• Title/Summary/Keyword: Drug-associated

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Development of Korean Food-Chemical Ranking and Scoring System (Food-CRS-Korea) and Its Application to Prioritizing Food Toxic Chemicals Associated with Environmental Pollutants (환경유래 식품오염물질의 우선순위 선정 기법 (Food-CRS-Korea)의 개발과 적용)

  • Yang, Ji-Yeon;Jang, Ji-Young;Kim, Soo-Hwaun;Kim, Yoon-Kwan;Lee, Hyo-Min;Shin, Dong-Chun;Lim, Young-Wook
    • Environmental Analysis Health and Toxicology
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    • v.25 no.1
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    • pp.41-55
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    • 2010
  • The aims of this study were to develop the suitable "system software" in chemical ranking and scoring (CRS) for the food hazardous chemicals associated with environmental emission and to suggest the priority lists of food contamination by environmental-origined pollutants. Study materials were selected with reference to the priority pollutants list for environment and food management from domestic and foreign research and the number of study materials is 103 pollutants (18 heavy metals, 10 PBTs, 10 EDs, and 65 organic compounds). The Food-CRS-Korea system consisted of the environmental fate model via multimedia, transfer environment to food model, and health risk assessment by contaminated food intake. We have established that health risks of excess cancer risks, hazard quotients (HQs) by chronic toxicity and HQs by reproductive toxicity convert to score, respectively. The creditable scoring system was designed to consider uncertainty of quantitative risk assessment based on VOI (Value-Of-Information). The predictability of the Food-CRS-Korea model was evaluated by comparing the presumable values and the measured ones of the environmental media and foodstuffs. The priority lists based on emissions with background-level-correction are 15 pollutants such as arsenic, cadmium, and etc. The priority lists based on environmental monitoring date are 17 pollutants including DEHP, TCDD, and so on. Consequently, we suggested the priority lists of 13 pollutants by considering the several emission and exposure scenarios. According to the Food-CRS-Korea system, arsenics, cadmium, chromes, DEHP, leads, and nickels have high health risk rates and reliable grades.

The Clinical Evaluation in Cancer Pain Management (암성통증환자의 통증완화법과 실태에 대한 연구)

  • Baik, Seong-Wan;Byeun, Byeung-Ho;Chae, Myoung-Gil
    • The Korean Journal of Pain
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    • v.11 no.2
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    • pp.214-219
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    • 1998
  • Pain is one of the most frequent and disturbing symptom of cancer patients. And almost of cancer patients are afraid of a attacks of pain related to cancer. Caring for the cancer patient can be divided into two phases. The phase of "active treatment" involves various interventions-surgical, chemical or radiological- that are designed to prolong the patient's life. "Terminal care" is the period from the end of active treatment until the patient's death. But in the majority of clinical settings, cancer pain is not being managed adequately results from a lack of education about how to treat the cancer pain management in the safest and most effective way during terminal phase. Althought organic factors represent the most important cause of their pain, it is also important to deal with the patient's psychological reactions and to take account of his or her social and family environment if treatment for chronic cancer pain is to prove adequate. Thus we try to evaluate a kinds of cancer related to pain, degree of pain, effectiveness of drugs, and patient's responses to management. In regard to the satisfaction for pain relief in pain clinics at Pusan National University Hospital(PNUH) are about 70% in patients and 90% in family. Average life expectancy in cancer patients are about 140 days (3 days- 5.7 years). Cancer patients are complained of several discomfortness (above 30 kinds) such as, pain associated with cancer (75%), nausea and vomitting (38%), sleeping disorder (38%), anorexia (38%), dyspnea (32%), constipation (31%), etc. Distributions of cancer associated with pain are stomach cancer (21%), lung cancer (16%), cervix cancer (10%), anorectal and colon cancer (8.6%), hepatoma (8%), pancreatic cancer (3%). About 1/3 of patients are suffer from incident pain in 3~5 times in a day especially in moving, coughing, and exercise. Methods for drug delivering system before death are transdermal fentanyl patch (42%), intravenous PCA (21%), oral intake of opioid (17%), epidural PCA (14%), etc.

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A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy

  • Sil, Amrita;Kumar, Hrishikesh;Mondal, Rahul Deb;Anand, Sidharth Sankar;Ghosal, Anirban;Datta, Ashis;Sawant, Sandesh V;Kapatkar, Vaibhavi;Kadhe, Ganesh;Rao, Sameer
    • The Korean Journal of Pain
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    • v.31 no.3
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    • pp.183-190
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    • 2018
  • Background: Vitamin B12 deficiency has been associated with peripheral neuropathy, loss of sensation in the peripheral nerves, and weakness in the lower extremities. Methylcobalamin is the most effective analogue of vitamin B12 used to treat or prevent the complications associated with vitamin B12 deficiency. The current study aimed to compare the serum cobalamin levels after administration of two different regimes of methylcobalamin in peripheral neuropathy patients. Methods: The present study was a prospective, randomized, comparative study. The study consisted of two parallel groups, group A (methylcobalamin $500{\mu}g$ injection intramuscularly three times a week) and group B (methylcobalamin $1500{\mu}g$ injection intramuscularly once a week). A control group of healthy volunteers was also included. Results: A total of 24 patients (12 in each group) were included in the study. Five healthy volunteers were also included as a control in each group. At the end of treatment, serum cobalamin levels were significantly (P = 0.028) higher in group A ($1892.08{\pm}234.50$) as compared with group B ($1438.5{\pm}460.32$). The serum cobalamin levels in Group A healthy volunteers were also two times higher than that of group B (P = 0.056). Both the LANSS scale and DN4 questionnaire reported similar results at end of treatment. Conclusions: The $500{\mu}g$ methylcobalamin thrice weekly regime is more effective in increasing the serum cobalamin levels as compared to the $1500{\mu}g$ methylcobalamin once weekly regime.

What Should Be Considered to Cause the Early Post-Craniotomy Seizure : Antibiotics (Cefazolin) Irrigation

  • Jang, Ji Hwan;Song, Kyung Sun;Bang, Jae Seung;Oh, Chang Wan;Kwon, O-Ki;Chung, Young Seob
    • Journal of Korean Neurosurgical Society
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    • v.58 no.5
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    • pp.462-466
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    • 2015
  • Objective : Post-craniotomy seizure (PCS) is reported only rarely. However, our department noted a 433% increase in PCS for a year beginning September 2010, especially after cerebrovascular surgery. Our goal was to identify the cause of our unusual outbreak of PCS. Methods : For almost one year after September 2010, cases of PCS increased significantly in our department. We analyzed 973 patients who had received a major craniotomy between January 2009 and November 2011. We included seizures that occurred only in the first 24 postoperative hours, which we defined as early PCS. After verifying the presence of PCS, we analyzed multiple seizure-provoking factors and their relation to the duration and character of seizure activity. Results : Overall PCS incidence was 7.2% (70/973). Cefazolin (2 g/L saline) was the antibiotic drug used for intraoperative irrigation in 88.4% of the operations, and no PCS occurred without intraoperative cefazolin irrigation. When analyzed by operation type, clipping surgery for unruptured aneurysms was the most frequently associated with PCS (80%). Using logistic regression, only 2 g cefazolin intraoperative irrigation (p=0.024) and unruptured aneurysm clipping surgery (p<0.001) were associated with early PCS. The seizure rate of unruptured aneurysm clipping surgery using 2 g cefazolin intraoperative irrigation was 32.9%. Conclusion : Intraoperative cefazolin irrigation must be avoided in patients undergoing craniotomy, especially for clipping of unruptured aneurysms, because of the increased risk of early PCS.

β-Elemene Induces Apoptosis in Human Renal-cell Carcinoma 786-0 Cells through Inhibition of MAPK/ERK and PI3K/Akt/mTOR Signalling Pathways

  • Zhan, Yun-Hong;Liu, Jing;Qu, Xiu-Juan;Hou, Ke-Zuo;Wang, Ke-Feng;Liu, Yun-Peng;Wu, Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2739-2744
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    • 2012
  • Background: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. ${\beta}$-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. Methods: Human RCC 786-0 cells were treated with different concentrations of ${\beta}$-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy. Results: ${\beta}$-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that ${\beta}$-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with ${\beta}$-elemene. Combined treatment of ${\beta}$-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects. Conclusions: Our data provide first evidence that ${\beta}$-elemene can inhibit the proliferation of RCC 786-0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of ${\beta}$-elemene on 786-0 cells.

Participation of $K_{ATP}$ Channels in the Antinociceptive Effect of Pregabalin in Rat Formalin Test

  • Kweon, Tae-Dong;Kim, Ji-Young;Kwon, Il-Won;Choi, Jong-Bum;Lee, Youn-Woo
    • The Korean Journal of Pain
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    • v.24 no.3
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    • pp.131-136
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    • 2011
  • Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

  • Ha, Ye-Na;Sung, Hye Youn;Yang, San-Duk;Chae, Yun Ju;Ju, Woong;Ahn, Jung-Hyuck
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.1
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    • pp.43-51
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    • 2018
  • Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified ${\alpha}$-N-acetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly down-regulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

Clinical study on 1 case of Hemichorea-Hemiballism patients with Diabetes mellitus treated by Saamchimbeop Ganjeonggyeok (당뇨를 동반한 편측 무정위 운동(Hemichorea-Hemiballism) 환자에 대한 사암침법 간정격 치험 1례)

  • Park, Sang-min;Kang, Jung-won;Kim, Dong-hoon;Kim, Jong-deog;Yin, Chang-shik;Woo, Hyun-su;Seo, Dong-min;Lee, Sang-hoon;Kang, Sung-keel;Lee, Jae-dong
    • Journal of Acupuncture Research
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    • v.20 no.4
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    • pp.230-236
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    • 2003
  • Objective : Hemichorea-Hemiballism is a violent, involuntary movement restricted to one side of the body. It is usually associated with stroke, and infrequently associated with infections, drug usage, metabolic derangement, and hyperglycemia. In this study, we performed to evlauate the effects of Saamchimbeop Ganjeonggyeok on the the 1 case of Hemichorea-Hemiballism with diabetes mellitus. Methods : We performed Saamchimbeop Ganjeongyeok which consists of KI10(陰谷), LR8(曲泉), LU8(經渠), LR4(中封). The effect of Saamchimbeop was assessed by comparing the counts of the movements of ankle and metatarsal joint for 1 minutes before and after acupuncture therapy. Results : The hemiballismic movements was reduced after acupuncture therapy. Conclusions : The Saamchimbeop was effective on the patient of Hemichorea-Hemiballism with diabetes mellitus. And Further studies with more population are necessary.

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Quantitative Assessment of the Association between ABC Polymorphisms and Osteosarcoma Response: a Meta-analysis

  • Chen, Xu;Jiang, Min;Zhao, Rui-Ke;Gu, Guo-Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4659-4664
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    • 2015
  • Background: ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. TC/CC: OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

Integrative Meta-Analysis of Multiple Gene Expression Profiles in Acquired Gemcitabine-Resistant Cancer Cell Lines to Identify Novel Therapeutic Biomarkers

  • Lee, Young Seok;Kim, Jin Ki;Ryu, Seoung Won;Bae, Se Jong;Kwon, Kang;Noh, Yun Hee;Kim, Sung Young
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2793-2800
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    • 2015
  • In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies.