• Title/Summary/Keyword: Drug response

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The experimental study on the anti-allergic effects of Ursi fel and Ursodesoxycholic acid (UDCA) (웅담(熊膽) 및 우루소데옥시콜린 산(酸)의 항(抗)알레르기 효과(效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Jeong Jae-Hwan;Lee Jin-Yong;Kim Deok-Gon;Jeong Gyu-Man
    • The Journal of Pediatrics of Korean Medicine
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    • v.10 no.1
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    • pp.299-321
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    • 1996
  • Experimental studies were done to research the effects of the Ursi fel and the UDCA on the anti-allergic effects. The results were obtained as follows: 1) In the experimental effects of the Ursi fel and the UDCA on the vascular permeability responses to intradermal Serotonin, though both of the Ursi fel and UDCA revealed the significant effect, the Ursi fel had stronger effect than the UDCA. 2) In the provocative effects of the Ursi fel and the UDCA on the vascular permeability responses to intradermal Histamin, though both of the Ursi powfel and UDCA showed the significant effect, the Ursi fel had moreerful effect than the UDCA. 3) In the 48 hours homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against white egg albumin, though both of the Ursi fel and UDCA revealed significant effect, the Ursi fel had stronger effect than the UDCA. 4) In the delayed type hypersensitivity response to Picryl Chlorede, though both of the Ursi fel and UDCA were proved to be effective significantly the Ursi fel showed stronger effect. 5) In the delayed type hypersensitivity responses to Sheep red blood cell, the Ursi fel revealed the significant effect, though the UDCA has no significant effect. According to above results, the Ursi fel was approved it could be used widely as antiallergic drug for immediate and delayed type allergic diseases. Although the UDCA revealed efficacy in immediated type allergic diseases, it had less powerful effects than the Ursi fel and it showed no effects in some experiment of delayed type allergy, so it would be difficult to be used clinically.

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Genotoxicity of Aluminum Oxide ($Al_2O_3$) Nanoparticle in Mammalian Cell Lines

  • Kim, Youn-Jung;Choi, Han-Saem;Song, Mi-Kyung;Youk, Da-Young;Kim, Ji-Hee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.5 no.2
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    • pp.172-178
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    • 2009
  • Nanoparticles are small-scale substances (<100 nm) with unique properties, complex exposure and health risk implications. Aluminum oxide ($Al_2O_3$) nanoparticles (NP) have been widely used as abrasives, wear-resistant coatings on propeller shafts of ships, to increase the specific impulse per weight of composite propellants used in solid rocket fuel and as drug delivery systems to increase solubility. However, recent studies have shown that nano-sized aluminum (10 nm in diameter) can generate adverse effects, such as pulmonary response. The cytotoxicity and genotoxicity of $Al_2O_3$ NP were investigated using the dye exclusion assay, the comet assay, and the mouse lymphoma thymidine kinase (tk$^{+/-}$) gene mutation assay (MLA). IC$_{20}$ values of $Al_2O_3$ NP in BEAS-2B cells were determined the concentration of 273.44 $\mu$g/mL and 390.63 $\mu$g/mL with and without S-9. However IC$_{20}$ values of $Al_2O_3$ NP were found nontoxic in L5178Y cells both of with and without S-9 fraction. In the comet assay, L5178Y cells and BEAS-2B cells were treated with $Al_2O_3$ NP which significantly increased 2-fold tail moment with and without S-9. Also, the mutant frequencies in the $Al_2O_3$ NP treated L5178Y cells were increased compared to the vehicle controls with S-9. The results of this study indicate that $Al_2O_3$ NP can cause primary DNA damage and cytotoxicity but not mutagenicity in cultured mammalian cells.

Anti-diabetic Effects of CCCA, CMESS, and Cordycepin from Cordyceps militaris and the Immune Responses in Streptozotocin-induced Diabetic Mice

  • Yun, Yun-Ha;Han, Shin-Ha;Lee, Seung-Jeong;Ko, Sung-Kwon;Lee, Chong-Kil;Ha, Nam-Joo;Kim, Kyung-Jae
    • Natural Product Sciences
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    • v.9 no.4
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    • pp.291-298
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    • 2003
  • Anti-diabetic effect of various fractions of Cordyceps militaris (CM), CCCA (crude cordycepin containing adenosine), CMESS (ethanol soluble supernatant), and cordycepin were evaluated in streptozotocin (STZ) induced diabetic mice, CMESS showed potent inhibitory activity of 34.7% in starch-loaded mice (2 g/kg) while acarbose as a positive standard exhibited 37.8% of inhibition rate. After 3 days administration (50 mg/kg), cordycepin (0.2 mg/kg), and acarbose (10 mg/kg) dramatically reduced blood glucose level (inhibition ratio: 46.9%, 48.4% and 37.5% respectively). CCCA that has high contents of cordycepin (0.656 mg/4 mg) did not influence on reducing blood glucose level. The proliferation of splenocytes and peritoneal macrophages derived from STZ-induced diabetic mice administered samples were evaluated out by addition of mitogens to see the stability of the usage of these herbal medicines. Proliferation of T-lymphocyte was significantly decreased; while NO production was increased more than two fold to STZ control in the cordycepin-administered group. Changes of serum enzyme levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also evaluated. Cordycepin administered group was appeared to acarbose. We conclude that CMESS and cordycepin may be useful tools in the control of blood glucose level in diabetes and promising new drug as an anti-hyperglycemic agent without defects of immune responses and other side effects.

Comparison of Single Agent Gemcitabine and Docetaxel in Second-Line Therapy for Advanced Stage Non-Small Cell Lung Cancer in a University Hospital in Turkey

  • Yildirim, Fatma;Baha, Ayse;Yurdakul, Ahmet Selim;Ozturk, Can
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7859-7863
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    • 2015
  • Purpose: To compare the efficacy and toxicity of gemcitabine versus docetaxel in a second-line setting of nonsmall cell lung cancer (NSCLC) patients previously treated with platin-based combination chemotherapy. Materials and Methods: We retrospectively evaluated the medical records of 57 patients treated with single agent gemcitabine or docetaxel in second-line setting of advanced NSCLC who received one prior platinum-based therapy. Results: The mean age was $56.7{\pm}8.39$ years with 55 (96.5%) males and two (3.5%) females. Forty of them received docetaxel and 17 gemcitabine. The mean number of chemotherapy cycles was $6.8{\pm}4.0$ in the gemcitabine group, while it was $4.6{\pm}3.0$ in the docetaxel group. Overall response rates were 8% and 12% (P=0.02) for gemcitabine and docetaxel, respectively. The median survival time was 22 versus 21 months for gemcitabine and docetaxel, respectively. The median times to progression were 8 and 5 months. There was no difference between the two groups in terms of incidence of adverse affects (40% vs 47.1%). All of the hematological side effects were grade 1/2. No major toxicity was encountered necessitating stopping the drug for either group. Conclusions: Treatment with gemcitabine demonstrated clinically equivalent efficacy with a significantly improved safety profile compared with those receiving docetaxel in the second-line setting for advanced NSCLC in this study. Based on these results, treatment with gemcitabine should be considered a standard treatment option for second-line NSCLC.

Clinical Observation and Prognostic Analysis of Pemetrexed plus Platinum as First-line Treatment in Patients with Advanced Non-small Cell Lung Cancer

  • Wang, Ji-Ying;Cai, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6267-6271
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    • 2013
  • Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

Simultaneous Analysis of Stimulants and Narcotic Analgesics by Capillary Column Gas Chromatography with Nitrogen Phosphorus Detector (Capillary Column Gas Chromatography/Nitrogen Phosphorus Detector를 이용한 흥분제 및 마약성 진통제의 동시분석에 관한 연구)

  • Lho, Dong-Seok;Shin, Ho-Sang;Kang, Bo-Kyung;Paek, Heang-Kee;Kim, Seung-Ki;Lee, Jeong-Ae;Kim, Young-Lim;Park, Jong-Sei
    • Journal of the Korean Chemical Society
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    • v.35 no.6
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    • pp.659-666
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    • 1991
  • A systematic analysis of 18 stimulants and narcotic analgesics containing nitrogen atom (s) in human urine by gas chromatography with nitrogen phosphorus detector (GC-NPD), is described. The urinary extract with diethyl ether at pH 8.5 showed good recoveries of the drugs and less interference peaks on GC chromatogram. Retention data were standardized by the calculation of relative retention times using diphenylamine as the internal standard. The relative standard deviations of retention times were less than 0.1% for the within-run analyses. The response factor (RRF) of a drug relative to the internal standard was calculated. RRF decreased with increasing number of nitrogen atoms. This technique can be adapted to various analytical toxicology problems.

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Antiviral activity of Herba Patrinea (a Chinese medicinal herb) against respiratory syncytial virus in vitro

  • Li, Hong-Yuan;Li, Shan-Shan;Liu, Dian-Li;Dong, Yan-Mei;Tian, Wen-Jing
    • Advances in Traditional Medicine
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    • v.3 no.2
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    • pp.106-110
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    • 2003
  • Respiratory syncytial virus (RSV) has long been considered an important cause of severe lower respiratory tract infection in infants and young children throughout the world. Unfortunately, no effective treatment of RSV exists. Therefore, New agents are needed to reduce the impact of RSV. We have studied the anti-viral effect of traditional Chinese midicinal herbs for over ten years and find Herba Patrinea (a Chinese medicinal herb) has the anti-RSV effect in vitro. In this study, the Herba Patrinea was extracted with hot water, condensed and sterilized. The cytotoxicity of the aqueous extract was tested by adding the diluted extract directly to HeLa cells and its effect on anti-RSV was estimated by the CPEI assay. As a result, the median cytotoxic concentration $(CC_{50})$ of Herba Patrinea was 32 mg/ ml by morphological observation, the median effective concentration (50% effective concentration, $EC_{50}$) of the Herba Patrinea against replication of the Long strain of RSV in HeLa cells were 1.25 mg/ml. The selectivity index $(SI=CC_{50}/EC{50})$ is 25.6. Moreover, Herba Patrinea gave a dose-dependent response in inhibiting RSV. In time of addition experiment, Herba Patrinea inhibited replication of RSV in HeLa cells when it was added at 0h, 2h, and 4h after virus infection. In summary, the results of this study suggest Herba Patrinea may be a novel anti-RSV drug and it is worthy of further studying.

No Role of Protected Region B of Human Cytochrome P4501A2 Gene (CYP1A2) As an AP-1 Response Element

  • Chung, In-Jae;Jung, Ki-Hwa
    • Archives of Pharmacal Research
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    • v.25 no.3
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    • pp.375-380
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    • 2002
  • Cytochrome P4501A2 (CYP1A2) is a member of the cytochrome P450 family of isozymes involved in the phase I drug metabolism of vertebrates. CYP1A2 is responsible for the activation of a number of aromatic amines to mutagenic and carcinogenic forms. Thus, the level of CYP1A2, which varies among different populations, may determine an individual's susceptibility to these chemicals. We have previously reported on the importance of a cis element named PRB (protected region B) in the regulation of human Cytochrome P4501A2 (CYP1A2) gene, which appeared to act as a positive regulatory element. Closer examination of the PRB sequence (-2218 to -2187 bp) revealed a putative AP-1 binding site, TGACTAA, at -2212 bp (Chung and Bresnick, 1997). To elucidate the role of AP-1 in CYP1A2 regulation, we transiently overexpressed c-Jun and c-Fos transcription factors in human hepatoma HepG2 cells, and examined their influence on the CYP1A2 promoter activity by reporter gene assays. Cotransfection of the c-Jun and the c-Fos expression vectors increased the induced transactivation by five to six fold from the CYP1A2 promoter constructs. However, deletion of the PRB element did not affect the degree of activation by the c-Jun and the c-Fos. Therefore, it is unlikely that the c-Jun and the c-Fos activate the CYP1A2 promoter through this AP-1 consensus-like sequence in the PRB region.

Induction of p53-Dependent G1 Cell Cycle Arrest by Rhus verniciflua. Stokes Extract in Human Breast Carcinoma MCF-7 Cells (MCF-7 인체 유방암 세포에서 옻나무 추출물이 p53-Dependent G1 Cell Cycle에 미치는 영향)

  • Hong, Sang-hoon;Han, Min-ho;Choi, Yung-hyun;Park, Sang-eun
    • The Journal of Internal Korean Medicine
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    • v.36 no.1
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    • pp.13-21
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    • 2015
  • Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

Antileishmanial and Cytotoxic Effects of Essential Oil and Methanolic Extract of Myrtus communis L.

  • Mahmoudvand, Hossein;Ezzatkhah, Fatemeh;Sharififar, Fariba;Sharifi, Iraj;Dezaki, Ebrahim Saedi
    • Parasites, Hosts and Diseases
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    • v.53 no.1
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    • pp.21-27
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    • 2015
  • Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were ${\alpha}$-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The $IC_{50}$ values for essential oil and methanolic extract was 8.4 and $28.9{\mu}g/ml$ against promastigotes, respectively. These values were 11.6 and $40.8{\mu}g/ml$ against amastigote forms, respectively. Glucantime as control drug also revealed $IC_{50}$ values of 88.3 and $44.6{\mu}g/ml$ for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.