• Title/Summary/Keyword: Drug toxicity

Search Result 707, Processing Time 0.026 seconds

Physiological Activity of Supercritical Poria cocos back Extract and Its Skin Delivery Application using Epidermal Penetrating Peptide (초임계 복령피 추출물의 생리활성 및 경피투과 펩티드를 이용한 경피 약물전달의 응용)

  • Kim, Min Gi;Park, Su In;An, Gyu Min;Heo, Soo Hyeon;Shin, Moon Sam
    • Journal of the Korean Applied Science and Technology
    • /
    • v.36 no.3
    • /
    • pp.766-778
    • /
    • 2019
  • In this study, Poria cocos bark were extracted by supercritical process, and anti-inflammatory, whitening, and antioxidant effects were measured in comparison with ethanol extract. Also, An effective percutaneous permeation method using a selected formulation of the extract and a drug delivery peptide was proposed. Pachymic acid, known as the anti-cancer and anti-inflammatory compound of the ventricle, is an indicator component and the HPLC analysis shows that the supercritical extract of the pericardium is more than twice that of the Poria cocos bark extract. In order to confirm antioxidative effect of Bombyx mori, DPPH scavenging ability and ABTS scavenging ability test showed that the ethanol extract of Poria cocos Back had lower concentration than the supercritical extract of Poria cocos back. However, RAW 264.7 Measurements of Nitric oxide (NO) production in cells showed lower NO production at the same concentration than the Poria cocos back ethanol extract. In addition, after 72 hours of processing of $20{\mu}g/mL$ of the Poria cocos back extract in B16 melanoma cells, both the intracellular and extracellular melanin extract were effective and the supercritical extract was lower melanin content. No toxicity was observed at the concentration of $800{\mu}g/mL$ in RAW 264.7 cells used in NO production experiments. However, in B16 melanoma cells, even at $50{\mu}g/mL$, both Poria cocos back ethanol extract and supercritical extract showed a survival rate of less than 60%. The liposome formulation and drug delivery peptides were shown to be useful for percutaneous permeation of Supercritical Extract of Poria cocos back using a liposome formulation and a drug delivery peptide. it is expected that there will be great potential for development as a variety of cosmetic materials for Poria cocos back.

Pharmacokinetics of amikacin in plasma of healthy goats after intravenous injection once daily for three days

  • Naseem, Sania;Sultana, Mudasir;Raina, Rajinder;Pankaj, Nrip Kishore;Verma, Pawan Kumar;Nasir, Nasir Ahmad;Ahanger, Azad Ahmad;Rahman, Shafiqur;Prawez, Shahid
    • Korean Journal of Veterinary Research
    • /
    • v.51 no.4
    • /
    • pp.253-257
    • /
    • 2011
  • Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean ${\pm}$ SD) of amikacin at time zero ($Cp^{0}$) was $114.19{\pm}20.78$ and $128.67{\pm}14.37{\mu}g/mL$, on day 1st and 3rd, respectively. The mean elimination half-life ($t_{1/2}ke$) was $1.00{\pm}0.28h$ on day 1st and $1.22{\pm}0.29h$ on day 3rd. Mean of area under concentration-time curve ($AUC_{0{\rightarrow}{\infty}}$) was $158.26{\pm}60.10$ and $159.70{\pm}22.74{\mu}g.h/mL$, on day 1st and 3rd respectively. The total body clearance ($Cl_{B}$) and volume of distribution at steady state (Vdss) on day 1st and 3rd were $Cl_{B}=0.07{\pm}0.02$ and $0.06{\pm}0.01L/h.kg$ and $Vdss=0.10{\pm}0.03$ and $0.11{\pm}0.05L/kg$, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.

Genistein Suppresses TPA-Induced Matrix Metalloproteinases Activity and Cell Invasion in Human Breast Adenocarcinoma Cells (인체 유방암세포에서 TPA에 의해 유도된 matrix metalloproteinases 활성 및 침윤성 증대에 미치는 genistein의 영향)

  • Choi, Yung-Hyun;Kim, Sung-Ok
    • Journal of Life Science
    • /
    • v.22 no.7
    • /
    • pp.964-969
    • /
    • 2012
  • Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

Guideline of Improvement and Evaluation of Prescribing Errors in Colorectal Chemotherapy (대장암 항암 화학요법의 처방 오류 평가 및 개선안 제시)

  • Lim, Hyun-Soo;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
    • /
    • v.23 no.2
    • /
    • pp.158-166
    • /
    • 2013
  • Background: Colorectal cancer shows a significant increase in South Korea due to westernization of diet, lack of dietary fiber, drinking and smoking, irregular defecation. There are surgery, chemotherapy, radiation therapy in treatment of colorectal cancer. There may be a medication errors in the process of chemotherapy because of its high toxicity, narrow therapeutic index and the health status of cancer patients. Consequently medication errors can cause increasing the risk of death, prolonging hospital stay and increasing the cost. Among medication errors on medication use process, prescribing errors are of particular concern due to higher risk of serious consequences. It is important for pharmacist to prevent the prescribing errors before reaching patient. Therefore we analyzed the prescriptions of colorectal cancer, classified prescribing errors, suggested guideline to reduce prescribing errors and verified the importance of pharmacist's role in prevention of medication errors activity. Methods: We collected the numbers of prescriptions of colorectal cancer(n=2,373) through anti cancer management program and EMR and analyzed the errors of prescriptions by categories from Oct 1st 2011 to Sep 30th 2012 at Chungbuk National University Hospital. We reviewed the prescriptions as follows - patients' characteristics, the result of test, previous prescriptions, characteristics of antineoplastic agents and patients' allergy, drug sensitivity, adverse events. Prescriptions are classified into inpatient and outpatient and analyzed the errors of prescriptions by categories (dosage form, dose, input, diluents, regimen, product). Results: Total prescription number of inpatient and outpatient of colorectal cancer was 1,193 and 1,180 and that of errors was 107(9%) and 22(1.9%), respectively. In case of errors of categories, the number of errors of dosage form is 69 and 8, errors of dose is 15 and 5, errors of input is 9 and 9 in inpatient and outpatient prescriptions, respectively. Errors of diluents is 8, errors of regimen is 3, errors of product is 3 in only inpatient prescriptions. In case of errors of categories by inpatient department, the number of errors of dosage form is 34 and 35, errors of dose is 7 and 8, errors of input is 6 and 3, errors of diluents is 4 and 4, errors of regimen is 2 and 1, errors of product is 2 and 1 in SG and HO, respectively. In case of outpatient department, the number of errors of dosage form is 8 in HO, errors of dose is 5 in HO, errors of input is 5 and 4 in SG and HO, respectively. Conclusions: The rate of errors of inpatient is higher than that of outpatient. Junior doctors are engaged in prescriptions of inpatient and pharmacist need to pay attention to review all prescriptions. If prescribing errors are discovered, pharmacist should contact the prescriber and correct the errors without delay. The guideline to reduce prescribing errors might be upgrading software of anti cancer management program, education for physicians as well as pharmacists and calling prescriber's attention to preventing recurrence of errors.

Medication Errors in Chemotherapy Preparation and Administration: a Survey Conducted among Oncology Nurses in Turkey

  • Ulas, Arife;Silay, Kamile;Akinci, Sema;Dede, Didem Sener;Akinci, Muhammed Bulent;Sendur, Mehmet Ali Nahit;Cubukcu, Erdem;Coskun, Hasan Senol;Degirmenci, Mustafa;Utkan, Gungor;Ozdemir, Nuriye;Isikdogan, Abdurrahman;Buyukcelik, Abdullah;Inanc, Mevlude;Bilici, Ahmet;Odabasi, Hatice;Cihan, Sener;Avci, Nilufer;Yalcin, Bulent
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.5
    • /
    • pp.1699-1705
    • /
    • 2015
  • Background: Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience. Materials and Methods: This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data. Results: Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%). Conclusions: Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures and establishing multistep control mechanisms.

Genotoxicity on $21{\alpha}-and\;{\beta}-methylmelianodiol$, a Component of Poncirus trifoliata, in Bacterial and Mammalian Cells

  • Ryu, Jae-Chun;Kim, Youn-Jung;Kim, Mi-Soon;Kim, Min-Ji;Sarma, Sailendra Nath;Lee, Seung-Ho
    • Molecular & Cellular Toxicology
    • /
    • v.1 no.3
    • /
    • pp.172-178
    • /
    • 2005
  • [ $21{\alpha}$ ]- and ${\beta}$-Methylmelianodiol were isolated as the inhibitor of IL-5 bioactivity from Poncirus tripoliata. To develope as an anti-septic drug, the genotoxicity of $21{\alpha}\;-and\;{\beta}-methylmelianodiol$ was subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of $21{\alpha}-methylmelianodiol$ was determined the concentration of $25.51\;{\mu}g/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. Also $21{\beta}-methylmelianodiol$ was determined the concentration of $24.15\;{\mu}g/mL\;and\;\;22.46\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, DNA damage was not observed both $21{\alpha}-methylmelianodiol\;and\;21{\beta}-methylmelianodiol$ in mouse lymphoma cell line. Also, the mutant frequencies in the treated cultures were similar to the vehicle controls, and none of $21{\alpha}\;-and\;{\beta}-methylmelianodiol$ with and without S-9 doses induced a mutant frequency over. twice the background. It is suggests that $21{\alpha}\;-and\;{\beta}-methylmelianodiol$ are non-mutagenic in MOLY assay. The results of this battery of assays indicate that $21{\alpha}\;-and\;{\beta}-methylmelianodiol$ have no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that $21{\alpha}\;-and\;{\beta}-methylmelianodiol$, as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen.

Imipramine enhances neuroprotective effect of PEP-1-Catalase against ischemic neuronal damage

  • Kim, Dae-Won;Kim, Duk-Soo;Kim, Mi-Jin;Kwon, Soon-Won;Ahn, Eun-Hee;Jeong, Hoon-Jae;Sohn, Eun-Jeong;Dutta, Suman;Lim, Soon-Sung;Cho, Sung-Woo;Lee, Kil-Soo;Park, Jin-Seu;Eum, Won-Sik;Hwang, Hyun-Sook;Choi, Soo-Young
    • BMB Reports
    • /
    • v.44 no.10
    • /
    • pp.647-652
    • /
    • 2011
  • The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1-CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by $H_2O_2$. Additionally, the group of PEP-1-CAT + imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT + imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders.

Protective Effects of Succinic Acid of Succiniter against Liver Toxicity (간 독성에 대한 보석 호박 호박산의 간 보호 효과)

  • Kim, Hong-Bi;Ha, Bae-Jin
    • Journal of Life Science
    • /
    • v.27 no.8
    • /
    • pp.896-901
    • /
    • 2017
  • This study was performed to investigate the protective effects of succinic acid of Succiniter against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. After an adaptation period of one week, Sprague-Dawley rats were administered succinic acid of Succiniter at 200 mg/kg every day for 21 days. Then $CCl_4$ (3.3 ml/kg) was intraperitoneally injected into rats of the other groups except the normal group, five hours after the last treatment of succinic acid of Succiniter on day 21. The succinic acid-treated group showed 93.20% and 88.76% of inhibitory effects in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, respectively, compared with the $CCl_4-treated$ group. The succinic acid-treated group showed inhibition of malonedialdehyde (MDA) by 85.17% compared with the $CCl_4-treated$ group. The succinic acid-treated group in liver homogenate promoted effects of 38.65% and 47.99% in superoxide dismutase (SOD) and catalase (CAT), respectively, compared with the $CCl_4-treated$ group. In conclusion, the AST and ALT activities of the succinic acid-treated group were both decreased compared with the $CCl_4-treated$ group. The MDA level of the succinic acid-treated group was decreased compared with the $CCl_4-treated$ group. However, the SOD and CAT levels of the succinic acid-treated group in liver homogenate were both increased compared with the $CCl_4-treated$ group. Also, histological examinations showed that the liver cell necrosis and centrilobular congestion aggregation induced by $CCl_4$ were clearly eliminated by treatment with succinic acid of Succiniter. These results suggest that succinic acid of Succiniter has a protective effect against liver damage and could be used in the development of the appropriate drug.

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
    • /
    • v.36 no.1
    • /
    • pp.17-24
    • /
    • 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.

DNA and Proteomic Analysis of Ginseng Radix Rubra Herbal-acupuncture Solution(GRR-HAS) on Gene Expression in HepG2 Carcinomar Cells (홍삼약침액(紅蔘藥鍼液)의 DNA와 단백질 발현(發顯)에 미치는 영향(影響))

  • Won, Eun-Ju;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul;Lee, Kyung-Min
    • Journal of Acupuncture Research
    • /
    • v.23 no.3
    • /
    • pp.177-190
    • /
    • 2006
  • Objectives : It has long been known about the anticancer effect of GRR-HAS, however, it has not been systemically determined the differentially regulated genes by GRR-HAS in cancer cells. The purpose of this study is to screen the GRR-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cell lines. Oligonucleotide microarray and proteomic approaches were employed to screen the differential expression genes. Methods : GRR~HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of GRR-HAS (0.1, 0.5, 1.5, 10, $20mg/m{\ell}$) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with $1.5mg/m{\ell}$ of GRR-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 cells in all concentrations(0.1, 0.5, 1.5, 10,$20mg/m{\ell}$). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 320 with 6 up-regulated and 314 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. One down -regulated protein was protein disulfide isomerase and up-regulated proteins were fatty acid binding protein 1 and 14-3-3 gan1lTIa protein by $1.5mg/m{\ell}$ of CRR-HAS. Discussion : This study showed the comprehensive gene expression analysis using oligonucleotide microarray for the screening of GRR-HAS mediated differentially regulated genes. These results will provide a better application of GRR-HAS in cancer field and drug target development.

  • PDF