• Title/Summary/Keyword: toxicity

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A Case of Ischemic Colitis Associated with Paclitaxel Loaded Polymeric Micelle ($Genexol-PM^{(R)}$) Chemotherapy

  • Park, Choel-Kyu;Kang, Hyun-Wook;Kim, Tae-Ok;Ki, Ho-Seok;Kim, Eun-Young;Ban, Hee-Jung;Yoon, Byeong-Kab;Oh, In-Jae;Choi, Yoo-Deok;Kwon, Yong-Soo;Kim, Yoo-Il;Lim, Sung-Chul;Kim, Young-Chul;Kim, Kyu-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.2
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    • pp.115-118
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    • 2010
  • Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.

Oxaliplatin-induced Peripheral Neuropathy in Patients with Advanced or Metastatic Gastric Cancer (진행성 또는 전이성 위암 환자에 있어서 Oxaliplatin 투여로 인한 말초신경통증 분석)

  • Park, Ae-Ryoung;Kim, Soon-Joo;Bang, Joon-Seok;La, Hyen-Oh
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.18-22
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    • 2009
  • Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

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Effect of $SLCO1B1^*15$ on Pravastatin Pharmacokinetics: A Systematic Review and Meta-analysis (프라바스타틴에서 $SLCO1B1^*15$의 약동학적 영향: 체계적 고찰 및 메타분석)

  • Kim, Jong Yoon;Nakagawa, Naoto;Yoon, Hyonok;Chun, Pusoon;Rhew, Ki Yon
    • Korean Journal of Clinical Pharmacy
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    • v.24 no.4
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    • pp.231-239
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    • 2014
  • Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

A study on the Formulation of high-moisturizing Cosmetics containing Ulmus davidiana supercritical fluid extract (초임계 추출 느릅나무 성분을 함유한 고 보습 화장품 제형에 대한 평가 연구)

  • Gu, Eun-Bi;Kim, Han-Gyu;Kim, Yun-Sik;Choo, Eui-Jin
    • Journal of the Korea Convergence Society
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    • v.11 no.5
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    • pp.241-251
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    • 2020
  • This study was performed to develop the cosmetics containing extract of U.davidiana, which has been confirmed as a functional ingredient of anti-microbial, anti-oxidant, and anti-inflammatory effects, and also to evaluate the improvement effects of dry and sensitive skin such as atopic dermatitis. Toxicity tests of the Ulmus davidiana supercritical fluid residue 60% EtOH extracts(USCFR), Ulmus davidiana supercritical fluid extracts(USCF) and preliminary formulations, DKBP-1903(gel), containing the USCFR and USCF were determined to be 'Non-toxic'. Based on this, the stability test of the lotion, cream, gel formulation was conducted and the results showed that cream and gel formulation were stable. A 48-hour moisturizing sustainability test and the improvement test on the pruritus caused by dryness were selected for the cosmetic efficacy test to evaluate the improvement of atopic dermatitis and as a result both cream and gel have been found to be relatively safe moisturizers that can help dry and sensitive skin.

Paralytic Shellfish Poison Profile in Commercial Shellfishes (시판 중인 패류의 마비성 패류독 특성)

  • Jang, Jun-Ho;Yun, So-Mi;Lee, Jong-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.6
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    • pp.924-928
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    • 2005
  • Toxin profiles of the paralytic shellfish poison (PSP) detected from domestic shellfishes collected at the market and imported. shellfishes were invested by fluorometric HPLC. Total 9 components in PSP were analysed from the imported ark shell, such as saxitoxin (STX), decarbamoylsaxitoxin (dcSTX), gonyautoxin (GTX) - 1,2,3,4,5, Cl and C2. Among those toxins, 7 components except for GTX1,4 were detected from domestic shellfishes and showed different toxin contents and toxin compositions by species. Only C group toxin (Cl +2) contained in short necked clam and hard clam $(0.06\~0.56\;nmole/g)$ which living under soil but, in the blue mussels and oysters which cultured in the open sea water, showed more higher toxicity and complicate toxin compositions. Toxin compositions in bloody clam and purplish washington clam were very different in some samples even in same species. GTX4 and GTX5 were higher in imported scallop and STX was higher in imported ark shell than other species.

Antioxidant and Anti-Inflammatory Effects of Kamisipjeondaebotang in RAW 264.7 Cells (가미십전대보탕의 RAW 264.7 세포에서 항산화 및 항염증 효과)

  • Myung, Jeong-Ho;Lee, Myung-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1271-1277
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    • 2017
  • As Kamisipjeondaebotang (KSD) extract is an herbal ingredient, safety is very important due to possible cell poisoning or heavy metal toxicity to organs when administered to humans or animals. Accordingly, this study examined the antioxidant and anti-inflammatory effects of KSD extract to confirm its medicinal safety by using RAW 264.7 cells after heavy metal screening, functional index test of the liver and kidney, and cell survival rate test. Heavy metals were not found in KSD extracts or were less than standard amounts. Liver function indices such as aspartate aminotransferase and alanine aminotransferase revealed low values and kidney function indices such as creatinine and blood urea nitrogen were not significantly different from the normal group. This proved the safety to the human. RAW 264.7 cells showed no poisoning compared to the control group in terms of survival rate. Regarding the antioxidant effect of KSD extract, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazo-line-6-sulphonic acid) radical scavenging activity increased at concentrations over $10{\mu}g/mL$. The anti-inflammatory effect of KSD extract significantly decreased based on the amount of nitric oxide at concentrations of 10 and $100{\mu}g/mL$ compared to the control group. Expression of interleukin (IL)-$1{\beta}$ and IL-6 decreased in a concentration-dependent manner. There was no significant difference in tumor necrosis factor-${\alpha}$ level. Based on the results, KSD can be regarded as a safe antioxidant with anti-inflammatory effects for fracture treatment.

Effects of fermented Taraxacum mongolicum by Dongchimi on protection of liver cell and immune activity (포공영(민들레)의 동치미 발효에 의한 간세포 보호 및 면역증진 효과)

  • Choi, Bog-Soo;Kim, Hye-Ja
    • Journal of Society of Preventive Korean Medicine
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    • v.18 no.1
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    • pp.11-21
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    • 2014
  • Objective : This study set out to combine the treatment efficacy of Taraxacum with Dongchimi fermentation and investigate Taraxacum's effects on protection of liver cell and controlling nitric oxide(NO) through experiments, thus checking whether it had values as a physiological active matter. The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anticancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Method : The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anti-cancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Results : As shown in the chromatogram results, each valid component content increased in Taraxacum fermented by Dongchimi (TDF) for each time section. Of them, the valid component content at 36.80 minutes was approximately 2.7 times higher in TDF at 21.8% than in Taraxacum Dongchimi (TD) at 8.28%. TDF generated more excellent protection effects against the toxicity that caused oxidative damage to the liver cell(HepG2) with t-BHP than TD. The survival rate was low in TD of $100{\mu}g/m{\ell}$ and $300{\mu}g/m{\ell}$ and increased to 23.3% in TDF of $100{\mu}g/m{\ell}$. The survival rate was the highest at $300{\mu}M$ with a significant difference of 68.1%(P<0.05). Both TD and TDF showed effects of controlling nitric oxide production according to concentration with TDF recording a higher rate of controlling nitric oxide production than TD. There were significant differences(P<0.05) in the effects of controlling nitric oxide production at 200 ug/ml, 400 ug/ml in both groups. Especially the result TDF of $400{\mu}g/m{\ell}$ was thus similar to those of butein, the positive control group. Conclusion : The result of this studies is that Taraxacum fermented by Dongchimi (TDF) increased the valid component content compared with the simple mixture(TD). The findings clearly show that it is a material with the effects of improving immunity and liver cell protection. If fermentation methods are further developed to use it as a functional material, it will be subject to more opportunities of being used in other functional foods and make a contribution to integrated medicinal food development.

The Protective Effects of Salicornia herbacea L. against Liver Toxicity (함초의 간독성에 대한 보호효과)

  • Ha, Bae-Jin;Lee, Sang-Hun
    • Journal of Life Science
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    • v.16 no.1
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    • pp.95-100
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    • 2006
  • This study was carried out to investigate the effects of Salicornia herbacea L. (SH) on carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity. Sprague-Dawley rats were intraperitoneally administered the SH at 100 mg/kg per day for two weeks. Then single dose of $CCl_4$ (3.3 ml/kg) was injected into rats. Twelve hours later, they were anesthesized with ether and dissected. $SH-CCl_4-administered$ group showed $65.56\%\;and\;59.04\%$ of inhibitory effects in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, compared to $CCl_4-treated$ group (p<0.05). Malonedialdehyde (MDA) levels of $SH-CCl_4-administered$ group in liver homogenate and mitochondria were significantly inhibited by $53.74\%,\;89.86\%$, and respectively, compared to $CCl_4-treated$ group (p<0.05). Superoxide dismutase (SOD) activities of $SH-CCl_4-administered$ group in liver homogenate and mitochondria were significantly inhibited by $42.51\%,\;and\;38.42\%$, respectively, compared to $CCl_4-treated$ group (p<0.05). The histological examinations showed that the liver cell necrosis and centrilobular congestive aggregation induced by $CCl_4$ were clearly eliminated by the administration of SH. These results suggest that SH could have the protective effects against hepatotoxicity.

Study of Macrophage Stimulating Activity of the Polysaccharide Isolated from Leaves of Carthamus tinctorius L. (홍화(Carthamus tinctorius L.)잎으로부터 분리한 다당류의 Macrophage 활성화에 대한 연구)

  • Kwak, Ji-Eun;Kim, Kyung-Im;Jeon, Hyuck;Hong, Bum-Shick;Cho, Hong-Yon;Yang, Han-Chul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.3
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    • pp.527-533
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    • 2002
  • In the screening of Korean traditional tea sources for the cellular lysosomal enzyme activity of peritoneal macrophage from mice, CT-0, a cold-water extract from Carthamus tinctorius L., showed the highest macro-phage-stimulating activity. CT-1-IIa-2-1, a purified macrophage-stimulation polysaccharide was obtained by a series of purification steps such as anion exchage chromatography with DEAE-Toyopearl 650M, gel permeation chromatography with Sepharose CL-6B, Sephacryl S-200, and HPLC with Superdex G-75. The molecular weight of homogeneous purified polysaccharide was estimated about 68 kDa. CT-1-IIa-2-1 consisted of xylose 27.44%, arabinose 16.14%, mannose 15.92% and glucose 14.47%. To measure acute toxicity, dose of 50, 100, 500, and 1000 mg/kg were intraperitoneally injected to ICR mice. The LD$\_$50/ was about 397 mg/kg.

DNA and Proteomic Expression of Cervi parvum cornu Herbal-acupuncture Solution (CPC-HAS) in HepG2 carcinomar cells (녹용약침액(鹿茸藥鍼液)의 간암세포주(肝癌細胞柱)에 대한 DNA 및 단백질 발현(發顯))

  • Ryu, Sung-Hyun;Lee, Kyung-Min;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul
    • Journal of Pharmacopuncture
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    • v.9 no.2
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    • pp.5-16
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    • 2006
  • Objective : It has long been known about the osteogenic effect of CPC-HAS on bone tissues. However, it has not been determined the effect of CPC-HAS on cancer cells. The purpose of this study is to screen the CPC-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cells. Oligonucleotide microarray and proteomics approaches were employed to screen the differential expression genes. Methods : CPC-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of CPC-HAS (0.1, 0.5, 1.5, 10, 20mg/ml) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with 1.5mg/ml of CPC-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide Genechip(Human genome Ul33 Plus 2.0., Affimatrix Co.). For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : It has no cytotoxic effects on both HepG2 cell in all concentrations(0.l, 0.5, 1.5, 10, 20mg/ml). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 23 with 5 up-regulated and 18 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. Two down-regulated proteins were aldehyde dehydrogenase 1 and enolase 1, and up-regulated protein was fatty acid binding protein 1 by 1.5mg/ml of CPC-HAS. Discussion : This study showed the screening of CPC-HAS mediated differentially regulated genes using combined approaches of oligonucleotide microarray and proteomic analysis. The screened genes will be used for the better understanding of the therapeutic effects of CPC-HAS on cancer fields.