The induction of chromosome aberrations in Hordeum vulgare germs after irradiation is studied for the dose range of 10 to 1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose is shown to be non -linear and has a dose-independent plateau within the range of 56-467 mGy where the level of cytogenetic damage is statistically significantly distinguished from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexities, using the most common quantitative criteria, demonstrates the benefit of the piecewise linear model over the linear and polynomial ones in approximating the cytogenetical disturbance frequency. The results of our study support the conclusion about indirect mechanism of chromosome aberrations induced by low doses or dose rates mutagenesis.
Schmitz-Feuerhake, Inge;Busby, Christopher;Pflugbeil, Sebastian
Environmental Analysis Health and Toxicology
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v.31
/
pp.1.1-1.13
/
2016
Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.
The treatment of tumors along curved surfaces with stationary electron beams using cone collimation may lead to non-uniform dose distributions due to a varying air gap between the cone surface and patient. For large tumors, more than one port may have to be used in irradiation of the chest wall, often leading to regions of high or low dose at the junction of the adjacent ports. Electron-beam arc therapy may elimination many of these fixed port problems. When treating breast tumors with electrons, the energy of the internal mammary port is usually higher than that of the chest wall port. Bolus is used to increase the skin dose or limit the range of the electrons. We invertiaged the effect of various arc beam parameters in the isodose distributions, and combined into a single arc port for adjacent fixed ports of different electron beam eneries. The higher fixed port energy would be used as the arc beam energy while the beam penetration in the lower energy region would be controlled by a proper thickness of bolus. We obtained the results of following: 1. It is more uniform dose distribution of electron to use rotation than stationary irradiation. 2. Increasing isocenter depth on arc irradiation, increased depth of maximum dose, reduction in surface dose and an increasing penetration of the linear portion of the curve. 3. The deeper penetration of the depth dose curve and higher X-ray background for the smaller field sized. 4. If the isocenter depth increase, the field effect is small. 5. The decreasing arc beam penetration with decreasing isocenter depth and the isocenter depth effect appears at a greater depth as the energy increases. 6. The addition of bolus produces a shift in the penetration that is the same for all depths leaving the shape of the curves unchanged. 7. Lead strips 5 mm thick were placed at both ends of the arc to produce a rapid dose drop-off.
Radiation side effects and complications on the ocular adnexa during electron beam therapy for orbital lymphoma can increase the incidence of posterior subcapsular cataracts. This study simulated a medical linear accelerator and a mathematical model of the eye using monte carlo simulations to evaluate the dose to the ocular adnexa and compare the shielding effectiveness on different parts of the ocular adnexa based on lens shield thickness. The dose assessment results of the ocular adnexa showed that the lens's sensitive area had the highest absorbed dose distribution when no shield was used, followed by the lens's non-sensitive area, the anterior chamber, vitreous humor, cornea, and eyelid in descending order. With the use of a shield, a 2 mm thick shield demonstrated a dose reduction effect of over 90% in the lens's sensitive area, over 83% in the non-sensitive area and anterior chamber, and a dose reduction effect of 30 to 62% in the vitreous body, cornea, and eyelid. For dose reduction in the lens's sensitive area during electron beam therapy for orbital lymphoma, it is necessary to use a shield of at least 2 mm thickness. Additionally, shielding strategies considering the thickness and area of the shield for other ocular adnexa besides the lens are required.
This study was conducted to quantitatively evaluate the recovery effects of herbal medicines on acetaminophen-induced hepatotoxicity. In the present study, the recovery effects of 251 herbal medicines on THLE-2 cells that had been damaged by acetaminophen were evaluated using an MTS assay. THLE-2 cells were cultured in 96-well plates and then pretreated with or without 60 ${\mu}M$ acetaminophen (${IC}_{50}$ value: 35.84) for 1 hr. Next, different herbal medicines were added to the wells, after which the cells were reincubated at $37^{\circ}C$ for 24 hr. After first round of screening, the candidate herbal medicines were selected based on a recovery rate of greater than 40% and their efficacy were then determined by dose response kinetic analysis. Among these extracts, 8 herbal medicines (Terminalia chebula, Pueraria lobata, Acronychia laurifolia, Lopatherum gracile, Oroxylum indicum, Cynanchum atratum, Senecio scandens, and Sophora flavescens) had a strong recovery effect on acetaminophen-induced damage in THLE-2 cells. Dose response non-linear regression analysis demonstrated that Senecio scandens showed the best recovery rate (98%), and that its ${EC}_{50}$ was 19.54 ng/mL. Additional studies of these herbal medicines should be conducted to determine if they possess novel therapeutic agents for the prevention or treatment of liver disorders.
Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.
Cho Heung Lae;Joo Young Don;Sohn Seung Chang;Sohn Chang Hak
Radiation Oncology Journal
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v.16
no.3
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pp.283-289
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1998
Purpose : This study was performed to analyze the efficacy of induction chemotherapy fellowed by radiation therapy in locally advanced non-small cell lung cancer Materials and Methods : Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine Patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. Results : Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). Conclusion : In stage III non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.
In case of radiation treatment using small field high-energy photon beams, an accurate dosimetry is a challenging task because of dosimetrically unfavorable phenomena such as dramatic changes of the dose at the field boundaries, dis-equilibrium of the electrons, and non-uniformity between the detector and the phantom materials. In this study, the absorbed dose in the phantom was measured by using an ion chamber and a diode detector widely used in clinics. $GAFCHROMIC^{(R)}$ EBT films composed of water equivalent materials was also evaluated as a small field detector and compared with ionchamber and diode detectors. The output factors at 10 cm depth of a solid phantom located 100 cm from the 6 MV linear accelerator (Varian, 6 EX) source were measured for 6 field sizes ($5{\times}5\;cm^2$, $2{\times}2\;cm^2$, $1.5{\times}1.5\;cm^2$, $1{\times}1\;cm^2$, $0.7{\times}0.7\;cm^2$ and $0.5{\times}0.5\;cm^2$). As a result, from $5{\times}5\;cm^2$ to $1.5{\times}1.5\;cm^2$ field sizes, absorbed doses from three detectors were accurately identified within 1%. Wheres, the ion chamber underestimated dose compared to other detectors in the field sizes less than $1{\times}1\;cm^2$. In order to correct the observed underestimation, a convolution method was employed to eliminate the volume averaging effect of an ion chamber. Finally, in $1{\times}1\;cm^2$ field the absorbed dose with a diode detector was about 3% higher than that with the EBT film while the dose with the ion chamber after volume correction was 1% lower. For $0.5{\times}0.5\;cm^2$ field, the dose with the diode detector was 1% larger than that with the EBT film while dose with volume corrected ionization chamber was 7% lower. In conclusion, the possibility of $GAFCHROMIC^{(R)}$ EBT film as an small field dosimeter was tested and further investigation will be proceed using Monte Calro simulation.
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.
Injectable chitosan hydrogels have attracted great potential due to sustained-release property and safety. Here, palmityl-acylated glycol chitosan (Pal-GC) was used to generate physically cross-linked hydrogels by virtue of hydrophobic attraction of linear fatty carbons. Glycol chitosan was chemically modified with N-hydroxysuccinimide-activated palmitic acid in dimethylsulfoxide (DMSO) containing dimethylaminopyridine. Through a series of preparation steps of (i) dialysis with DMSO, (ii) addition of palmityl-acylated exendin-4 (Ex4-C16), and (iii) dialysis with water, Pal-GC was self-assembled to form physically cross-linked hydrogels entrapped with Ex4-C16. The Pal-GC derivative was analyzed by using 1H NMR, and the surface morphology of Pal-GC hydrogels formed was examined by scanning electron microscopy. Also, the hypoglycemic effect induced by Pal-GC hydrogels containing Ex4-C16 (250 nmol/kg) was evaluated in non-fasted type 2 diabetic db/db mice and compared with GC hydrogels containing native Ex4 at the same dose. Results showed that palmityl group was successfully conjugated with the amines of glycol chitosan, and that Pal-GC efficiently generated the hydrogels formation. Moreover, Pal-GC hydrogels containing Ex4-C16 was found to greatly prolong the hypoglycemia duration (~ 4 days). This was due to the dual-functions of the palmityl groups present in both GC and exendin-4 such as hydrophobic attraction and plasma albumin-binding. We consider this new type of self-assembled GC hydrogels loaded with Ex4-C16 would be a promising long-acting sustained-release system with anti-diabetic property.
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