected by the Korean Form of Moral Development Inventory(Shin, 1997) and Nursing Ethical Values(Lee, 1990) from March 5 to 21. 2002. The findings were as follows: 1. The mean score of the stage 5B was higher than the score of other stages. The mean score of P(%) was 39.15. No significant difference were found between P(%) and general characteristics. 2. The mean score of the nursing ethical values was 3.38. The nursing students took the position of deontology slightly. In nurse-colleague relationship area(4.22), the subjects should to taking evidently deontological position. 3. According to general characteristics, no significant difference was found except nurse-patient relationship area among subcategory of ethical values. The mean score of this area by influence person of moral development were significantly different at the .05 level. 4. The trend of subjects in action choices on 4 dilemmas of the DIT showed between-subjects variability. Action choices on 'Heinz and the drug', 'Doctor's dilemma', and 'webster' were 'pro' in most of subjects, whereas 'escaped prisoner' was 'con'. 5. The ethical values in human-life area associated with action choices on 'Heinz and the drug' was significantly different . And the nursing ethical values, human-life area, and nurse-nursing task relationship area were significantly different according to action choices on 'Doctor's dilemma'. 6. There was found little correlation between action choices on 4 dilemmas of the DIT and moral judgement. Also little correlation was shown between action choices on 4 dilemmas of the DIT and ethical values. No significant correlation were found between moral judgement and nurse ethical values.

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All-trans Retinoic Acid-Associated Low Molecular Weight Water-Soluble Chitosan N anoparticles Based on Ion Complex

  • Kim Dong-Gon;Choi Changyong;Jeong Young-Il;Jang Mi-Kyeong;Nah Jae-Woon;Kang Seong-Koo;Bang Moon-Soo
    • Macromolecular Research
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    • v.14 no.1
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    • pp.66-72
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    • 2006
  • The purpose of this study is to develop novel nanoparticles based on polyion complex formation between low molecular weight water-soluble chitosan (LMWSC) and all-trans retinoic acid (atRA). LMWSC nanoparticles encapsulating atRA based on polyion complex were prepared by mixing of atRA into LMWSC aqueous solution using ultrasonication. In FTIR spectra, the carbonyl group of atRA at 1690 $cm^{-1}$ disappeared or decreased when ion complexes were formed between LMWSC and atRA. In ${1}^H$ NMR spectra, specific peaks of atRA disappeared when atRA-encapsulated LMWSC (RAC) nanoparticles were reconstituted into $D_{2}O$ while specific peaks both of atRA and LMWSC appeared in $D_{2}O$/DMSO (1/3, v/v) mixture. XRD patterns also showed that the crystal peaks of atRA were disappeared by encapsulation into LMWSC nanoparticles. LMWSC nanoparticles encapsulating atRA have spherical shapes with particle size below 200 nm. The mechanism of encapsulation of atRA into LMWSC nanoparticles was thought to be an ion complex formation between LMWSC and atRA. LMWSC nanoparticles showed high atRA loading efficiency over 90$\%$ (w/w). AtRA was continuously released from nanoparticles over 10 days. In in vitro cell cytotoxicity test, free atRA showed higher cytotoxic effect against CT 26 colon carcinoma cell line on 1 day. However, RAC nanoparticles showed similar cytotoxicity against CT 26 cells on 2 day. These results suggest the potential for the introduction of LMWSC nanoparticles into various biomedical fields such as drug delivery.

Epilepsy in Korean patients with Angelman syndrome

  • Park, Sung-Hee;Yoon, Jung-Rim;Kim, Heung-Dong;Lee, Joon-Soo;Lee, Young-Mock;Kang, Hoon-Chul
    • Clinical and Experimental Pediatrics
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    • v.55 no.5
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    • pp.171-176
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    • 2012
  • Purpose: The aim of this study was to investigate the natural history of epilepsy and response to anti-epileptic drug treatment in patients with Angelman syndrome (AS) in Korea. Methods: We retrospectively reviewed the clinical records of 14 patients diagnosed with epilepsy out of a total of 17 patients with a genetic diagnosis of AS. These patients were seen at the Department of Pediatric Neurology at Severance Children's Hospital from March 2005 to March 2011. Results: Fourteen (9 males and 5 females) subjects (82.3%) were diagnosed with epilepsy in AS. The most common seizure types were generalized tonic-clonic (n=9, 27%) and myoclonic (n=9, 27%), followed by atonic (n=8, 24%), atypical absence (n=4, 12%) and complex partial seizure (n=3, 9%). The most commonly prescribed antiepileptic drug (AED) was valproic acid (VPA, n=12, 86%), followed by lamotrigine (LTG, n=9, 64%), and topiramate (n=8, 57%). According to questionnaires that determined whether each AED was efficacious or not, VPA had the highest response rate and LTG was associated with the highest rate of seizure exacerbation. Complete control of seizures was achieved in 6 patients. Partial control was achieved in 7 patients, while one patient was not controlled. Conclusion: Epilepsy is observed in the great majority of AS patients. It may have early onset and is often refractory to treatment. There are few reports about epilepsy in AS in Korea. This study will be helpful in understanding epilepsy in AS in Korea.

Biological Activity and Inhibition of Non-Enzymatic Glycation by Methanolic Extract of Rosa davurica Pall. Roots

  • Hu, Weicheng;Han, Woong;Jiang, Yunyao;Wang, Myeong-Hyeon;Lee, Young-Mee
    • Preventive Nutrition and Food Science
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    • v.16 no.3
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    • pp.242-247
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    • 2011
  • The methanolic extract of Rosa davurica Pall. roots exhibited strong antioxidant activity in a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay and was found to be a dose-dependent inhibitor of non-enzymatic formation of advanced glycation end products (AGEs), which are relevant to diabetes complications. HPLC-diode array detector (DAD) analysis of the R. davurica Pall. root extract led to the identification of four compounds: hydrocaffeic acid, catechin, epicatechin, and ellagic acid. Catechin was present in the largest amount and exhibited high antiglycation activity. A CYP3A4 assay was used to investigate potential interactions between drugs and the extract, and results suggest that the R. davurica Pall. root extract had moderate potential for interfering with drug metabolism. The R. davurica Pall. extract did not display anti-inflammatory activity on the level of that for tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in a lipopolysaccharide (LPS)-stimulated macrophage assay; however, the extract did exhibit low to moderate immunostimulatory activity in a pro-inflammatory macrophage assay. Therefore, we conclude that R. davurica Pall. root is a promising anti-AGE agent with low to moderate risks of associated inflammation or drug interaction.

Quinetides: diverse posttranslational modified peptides of ribonuclease-like storage protein from Panax quinquefolius as markers for differentiating ginseng species

  • Zhao, Qiang;Bai, Yunpeng;Liu, Dan;Zhao, Nan;Gao, Huiyuan;Zhang, Xiaozhe
    • Journal of Ginseng Research
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    • v.44 no.5
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    • pp.680-689
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    • 2020
  • Background: Peptides have diverse and important physiological roles in plants and are ideal markers for species identification. It is unclear whether there are specific peptides in Panax quinquefolius L. (PQ). The aims of this study were to identify Quinetides, a series of diverse posttranslational modified native peptides of the ribonuclease-like storage protein (ginseng major protein), from PQ to explore novel peptide markers and develop a new method to distinguish PQ from Panax ginseng. Methods: We used different fragmentation modes in the LTQ Orbitrap analysis to identify the enriched Quinetide targets of PQ, and we discovered Quinetide markers of PQ and P. ginseng using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. These "peptide markers" were validated by simultaneously monitoring Rf and F11 as standard ginsenosides. Results: We discovered 100 Quinetides of PQ with various post-translational modifications (PTMs), including a series of glycopeptides, all of which originated from the protein ginseng major protein. We effectively distinguished PQ from P. ginseng using new "peptide markers." Four unique peptides (Quinetides TP6 and TP7 as markers of PQ and Quinetides TP8 and TP9 as markers of P. ginseng) and their associated glycosylation products were discovered in PQ and P. ginseng. Conclusion: We provide specific information on PQ peptides and propose the clinical application of peptide markers to distinguish PQ from P. ginseng.

Retrospective Review of Effectiveness of Various Pharmacological Agents in Treating Burning Mouth Syndrome

  • Im, Yeong-Gwan;Kim, Byung-Gook;Kim, Jae-Hyung
    • Journal of Oral Medicine and Pain
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    • v.41 no.1
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    • pp.21-25
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    • 2016
  • Purpose: Burning mouth syndrome (BMS) is a chronic pain condition involving the oral and perioral regions, often characterized by a burning sensation and pain in elderly patients. In this study, we investigated the effectiveness of pharmacological agents for the treatment of BMS patients through a retrospective chart review. Methods: We enrolled 61 BMS subjects (57 females, 4 males; $66.4{\pm}10.9$ years of age) from among consecutive patients treated pharmacologically from January 2014 to June 2015 at Chonnam National University Dental Hospital. Patients with secondary BMS associated with local factors were excluded. The treatment period, number of pharmacological agents tried, and effectiveness of the drugs administered to each subject were analyzed. Results: The mean treatment period for the management of BMS was 2.5 months. More than three agents were tried to control BMS symptoms in 17 subjects (27.9%); two agents were used in 10 subjects (16.4%), and a single agent in 24 subjects (39.3%). Clonazepam was prescribed most frequently and was effective at relieving symptoms in 30 of 39 subjects (76.9%). Paroxetine was moderately effective, relieving symptoms in 7 of 17 subjects (41.2%). Some of the subjects benefited from tricyclic antidepressants, gabapentin, and lipoic acid. A topical local anesthetic used to supplement other systemic agents had ameliorating effects in four of six subjects. Conclusions: Within the study limitations, clonazepam was the most effective drug and antidepressants were efficacious in some subjects for relieving the symptoms of BMS. These pharmacological agents could be considered as first-line drugs for the management of BMS.

A Case of Drug Induced Interstitial Pneumonitis by Gemcitabine (Gemcitabine에 의한 약물 유발성 간질성 폐렴 1예)

  • Lee, Sung Soon;Ham, Cho Rom;Chin, Jae-Yong;Lee, Hye Ran;Kim, Su Young;Kim, Mi-young;Lee, Hyun-Kyung;Lee, Hyuk Pyo;Yum, Ho-Kee;Choi, Soo Jeon
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.315-320
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    • 2004
  • Gemcitabine is an effective newly developed chemotherapeutic agent, which is increasingly being used to treat non-small cell lung, ovarian and breast cancers. Pulmonary toxicity is usually self-limiting mild dyspnea, bronchospasm, but severe pulmonary toxicity is rarely reported. Herein, we report drug induced interstitial lung disease associated with gemcitabine treatment. High resolution computerized tomogram (HRCT) showed an increased ground glass opacity and thickened septal lines. The patient showed a rapid good response with prednisolone treatment.

Biomarkers for Combat-Related Stress and Fatigue-Mitigating Drugs Discovery (전투 스트레스 및 피로 완화 약물 탐색을 위한 생체지표)

  • Koo, Hyojin;Kim, Chang Yul;Kim, Yeonkyung;Sin, So Jung;Cheon, Kicheol;Kim, Dongsoo
    • Journal of the Korea Institute of Military Science and Technology
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    • v.21 no.2
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    • pp.246-254
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    • 2018
  • Psychological stress and physical fatigue, such as anxiety, fear, sleep disturbance, etc., caused by exposure to the war, can lead to post-traumatic stress syndrome(PTSD) or war syndrome. The military has also prepared for drug use to minimize war syndrome and preserve combat strength. However, efforts to prevent war syndrome are still lacking. This study was conducted to identify biomarkers that can track psychophysiological changes. Psychophysiological changes associated with PTSD can be divided into four main categories. The four categories are behavioral changes, changes in brain cognition, neuroimmunological changes, and changes in innate immunity. This study suggest that biomarker profile can be made by the distance moved and the anxiety-like behavior in the open field for behavior category, brain BDNF levels in the brain cognition category, serum corticosterone in the neuroimmunology category, and inflammatory cytokine levels in the innate immunity category.

In Vitro Susceptibility of Diarrhea-Causing Escherichia coli to 9 Antibacterial Agents in Clinical Use (최근 분리된 장내 병원성 대장균의 항균제 감수성)

  • Kim, Jai-Ho;Kim, Kyung-Hee;Cho, Yaug-Ja;Suh, Inn-Soo
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.155-162
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    • 1987
  • To determine the prevalence of antibiotic resistance in fecal E. coli and to investigate possible associations between antibiotic resistance and other plasmid-mediated virulence properties, antibiotic disk susceptibility tests for nine antibiotics were done on 141 strains of E. coli isolated from diarrheal children and well controls. Eighty two percent of the test strains were resistant to one or more antibiotics. Antibiotics to which the test strains were most resistant in descending order were ampicillin (85%), trimethoprim/sulfamethoxazol (60%), and cephalothin (55%). Seventy nine percent of these resistant strains were resistant to two or more antibiotics. All 141 test strains were sorted into enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroadherent E. coli (EAEC) and non-pathogenic E. coli and the percentages of strains resistant to multiple antibiotics were compared. Among ETEC regardless of its source, multiple drug resistance was more frequent in strains producing heatstable enterotoxin (ST) only than in strains producing only heat-labile enterotoxin (LT) or both. In EAEC, multiple resistance was more frequently associated with strains isolated from diarrheal patients than with those from well controls. The major antibiotic resistance patterns possessed by multiple resistant enteropathogenic strains were $SXT^R$ $AM^R$, $CR^R$, and $SXT^R$ $AM^R$ $CR^R$. Of 28 ST- producing $SXT^R$ ETEC, 26(96%) were also resistant to ampicillin and 17 (61%) were resistant to cephalothin. The similar pattern was observed in EAEC and EPEC as well. This study has important implications for the treatment of E. coli diarrhea with antibiotics because it is possible that dissemination of virulence could occur under the force of selective antibiotic pressure. In addition, this study suggests that the in vivo efficacy of SXT in treating diarrheal illness be reevaluated.

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