• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.99-116
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• 2016

We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.275-286
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• 2001

Purpose : To setup procedures of quality assurance (OA) for implementing intensity modulated radiation therapy (IMRT) clinically, report OA procedures peformed for one patient with prostate cancer. Materials and methods : $P^3IMRT$ (ADAC) and linear accelerator (Siemens) with multileaf collimator are used to implement IMRT. At first, the positional accuracy, reproducibility of MLC, and leaf transmission factor were evaluated. RTP commissioning was peformed again to consider small field effect. After RTP recommissioning, a test plan of a C-shaped PTV was made using 9 intensity modulated beams, and the calculated isocenter dose was compared with the measured one in solid water phantom. As a patient-specific IMRT QA, one patient with prostate cancer was planned using 6 beams of total 74 segmented fields. The same beams were used to recalculate dose in a solid water phantom. Dose of these beams were measured with a 0.015 cc micro-ionization chamber, a diode detector, films, and an array detector and compared with calculated one. Results : The positioning accuracy of MLC was about 1 mm, and the reproducibility was around 0.5 mm. For leaf transmission factor for 10 MV photon beams, interleaf leakage was measured $1.9\%$ and midleaf leakage $0.9\%$ relative to $10\times\;cm^2$ open filed. Penumbra measured with film, diode detector, microionization chamber, and conventional 0.125 cc chamber showed that $80\~20\%$ penumbra width measured with a 0.125 cc chamber was 2 mm larger than that of film, which means a 0.125 cc ionization chamber was unacceptable for measuring small field such like 0.5 cm beamlet. After RTP recommissioning, the discrepancy between the measured and calculated dose profile for a small field of $1\times1\;cm^2$ size was less than $2\%$. The isocenter dose of the test plan of C-shaped PTV was measured two times with micro-ionization chamber in solid phantom showed that the errors upto $12\%$ for individual beam, but total dose delivered were agreed with the calculated within $2\%$. The transverse dose distribution measured with EC-L film was agreed with the calculated one in general. The isocenter dose for the patient measured in solid phantom was agreed within $1.5\%$. On-axis dose profiles of each individual beam at the position of the central leaf measured with film and array detector were found that at out-of-the-field region, the calculated dose underestimates about $2\%$, at inside-the-field the measured one was agreed within $3\%$, except some position. Conclusion : It is necessary more tight quality control of MLC for IMRT relative to conventional large field treatment and to develop QA procedures to check intensity pattern more efficiently. At the conclusion, we did setup an appropriate QA procedures for IMRT by a series of verifications including the measurement of absolute dose at the isocenter with a micro-ionization chamber, film dosimetry for verifying intensity pattern, and another measurement with an array detector for comparing off-axis dose profile.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.149-155
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• 2006

Meningeal hemangiopericytoma (HPC) is an uncommon dura-based tumor and can recur not only locally but also distantly in the neural axis or extraneural sites. We report our experience of radiation therapy, one preoperative and one elective postoperative, In two patients with meningeal HPC and reviewed the role of radiation therapy. A 41-year-old man (Case 1) presented with a 3-month history of headache and right hemiparesis. The mass was nearly unresectable at the first and second operation and diagnosed as meningeal HPC. Preoperative radiation therapy was given with a total dose of 55.8 Gy/31 fractions to the large residual mass of left frontoparietal area. Follow-up computerized tomography (CT) showed marked regression of tumor after radiation therapy. The third operation was peformed to remove the residual tumor at 6 months after the radiation therapy and a $2{\times}2cm$ sized tumor was encountered. The mass was totally removed. The serial follow-up CT showed no evidence of recurrence and he is alive without distant metastasis for 4 years and 10 months after the first operation. A 45-year-old woman (Case 2) presented with suddenly developed headache and visual impairment. Tumor mass occupying right frontal lobe was removed with the preoperative diagnosis of meningioma. It was totally removed with attached sagittal sinus and diagnosed as meningeal HPC. Elective postoperative radiation therapy was peformed to reduce local recurrence with a total dose of 54 Gy/30 fractions to the involved area of right frontal lobe. She is alive for 5 years maintaining normal activity without local recurrence and distant metastasis.

• Journal of the Korean Society of Radiology
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• v.11 no.2
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• pp.79-85
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• 2017

The purpose of this study is to investigate the cause analysis according to the difference between the pre exposure tube voltage and actual exposure tube voltage in mammography in connection with breast pressure thickness, breast size and body mass index and to find the improvement. The study tracked 377 women age 40 and older among the mammography examiners conducted by the National Health Insurance Corporation. It was analyzed that breast pressure thickness, breast size and body mass index according to the difference between the pre exposure tube voltage and actual exposure tube voltage among the parameters of dose report been sent to the picture archiving communication system with reference to the image with cranio-caudal projection in mammography. As are result, it shows that the thicker the breast thickness, smaller the breast size and lower body mass index, the higher the difference of tube voltage. In conclusion, the minimum tube voltage of mammography machine should be reset in order to set the tube voltage according to breast pressure thickness and breast size that are suitable for our country in mammography, in addition, it was considered that radiologist should make an effort to reduce radiation exposure and make a good quality image with reducing the difference of mammography condition by making a correct exposure condition in case of examining the patients with thin breast pressure and small breast size.

• Radiation Oncology Journal
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• v.28 no.1
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• pp.50-56
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• 2010

Purpose: We report the results of an external audit on the absorbed dose of radiotherapy beams independently performed by third parties. For this effort, we developed a method to measure the absorbed dose to water in an easy and convenient setup of solid water phantom. Materials and Methods: In 2008, 12 radiotherapy centers voluntarily participated in the external auditing program and 47 beams of X-ray and electron were independently calibrated by the third party’s American Association of Physicists in Medicine (AAPM) task group (TG)-51 protocol. Even though the AAPM TG-51 protocol recommended the use of water, water as a phantom has a few disadvantages, especially in a busy clinic. Instead, we used solid water phantom due to its reproducibility and convenience in terms of setup and transport. Dose conversion factors between solid water and water were determined for photon and electron beams of various energies by using a scaling method and experimental measurements. Results: Most of the beams (74%) were within ${\pm}2%$ of the deviation from the third party's protocol. However, two of 20 X-ray beams and three of 27 electron beams were out of the tolerance (${\pm}3%$), including two beams with a >10% deviation. X-ray beams of higher than 6 MV had no conversion factors, while a 6 MV absorbed dose to a solid water phantom was 0.4% less than the dose to water. The electron dose conversion factors between the solid water phantom and water were determined: The higher the electron energy, the less is the conversion factor. The total uncertainty of the TG-51 protocol measurement using a solid water phantom was determined to be ${\pm}1.5%$. Conclusion: The developed method was successfully applied for the external auditing program, which could be evolved into a credential program of multi-institutional clinical trials. This dosimetry saved time for measuring doses as well as decreased the uncertainty of measurement possibly resulting from the reference setup in water.

• Progress in Medical Physics
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• v.17 no.4
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• pp.232-237
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• 2006

The aim of this study was to develop the calculation algorithm of source strength of Ir-192 source In terms of the absorbed dose to water instead of an apparent activity (Ci). For this work the Multi Purpose Brachytherapy Phantom(MPBP) was developed, which was designed to locate the source and the chamber precisely at a specific position Inside the water phantom. The reference point of measurement was set at the 5 cm distance along the transverse axis of the source. For a brachytherapy source calibration, the absorbed dose to water calibration factor ($N_{D.W.Q}$) of an lonization chamber were determined and then apply standard protocols of absorbed dose to water. The calibration factor ($N_{D.W.Q}$) of the ion chamber (TM30013, PTW, Germany) was determined using the EGSnrcCPP Monte Carlo Code. The calculated calibration factor ($N_{D.W.Q}$) was 5.28 cGy/nC. The calculated factor was then used to determine the absorbed dose to water from which the air kerma strength for an Ir-192 source can be easily derived at the reference point (5 cm). The calculated air kerma strength showed discrepancies of -0.6% to +1.8% relative to the air kerma strength provided by the vendor, In this work we demonstrated that the air kerma strength ($S_k$) could be determined from the absorbed dose to water calibration factor for Ir-192 source. In audition, this source calibration method could be applied directly to the dose Calculation formalism of AAPM report TG-43.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.57-64
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• 1997

Purpose : Before we report the results of curative radiotherapy in cervix cancer patients, we review the significance and safety of our dose specification methods in the brachytherapy system to have the insight of the potential Predictive value of doses at specified points. Matersials and Methods : We analyze the 리5 cases of cervix cancer patients treated with intracavitary brachytherapy in the lateral simulation film we draw the isodose curve and observe the absorbed dose rate of point A, the reference point of bladder(SBD) and rectum(SRD). In the sagittal view of Pelvic MRI film we demarcate the tumor volume(TV) and determine whether the prescription dose curve of point A covers the tumor volume adequately by drawing the isodose curve as correctly as possible. Also we estimate the maximum Point dose of bladder(MBD) and rectum(MRD) and calculate the inclusion area where the absorbed dose rate is higher than that of point A in the bladder(HBV) and rectum(HRV), respectively. Results : Of forty-five cases, the isodose curve of point A seems to cover tumor volume optimally in only 24(53%). The optimal tumor coverage seems to be associated not with the stage of the disease but with the tumor volume. There is no statistically significant association between SBD/SRD and MBD/MRD, respectively. SRD has statistically marginally significant association with HRV, while TV has statistically significant association with HBV and HRV. Conclusion : Our current treatment calculation methods seem to have the defect in the aspects of the nonoptimal coverage of the bulky tumor and the inappropriate estimation of bladder dose. We therefore need to modify the applicator geometry to optimize the dose distribution at the position of lower tandem source. Also it appears that the position of the bladder in relation to the applicators needs to be defined individually to define 'hot spots'.

• Journal of Yeungnam Medical Science
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• v.20 no.1
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• pp.79-84
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• 2003

Pyoderma gangrenosum is uncommon neutrophilic dermatosis characterized by richness of the mature neutrophilic polynuclear dermal infiltrate. Pyoderma gangrenosum is associated with variable diseases, most commonly inflammatory bowel disease, hematological diseases, malignancies, but it is reported rarely in rheumatoid arthritis. We report a case of pyoderma gangrenosum in rheumoid arthritis patient. A 50-year-old woman admitted to our hospital due to painful pretibial ulcerative skin lesions. She had been treated as rheumatoid arthritis for 8 years. At admission, body temperature was $36.5^{\circ}C$ and other vital sign was unremarkable. Physical examination revealed right pretibial ulceration, multiple pustules on left pretibial area and both palms. Laboratory studies revealed WBC count 7,600/uL (neutrophils 60.3%, eosinophil 3.2%), hemoglobin 11.4 g/dL, platelet count 319,000/uL, ESR 65 mm/hour. Other lab findings were also unremarkable. Skin biopsy was done, which showed dense dermal infiltrate of neutrophils and wound culture were negative. By 8 weeks after systemic high dose corticosteroid (1 mg/kg/day), cyclosporine A (5 mg/kg/day), sulfasalazine 2 g therapy, symptoms and skin ulceration were being improved. Without skin relapse, she is followed up our hospital with low dose corticosteroid and sulfasalazine.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.83-90
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• 2015

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.902-905
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• 2002

The most common form of genetic nephrogenic diabetes insipidus(NDI), a rare inherited disorder, is congenital and is transmitted in an X-linked recessive mode. It is refractory to the antidiuretic effect of normal to moderately increased levels of plasma arginine vasopressin(AVP) but, in some cases, may respond to high levels of the hormone or its analogue, deamino-D-arginine vasopressin(DDAVP). X-linked congenital NDI has now been linked to over 128 different mutations in diverse coding regions of the AVP receptor 2(AVPR2) gene. The functional effects of these mutations vary from complete loss of responsiveness to a simple shift to the right in the dose response curve. We report a case of congenital partial NDI, with transversion of A to G at codon 280 of the AVPR2 gene, resulting in a subsequent change of amino acid from tyrosine to cysteine, and that has been effective with hydrochlorothiazide and high dose of DDAVP.