• Title/Summary/Keyword: dose-effect relationship

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Radiation Exposure and Cancer Mortality Among Nuclear Power Plant Workers: a Meta-analysis (원전종사자의 방사선 노출과 암사망 위험도와의 관련성에 대한 메타분석)

  • Park, Eun-Sook;Moon, Ki-Eun;Kim, Han-Na;Lee, Won-Jin;Jin, Young-Woo
    • Journal of Preventive Medicine and Public Health
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    • v.43 no.2
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    • pp.185-192
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    • 2010
  • Objectives: We conducted a meta-analysis to investigate the relationship between low external doses of ionizing radiation exposure and the risk of cancer mortality among nuclear power plant workers. Methods: We searched MEDLINE using key words related to low dose and cancer risk. The selected articles were restricted to those written in English from 1990 to January 2009. We excluded those studies with no fit to the selection criteria and we included the cited references in published articles to minimize publication bias. Through this process, a total of 11 epidemiologic studies were finally included. A publication bias was tested for using Egger's test. The homogeneity test was performed before the integration of each of the standardized mortality ratios (SMRs) and the result proved that the studies were heterogeneous. Results: We found significant decreased deaths from all cancers (SMR = 0.75, 95% CI = 0.62 - 0.90), all cancers excluding leukemia, solid cancer, mouth and pharynx, esophagus, stomach, rectum, liver and gallbladder, pancreas, lung, prostate, lymphopoietic and hematopoitic cancer. The findings of this meta-analysis were similar with those of the 15 Country Collaborative Study conducted by the International Agency for Research on Cancer. A publication bias was found only for liver and gallbladder cancer (p = 0.015). Heterogeneity was observed for all cancers, all cancers excluding leukemia, solid cancer, esophagus, colon and lung cancer. Conclusions: Our findings of low mortality for stomach, rectum, liver and gallbladder cancers may explained by the health worker effect. Yet further studies are needed to clarify the low SMR of cancers, for which there is no useful screening tool, in nuclear power plant workers.

Enhanced Local Anesthetic Efficacy of Bioadhesive Ropivacaine Gels

  • Cho, Cheong-Weon;Choi, Jun-Shik;Shin, Sang-Chul
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.357-363
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    • 2011
  • In relieving local pains, ropivacaine has been widely used. In case of their application such as ointments and creams, it is difficult to expect their effects for a significant period of time, because they are easily removed by wetting, movement and contacting. Therefore, the new formulations that have suitable bioadhesion were needed to enhance local anesthetic effects. The effect of drug concentration and temperature on drug release was studied from the prepared 1.5% Carboxymethyl cellulose (CMC) (150MC) gels using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. As the drug concentration and temperature increased, the drug release increased. A linear relationship was observed between the logarithm of the permeability coefficient and the reciprocal temperature. The activation energy of drug permeation was 3.16 kcal/mol for a 1.5% loading dose. To increase the skin permeation of ropivacaine from CMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the ropivacaine-CMC gels. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. For the efficacy study, the anesthetic action of the formulated ropivacaine gel containing an enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. According to the rat tail-flick test, 1.5% drug gels containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed the best prolonged local analgesic effects. In conclusion, the enhanced local anesthetic gels containing penetration enhancer and vasoconstrictor could be developed using the bioadhesive polymer.

Growth Responses of seven Intestinal Bacteria Against Phellodendron amurense Root-Derived Materials

  • Kim, Min-Jeong;Lee, Sang-Hyun;Cho, Jang-Hee;Kim, Moo-Key;Lee, Hoi-Seon
    • Journal of Microbiology and Biotechnology
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    • v.13 no.4
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    • pp.522-528
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    • 2003
  • The growth responses of Phellodendron amurense root-derived materials against seven intestinal bacteria were examined, using an impregnated paper disk agar diffusion method and spectrometric method under $O_2$-free condition. The biologically active constituent of the P. amurense root extract was characterized as berberine chloride ($C_{20}H_{18}NO_{41}Cl$) using various spectroscopic analyses. The growth responses varied depending on the bacterial strain, chemicals, and dose tested. At 1 mg/disk, berberine chloride strongly inhibited the growth of Clostridium perfringens, and moderately inhibited the growth of Escherichia coli and Streptococcus mutans without any adverse effects on the growth of three lactic acid-bacteria (Bifidobacterium bifidum, B. longum, and Lactobacillus acidophilus). The structure-activity relationship revealed that berberine chloride exhibited more growth-inhibiting activity against C. perfringens, E. coli, and S. mutans than berberine iodide and berberine sulfate. These results, therefore, indicate that the growth-inhibiting activity of the three berberines was much more pronounced as chloridated analogue than iodided and sulphated analogues. As for the morphological effect caused by 1 mg/disk of berberine chloride, most strains of C. perfringens were damaged and killed, indicating that berberine chloride showed a strong inhibition against C. perfringens. As naturally occurring growth-inhibiting agents, the P. amurense root-derived materials described could be useful as a preventive agent against diseases caused by harmful intestinal bacteria such as clostridia.

Ferritin Overload Suppresses Male Fertility Via altered Acrosome Reaction

  • Kwon, Woo-Sung;Rahman, Md Saidur;Kim, Ye-Ji;Ryu, Do-Yeol;Kahtun, Amena;Pang, Myung-Geol
    • Reproductive and Developmental Biology
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    • v.39 no.4
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    • pp.117-125
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    • 2015
  • Iron is required for cell viability but is toxic in excess. While the iron-mediated malfunction of testicular cells is well appreciated, the underlying mechanism(s) of this effect and its relationship with fertility are poorly understood. Ferritin is a ubiquitous intracellular protein that controls iron storage, ferroxidase activity, immune response, and stress response in cells. Ferritin light chain protein (FTL) is the light subunit of the Ferritin. Previously, we had identified the FTL in bovine spermatozoa following capacitation. In present study, to investigate the role of Ferritin in sperm function, mice spermatozoa were incubated with multiple doses (1, 10 and $100{\mu}M$) of sodium nitroprusside (SNP), an iron donor. SNP was increased Ferritin levels in a dose-dependent manner. The Ferritin was detected on the acrosome in spermatozoa by immunocytochemistry. Short-term exposure of spermatozoa to SNP increased tyrosine phosphorylation and the acrosome reaction (AR). Finally, SNP affected a significant decrease in the rate of fertilization as well as blastocyst formation during early embryonic development. On the basis of these results, we propose that the effects of Ferritin on the AR may reduce overall sperm function leads to poor fertility in males and compromised embryonic development.

A Study on the Efficient Use of Fused Phosphate for the Improvement of Upland Soil Productivity (토양(土壤)의 생산력증진을 위(爲)한 용성인비(鎔成燐肥)의 효과적인 시용법에(施用法) 관(關)하여)

  • Oh, Wang Keon;Han, Dong Uk;Lee, Jung Jai
    • Korean Journal of Soil Science and Fertilizer
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    • v.5 no.2
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    • pp.53-57
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    • 1972
  • In order to obtain some informations on the improvement of fertility of poor red yellow soils widely distributed in hilly lands of Korean peninsula, a pot culture study was made with a hill land soil in comparison with a fertile soil commonly used for vegetables. The results are as follows; 1. In addition to the normal application of phosphate, the mixing of a large dose of fused phosphate with whole soil increased the yeild of chinese cabbage remarkably, having the promotion particulary of the available phosphate level in the acidic low fertility soil. At the sometime the mixing seemed to short down the period of soil maturing to fertile for good crop. It is, however, considered that such effect of fused phosphate must also be evaluated economically through a long term experiment. 2. A relatively close relationship between the soil phosphate soluble in dilute acid and chinese cabbage growth was observed.

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Study on Validity of Using Injinho-tang in Non Alcohoic Fatty Liver Disease (비알콜성 지방간의 약물개발 중 인진호탕(茵蔯蒿湯)의 타당성 연구)

  • Ko, Heung;Kim, Ki Tae;Shin, Seon Mi
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.823-833
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    • 2012
  • Now a days, number of non alcoholic fatty liver patients are increasing more rapidly compare to past rate, and the average age of patients is getting younger, but there are no appropriate therapeutics in non alcoholic fatty liver disease. This study was aimed to analyze relationship between non alcoholic fatty liver disease and Injinho-tang. The papers were collected and analysed from domestic and international journals. The effects of Injinho-tang and constituent-herb were researched. Non-alcoholic fatty liver disease was induced complex causes of the metabolic syndrome. Medications that can be used in non-alcoholic fatty liver disease, it should be have many effects such as anti-hepatic fibrosis, hepatocyte protection, liver cancer inhibitory effect, inflammatory cytokine regulation, improving hyperlipidemia, weight control, decrease the toxicity of the drug, antioxidant. Injinho-tang (Artemisia capillaris Thunb, Gardenia fructus, Rhei rhizome) has been widely used in disease that causes jaundice and liver biliary disease. Drugs for standardization of Injinho-tang index components(6,7-Dimethylesculetin, geniposide, rhein) have been presented. And Injinho-tang has been proven reliability in the administration of single dose toxicity. Also clinical stability in the administration of four years was reported. Injinho-tang has been reported some effects which anti-hepatic fibrosis, hepatocyte protection, liver cancer inhibitor, inflammatory cytokine regulation, improving hyperlipidemia, weight control, decrease the toxicity of the drug, and antioxidant. Therefore, Injinho-tang can be used in Non alcoholic fatty liver disease without Syndrome Differentiation.

Inhibitory Effect of Methanolic Extract from Radix Trichosanthis on Melanin Synthesis (천화분 메탄올 추출물의 멜라닌 형성 억제 효과)

  • 김정근;김남권;임규상;김진;성병곤
    • The Journal of Korean Medicine
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    • v.23 no.4
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    • pp.45-54
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    • 2002
  • Objectives: In order to investigate the relationship of Radix Trichosanthis components and the melanin synthesis, the author has analyzed the cell viability and tyrosinase activity, melanin content and morphologic changes in n-hexane, EtOAc, n-BuOH, and H2O fraction. Methods: At first, in order to determine the concentration of the Radix Trichosanthis component, the author investigated the viability of B16 melanoma cell. To measure the effects of Trichosanthes kirilowii extracts (n-BuOH, n-Hexane, EtOAc, H2O fractions) on the viability of A549 cells, A549 cells were treated with various concentrations (from 0.5 to $25{\;}\mu\textrm{g}/ml$) of components of Trichosanthes kirilowii. After 24hrs, the cell viability was measured by MTT assay. The EtOAc components of Trichosanthes kirilowii decreased the viability of A549 cells in a dose-dependent manner. H2O and n-BuOH components had no cell toxicity till $25{\;}\mu\textrm{g}/ml$, the n-hexane component showed minor cell toxicity at $25{\;}\mu\textrm{g}/ml$ and the EtOAc component cell toxicity was revealed at $5{\;}\mu\textrm{g}/ml$ concentration. Results: 1. The results of tyrosinase activity and the Radix Trichosanthis component; n-hexane and EtOAc components controlled it effectively; the n-BuOH components were less effective. 2. The results of melanin content analysis showed that the n-hexane and EtOAc components effectively inhibited, the n-BuOH fraction inhibited less, and H2O component didn't inhibit the terminal melanin formation. 3. In the n-BuOH and H2O component there were no changes, but in the n-hexane component the melanin content was effectively inhibited. 4. In the EtOAc fraction, although the melanin content was inhibited, the cell count was evidently suppressed, Of all of the Radix Trichosanthis components, the n-Hexane and EtOAc fractions inhibited the melanin synthesis best, but owing to its toxicity, the EtOAc components inhibited the cell count. Conclusion: The above results demonstrated that Radix Trichosanthis n-hexane fraction efficiently inhibited the tyrosinase activity and melanin synthesis.

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Apoptosis-inducing effect and structural basis of Polygonatum cyrtonema lectin and chemical modification properties on its mannose-binding sites

  • Liu, Bo;Xu, Xiao-Chao;Cheng, Yan;Huang, Jian;Liu, Yan-Hong;Liu, Zhen;Min, Ming-Wei;Bian, He-Jiao;Che, Jing;Bao, Jin-Ku
    • BMB Reports
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    • v.41 no.5
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    • pp.369-375
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    • 2008
  • Polygonatum cyrtonema Lectin (PCL), which is classified as a monocot mannose-binding lectin, has received great regards for its uniquely biological activities and potentially medical applications in cancer cells. This paper was initially aimed to study apoptosis of PCL on Hela cells. Thus, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was carried out. Through observation of cell morphologic changes and Lactate dehydrogenase (LDH) activity-based cytotoxicity assays, PCL induced HeLa cell apoptosis in a dose-dependent manner. To further gain structural basis, multiple alignments, homology modeling and docking experiments were performed to analyze the correlation between its biological activities and mannose-binding sites. Eventually, considering docking data, chemical modification properties on the three mannose-binding sites were analyzed by a series of biological experiments (e.g., hemagglutinating and mitogenic activity assays, fluorescence and Circular Dichrosim (CD) spectroscopy) to profoundly identify the role of some key amino acids in the structure-function relationship of PCL.

Functional characterization of $P_{2X}/P_{2Y}$ receptor in isolated swine renal artery

  • Kim, Joo-heon;Jeon, Je-cheol;Lee, Sang-kil;Lee, Su-jin;Lee, Younggeon;Won, Jinyoung;Kang, Jae seon;Hong, Yonggeun
    • Korean Journal of Veterinary Research
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    • v.47 no.4
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    • pp.371-378
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    • 2007
  • To understand the role of $PM_{2X}/P_{2Y}$ receptor in cortex region of kidney and renal artery, molecular and functional analysis of $PM_{2X}/P_{2Y}$ receptor by pharmacophysiological skill in conventional swine tissues were performed. In functional analysis of $P_{2Y}$ receptor for vascular relaxation, 2-methylthio adenosine triphosphate, a strong agonist of $P_{2Y}$ receptor, induced relaxation of noradrenaline (NA)-precontracted renal artery in a dose-dependent manner. Strikingly, relaxative effect of ATP, 2-msATP, agonists of $P_{2Y}$ receptor, abolished by treatment of reactive blue 2, a putative $P_{2Y}$ receptor antagonist. In contrast, no significant differences of gene encoding $PM_{2X}/P_{2Y}$ and protein expression in immortalized suprachiasmatic nucleus from brain, primary isolated vascular smooth muscle cells from renal artery of pigs and HEK293 from human embryonic kidney under with/without adenosine triphosphate were observed. Taken together, the relationship between molecular and functional characteristic of $PM_{2X}/P_{2Y}$ receptors in conventional pig should be considered that they are another important factor which regulate the kidney function in swine. Based on this study, we propose the purinergic receptor as well as adrenergic and cholinergic receptors is an essential component of the renal homeostasis.

Pharmacokinetic Characteristics of Levosulpiride in Relation to the Genetic Polymorphism of MDR1: From Knockout Mouse to Human

  • Cho, Hea-Young;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.37 no.5
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    • pp.297-303
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    • 2007
  • The purposes of this study were to clarify the involvement of P-glycoprotein (P-gp) in the efflux of levosulpiride in knockout mice that lack the mdr1a1b gene and to evaluate the relationship between the genetic polymorphisms in MDR1 gene (exon 21) and levosulpiride disposition in healthy Korean subjects. After oral administration ($10\;{\mu}g/g$) of levosulpiride to mdr1a/1b(-/-) and wild-type mice, plasma and brain samples were obtained at 45 min. We also investigated the genotype for MDR1 (exon 21) gene in humans using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A single oral dose of 25 mg levosulpiride was administered to 58 healthy subjects, who were based on the MDR1 genotype for the G2677T SNP. Blood samples were taken up to 36 hr after dosing. The concentrations of levosulpiride in mouse plasma and brain were statistically significant difference between the two animal groups (P<0.05). In addition, the average brain-to-plasma concentration ratio (Kp) of levosulpiride was 3.4-fold (P<0.01) higher in the mdr1a/1b(-/-) mice compared with the wild-type mice. We also found that the values of $AUC_{0-{\infty}$, partial AUC ($AUC_{0-4h}$) and $C_{max}$ were significantly different between homozygous 2677TT subjects and the subjects with at least one wild-type allele (GG and GT subjects, P=0.012 for $AUC_{0-{\infty}$; P=0.008 for $AUC_{0-4h}$; P=0.038 for $C_{max}$). The results confirm that levosulpiride is a P-gp substrate in vivo, and clearly demonstrate the effect of SNP 2677G>T in exon 21 of the MDR1 gene on levosulpiride disposition.