Objective : The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type : Glu, 'H' ; variant : Lys, 'h') and Glu308Gly(wild-type : Glu, 'D' ; variant : Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. Methods : Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. Results : A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. Conclusion : The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.
In this study, we assessed the effect of reduction of tumor volume in the head and neck cancer by using RANDO phantom in Static Intensity-Modulated Radiation Therapy (S-IMRT) and Volumetric-Modulated Arc Therapy (VMAT) planning. RANDO phantom's body and protruding volumes were delineated by using Contour menu of Eclipse™ (Varian Medical System, Inc., Version 15.6, USA) treatment planning system. Inner margins of 2 mm to 10 mm from protruding volumes of the reference were applied to generate the parameters of reduced volume. In addition, target volume and Organ at Risk (OAR) volumes were delineated. S-IMRT plan and VMAT plan were designed in reference. These plans were assigned in the reduced volumes and dose was calculated in reduced volumes using preset Monitor unit (MU). Dose Volume Histogram (DVH) was generated to evaluate treatment planning. Conformity Index (CI) and R2 in reference S-IMRT were 0.983 and 0.015, respectively. There was no significant relationship between CI and the reduced volume. Homogeneity Index (HI) and R2 were 0.092 and 0.960, respectively. The HI increased when volume reduced. In reference VMAT, CI and R2 were 0.992 and 0.259, respectively. There was no relationship between the volume reduction and CI. On the other hand, HI and R2 were 0.078 and 0.895, respectively. The value of HI increased when the volume reduced. There was significant difference (p<0.05) between parameters (Dmean and Dmax) of normal organs of S-IMRT and VMAT except brain stem. Volume reduction affected the CI, HI and OAR dose. In the future, additional studies are necessary to incorporate the reduction of the volume in the clinical setting.
The Journal of Korean Society for School & Community Health Education
/
v.18
no.1
/
pp.1-12
/
2017
Objectives: This study aimed to analyze sexual experience rates according to socio-demographic factors, health behavioral factors, and internet use time, and to identify sex experience related factors in high school students using the data from the 11th Korean Youth Health Risk Behavior Web-Based Survey. Methods: A total of 33,744 students (17,346 boys and 16,398 girls) in high schools were analyzed using the SPSS WIN version 22 program. SPSS complex samples methods were used for analyses. Socio-demographic factors, health behavioral factors, and internet use time as independents variables were included. The complex samples logistic regression analyses were used to calculate the odds ratio of the sexual experience according to the socio-demographic factors, health behavioral factors and internet use time. Unweighted frequencies and percentages were represented in result tables. Results: 3.6% of girls and 9.9% of boys in high school had sexual experiences. Daily average smoking amount and daily alcohol drinking amount were a dose-response relationship with sexual experience after considering confounding factors. Students who smoke 10-19 cigarettes had 5.74 times higher risk and 20 cigarettes or more had 7.27 times higher risk of sexual experiences, comparing with non-smoking students, relatively. Likewise, students who drink soju less than 1-2 bottles and more than 2 bottles had 3.82- and 4.35 times higher chance of sexual experiences, compared with non drinking students, respectively. Conclusions: We found that there were the dose-response relationship between health behavioral characteristics and sexual experiences. Further research is needed to identify an interaction effect between smoking and drinking alcohol on sexual experiences in high school students.
Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.
It is well known that the uterine contractility is affected by sexual hormone. In this experiment, the authors attempted to study the influences of testosterone and estrogen or the uterine contractility to oxytocics. The contractile sensitivity of the excised uterine muscle of non-castrated and castrated rabbits with testosterone and estrogen 24 hours before experiment is observed respectively. And the cholinesterase activity and electrolytes (Na, K, Ca and Mg) in the uterine muscle are measured in order to study the relationship with contractile sensitivity and those changes. The results obtained were summarized as follows: 1. The contractile effect of spareng on the excised uterine muscle of non-castrated rabbits pretreated with estrogen was markedly increased in small dose, but that of rabbits pretreated with testosterone was significantly increased in large dose, comparing with that of the control group. In castrated rabbits, the contractile sensitivity of the uterine muscle to spareng was significantly increased by pretreatment with estrogen in large dose but it was markedly decreased by pretreatment with testosterone in small dose. 2. The contractile effect of quinine on the excised uterine muscle of non-castrated rabbits pretreated with estrogen was significantly decreased but that of castrated rabbits pretreated with both estrogen and testosterone were markedly increased comparing with that of the control group. 3. The cholinesterase activity in the uterine muscle of non-castrated rabbits was significantly increased by pretreatment with small dose of estrogen or large dose of testosterone, but that of castrated rabbits was markedly decreased by pretreatment with large dose of estrogen. 4. Na and K contents in the uterine muscle of non-castrated rabbits were markedly increased by pretreatment with both estrogen and testosterone, but that of castrated rabbits was significantly increased by pretreatment with small dose of estrogen. 5. Ca content in uterine muscle of non-castrated rabbits was significantly decreased by pretreatment with both large dose of estrogen and testosterone but increased by pretreatment of testosterone. In castrated rabbits, Ca content was significantly decreased by pretreatment with both estrogen and testosterone. 6. Mg content in the uterine muscle of non-castrated rabbits was markedly increased by pretreatment with estrogen and small dose of testosterone, but that of castrated rabbits was significantly decreased by pretreatment with both large dose of estrogen and testosterone.
To determine if micronucleus (MN) assay could be used to predict the absorbed dose of victims after accidental radiation exposure, we carried out to assess the absorbed dose depending on the numerical changes of MN in human peripheral blood lymphocytes after $^{60}Co\;{\gamma}-rays$ exposure in the range of 0.25 to 1 Gy, respectively. The MNs were observed at very low doses, and the numerical changes according to doses. Satisfactory dose-effect calibration curve is observed after low dose irradiation of human lymphocytes in vitro. When plotting on a linear scale against radiation dose, the line of best fit was $Y=(0.02{\pm}0.0009)+(0.033{\pm}0.010)D+(0.012{\pm}0.012)D^2$. The dose-response curve for MN induction immediately after irradiation was linear-quadratic and has a significant relationship between the frequencies of MN and dose. These data show a trend towards increase of the numbers of MN with increasing dose. The number of MN in lymphocytes that were observed in the control group is $0.1610{\pm}0.0093/cell$. Accordingly, MN assay in human peripheral lymphocytes could be a useful in viva model for studying radio-protective drug sensitivity or screening test, microdosimertic indicator and radiation-induced target organ injury. Since MN assay is simple, rapid and reproducible, it will also be a biodosimetric indicator for individual dose assessment after accidental exposure.
Xin, Yue;Li, Xiao-Yu;Sun, Shi-Ran;Wang, Li-Xia;Huang, Tao
Asian Pacific Journal of Cancer Prevention
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v.16
no.12
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pp.5125-5135
/
2015
Background: Total fat intake may be associated with increased risk of breast cancer, and fish oil has been suggested as a protection factor to breast cancer. But the effect of vegetable oils is inconclusive. We aimed to investigate the association with high vegetable oils consumption and breast cancer risk, and evaluated their dose-response relationship. Design: We systematically searched the MEDLINE, EMBASE, Cochrane databases, and CNKI updated to December 2014, and identified all observational studies providing quantitative estimates between breast cancer risk and different vegetable oils consumption. Fixed or random effect models were used to estimate summary odds ratios for the highest vs. lowest intake, and dose-response relationship was assessed by restricted cubic spline model and generalized least-squares trend (GLST) model. Results: Five prospective cohort studies and 11 retrospective case-control studies, involving 11,161 breast cancer events from more than 150,000 females, met the inclusion criteria. Compared with the lowest vegetable oils consumption, higher intake didn't increased the risk of breast cancer with pooled OR of 0.88 (95% CIs:0.77-1.01), and the result from dose-response analyses didn't show a significant positive or negative trend on the breast cancer risk for each 10g vegetable oil/day increment (OR=0.98, 95% CIs: 0.95-1.01). In the subgroup analyses, the oils might impact on females with different strata of BMI. Higher olive oil intake showed a protective effect against breast cancer with OR of 0.74 (95% CIs: 0.60-0.92), which was not significant among the three cohort studies. Conclusions: This meta-analyses suggested that higher intake of vegetable oils is not associated with the higher risk of breast cancer. Olive oil might be a protective factor for the cancer occurrence among case-control studies and from the whole. Recall bias and imbalance in study location and vegetable oils subtypes shouldn't be ignored. More prospective cohort studies are required to confirm the interaction of the impact of vegetable oils on different population and various cancer characteristic, and further investigate the relationship between different subtype oils and breast cancer.
Ha, Mi-Na;Yoo, Keun-Young;Ha, Sung-Whan;Kim, Dong-Hyun;Cho, Soo-Hun
Journal of Preventive Medicine and Public Health
/
v.33
no.2
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pp.165-173
/
2000
Objectives : To assess the availability of the glycophorin A (GPA) assay to detect the biological effect of ionizing radiation in workers exposed to low-doses of radiation. Methods : Information on confounding factors, such as age and cigarette smoking was obtained on 144 nuclear power plant workers and 32 hospital workers, by a self-administered questionnaire. Information on physical exposure levels was obtained from the registries of radiation exposure monitoring and control at each facility. The GPA mutant assay was performed using the BR6 method with modification by using a FACScan flow cytometer. Results : As confounders, age and cigarette smoking habits showed increasing trends with GPA variants, but these were of no statistical significance. Hospital workers showed a higher frequency of the GPA variant than nuclear power plant workers in terms of the NO variant. Significant dose-response relationships were obtained from in simple and multiple linear regression models. The slope of the regression equation for nuclear power plant workers was much smaller than that of hospital workers. These findings suggest that there may be apparent dose-rate effects. Conclusion : In population exposed to chronic low-dose radiation, the GPA assay has a potential to be used as an effective biologic marker for assessing the bone marrow cumulative exposure dose.
Five hundred and fifty patients treated for carcinoma of the uterine cervix at the Department of Therapeutic Radiology, Seoul National University Hospital from 1979 to 1986, were analyzed retrospectively for late bladder complications. Of them,468 patients received primary radiotherapy for the cervix cancer in intact uterus, and the other 82 patients were treated postoperatively. The cumulative incidence of radiation induced bladder complication of grade 2 or 3 was $2.5\%$ at five years. The mean bladder dose for the group of patients with complication was higher than that of the group without complication, and the difference was statistically significant (p<0.01). But relationship between mean bladder dose and severity of complication was not found. The frequency of complication (grade I, II, III) increased as a function of radiation dose to bladder from $5.0\%$ for patients with bladder dose less than 6,500 cGy to $27.7\%$ for patients with bladder dose higher than 8,000 cGy. Among various factors, the age of patient and the distance between ovoids turned out to have significant effect on the complication.
To assess the effects of a proton beam on oyster mushrooms (Pleurotus ostreatus), the genetic diversity and phylogenetic relationships among strains induced by a proton beam were investigated based on a clustering analysis. According to an AFLP DNA polymorphism analysis, the induced strains were divided into four groups that coincided with the dose. When applying proton-beam radiation, the dissimilarity among the induced strains increased when increasing the dose. When using more than 400 Gy, the genetic dissimilarity of the irradiated strains was 46-58%. Thus, evaluating the induced strains using the AFLP technique was effective in revealing the mutation effect of the proton beam.
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