• Asian-Australasian Journal of Animal Sciences
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• v.14 no.2
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• pp.237-242
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• 2001

Colostrum deprived, newborn pigs (N=12, $1.64{\pm}0.05kg$) were used to study the renal threshold of carnitine, and effects of emulsified medium-chain triglyceride (MCT, tri-8:0) feeding on kinetics of plasma carnitine and urinary carnitine excretion. An arterial catheter was inserted through an umbilical artery, and a bladder catheter was inserted via the urachus. Piglets were oro-gastrically gavaged with one of six carnitine levels (0, 60, 120, 180, 240, $480{\mu}mol/kg\;W^{0.75}$) with (+MCT) or without medium-chain triglycerides (-MCT) in 0.9% NaCl solution. Blood was sampled into heparinized tubes at 0, 1, 2, 4, 6, 8, 14, and 20 h after gavage, and urine was collected and pooled into 1 h or 2 h composite samples to determine free- and short-chain carnitine concentrations. Plasma from the 12 newborn piglets before gavage contained $10.6{\pm}1.2{\mu}mol/L$ free carnitine and $7.2{\pm}0.6{\mu}mol/L$ acid-soluble acyl carnitine. The renal threshold for carnitine was similar between the MCT and the +MCT group (42.6 13.1 and $46.4{\pm}2.0{\mu}mol/L$, respectively), but the correlation between plasma free carnitine and urinary excretion was altered. Plasma free carnitine linearly increased with increasing carnitine dosage (-MCT group, $R^2=0.95$, p<0.001; +MCT group, $R^2=0.91$, p<0.001), but was decreased by 50% when medium-chain triglycerides were fed. The peak in plasma free carnitine concentration was depressed by medium-chain triglycerides feeding also. Therefore, the plasma and urinary short-chain/free carnitine ratio of the +MCT group was increased by 100% and 40%, respectively (p<0.01). Feeding of medium-chain triglycerides may delay plasma carnitine elevation via altering the kinetics of absorption. Similarly, the plasma and urinary short-chain/free carnitine ratio were affected by interaction between medium-chain triglycerides and time (p<0.01). The present study suggests that an oral carnitine dose over $480{\mu}mol/kg\;W^{0.75}$ may be needed to reach the free carnitine renal threshold within a short period, especially when provided together with medium-chain triglyceride.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.9
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• pp.1330-1335
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• 2005

Red brownish p-pheylenediamine (PPD) has been widely used hair dye for women. The dye was known to cause systemic anaphylaxis, dermatitis and bladder cancer. But the effect of PPD toxicity with oxygen free radical has not been studied. This study investigated the degree of skin injury by PPD. PPD ($2.5\%$ PPD in $2\%\;NH_{4}OH$) was applied to the rat skin ($25 mg/16.5\;cm^2$) 3 or 5 times every other day. Histopathological findings demonstrated the proliferation of epithelial cells and the increased keratinization by PPD. The activities of glucose 6-phosphatase (G6Pase) was decreased and acid phosphatase (ACP) was increased in PPD-applied rat skin. Groups in which PPD was applied 5 times were more damaged than groups applied 3 times. To examine the relationship between tissue damage and oxygen free radicals, effect of PPD on xanthine oxidase (XO) activity was measured and XO activity was more significantly increased in the group treated with PPD 5 times than 3 times. However, reduced glutathione (GSH) content, and the activities of catalase (CAT), super-oxide dismutase (SOD) and glutathione S -transferase (GST) were more decreased in PPD-applied groups than in controls. Even though the activities of XOD was not changed in the group treated with PPD 3 times, the decreased activities of oxygen free radical system and the damaged skin tissue were observed. This result might be caused by the production of toxic PPD metabolites in rat skin. In conclusion, topical PPD application led to skin injury in a dose-dependent manner, probably due to the generation rate of oxygen free radical.

• The Korean Journal of Nuclear Medicine
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• v.23 no.2
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• pp.219-223
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• 1989

Inflammation scan using radiolabelled leukocytes has high sensitivity and specificity. Several methods for labelling leukocytes have been evaluated using P-32 diisopropyl fluorophosphate (DFP-32), H-3 thymidine, Cr-51 chromate, Ga-67 citrate and Tc-99m-sulfur colloid. In-111-oxine has proved so far to be the most reliable agent for labelling leukocytes. In-111-oxine is, however, expensive, not easily available when needed, and its radiation dose to leukocytes is relatively high. Moreover, resolution of the resultant image is relatively poor. Tc-99m is still the agent of choice because of, as compared with the indium, its favorable physical characteristics, lower cost and availability. Now the technique for labelling the leukocytes with technetium is successfully obtained using the lipophilic HAPAO with higher efficiency for granulocytes than for other cells. With this technique it is possible to label leukocytes in plasma to improve the viability of the leukocytes. Inflammation scan using Tc-99m-HMPAO has been evaluated in several laboratories, and difference in methods for separation and labelling accounts for difference in efficiency, viability and biodistribution of the labelled leukocytes. We performed inflammation scan using leukocytes labelled with Tc-99m-HMPAO in three dogs 24 hours after inoculation of live E. Coli and A. Aureus in their right abdominal wall. We separated mixed leukocytes by simple sedimentation using 6% hetastarch (HES) and labelled the leukocytes with Tc-99m-HMPAO in 20% cell free plama diluted with phosphate buffer solution(Fig. 1). Uptake was high in the liver and spleen but is was minimal in the lungs on whole body scan. Kidneys and intestine showed minimal activity although it was high in the urinary bladder(Fig. 2). Uptake of labelled leukocytes in the inflammation site was do(mite on 2 hour-postinjection scan and abscess was clearly delineated on 24 hour-delayed scan with high target-to-nontarget ratio(Fig. 3, 4). Inflammation scan using mixed leukocytes labelled with Tc-99m-HMPAO is very sensitive and specific in early detection of inflammation.

• Radiation Oncology Journal
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• v.35 no.4
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• pp.368-379
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• 2017

Purpose: The purpose of this study was to explore the dosimetric difference between simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and three-dimensional conformal radiotherapy (3DCRT), and the clinical outcomes of anal squamous cell carcinoma (ASCC) chemoradiotherapy featuring SIB-IMRT. Materials and Methods: This study included ten patients with ASCC who underwent chemoradiotherapy using SIB-IMRT with 5-fluorouracil and mitomycin C. SIB-IMRT delivered 54 Gy to each primary tumor plus metastatic lymph nodes and 45 Gy to regional lymph nodes, in 30 fractions. Four patients received additional boosts to the primary tumors and metastatic lymph nodes; the median total dose was 54 Gy (range, 54 to 60 Gy). We additionally created 3DCRT plans following the Radiation Therapy Oncology Group 9811 protocol to allow dosimetric comparisons with SIB-IMRT. Locoregional control, overall survival, and toxicity were calculated for the clinical outcome evaluation. Results: Compared to 3DCRT, SIB-IMRT significantly reduced doses to the external genitalia, bladder, and intestine, delivering the doses to target and elective nodal region. At a median follow-up time of 46 months, 3-year locoregional control and overall survival rates were 88.9% and 100%, respectively. Acute toxicities were treated conservatively. All patients completed radiotherapy with brief interruptions (range, 0 to 2 days). No patient experienced ${\geq}grade$ 3 late toxicity during the follow-up period. Conclusion: The dosimetric advantages of SIB-IMRT appeared to reduce the toxicity of chemoradiotherapy for ASCC achieving high locoregional control in the extended period.

• Korean Journal of Medicinal Crop Science
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• v.25 no.4
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• Korean Journal of Radiology
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• v.23 no.9
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• pp.911-920
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• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.19-25
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• 2014

Purpose: Integrated PET/MRI has been developed recently has become a lot of help to the point oncologic, neological, cardiological nuclear medicine. By using this PET/MRI, a ${\mu}-map$ is created some special MRI sequence which may be divided parts of the body for attenuation correction. However, because an MRI contrast agent is necessary in order to obtain an more MRI information, we will evaluate to see an effect of SUV on PET image that corrected attenuation by MRI with contrast agent. Materials and Methods: As PET/MRI machine, Biograph mMR (Siemens, Germany) was used. For phantom test, 1mCi $^{18}F-FDG$ was injected in cylinderical uniformity phantom, and then acquire PET data about 10 minutes with VIBE-DIXON, UTE MRI sequence image for attenuation correction. T1 weighted contrast media, 4 cc DOTAREM (GUERBET, FRANCE) was injected in a same phatnom, and then PET data, MRI data were acquired by same methodes. Using this PET, non-contrast MRI and contrast MRI, it was reconstructed attenuation correction PET image, in which we evanuated the difference of SUVs. Additionally, for let a high desity of contrast media, 500 cc 2 plastic bottles were used. We injected $^{18}F-FDG$ with 5 cc DOTAREM in first bottle. At second bottle, only $^{18}F-FDG$ was injected. and then we evaluated a SUVs reconstructed by same methods. For clinical patient study, rectal caner-pancreas cancer patients were selected. we evaluated SUVs of PET image corrected attenuastion by contrast weighted MRI and non-contrast MRI. Results: For a phantom study, although VIBE DIXON MRI signal with contrast media is 433% higher than non-contrast media MRI, the signals intensity of ${\mu}-map$, attenuation corrected PET are same together. In case of high contrast media density, image distortion is appeared on ${\mu}-map$ and PET images. For clinical a patient study, VIBE DIXON MRI signal on lesion portion is increased in 495% by using DOTAREM. But there are no significant differences at ${\mu}-map$, non AC PET, AC-PET image whether using contrast media or not. In case of whole body PET/MRI study, %diff between contras and non contrast MRAC at lung, liver, renal cortex, femoral head, myocardium, bladder, muscle are -4.32%, -2.48%, -8.05%, -3.14%, 2.30%, 1.53%, 6.49% at each other. Conclusion: In integrated PET/MRI, a segmentation ${\mu}-map$ method is used for correcting attenuation of PET signal. although MRI signal for attenuation correciton change by using contrast media, ${\mu}-map$ will not change, and then MRAC PET signal will not change too. Therefore, MRI contrast media dose not affect for attenuation correction PET. As well, not only When we make a flow of PET/MRI protocol, order of PET and MRI sequence dose not matter, but It's possible to compare PET images before and after contrast agent injection.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.22-31
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• 2005

Purpose : To conduct a nationwide survey on the principals in radiotherapy for rectal cancer, and produce a database of Korean Patterns of Care Study. Materials and Methods : We developed web-based Patterns of Care Study system and a national survey was conducted using random sampling based on power allocation methods. Eligible patients were who had postoperative radiotherapy for rectal cancer without gross residual tumor after surgical resection and without previous history of other cancer and radiotherapy to pelvis. Data of patients were Inputted to the web based PCS system by each investigators in 19 institutions. Results : Informations on 309 patients with rectal cancer who received radiotherapy between 1998 and 1999 were collected. Male to female ratio was 59 : 41, and the most common location of tumor was lower rectum ($46\%$). Preoperative CEA was checked in $79\%$ of cases and its value was higher than 6 ng/ml in $32\%$. Pathologic stage were I in $1.5\%$, II in $32\%$, III in $53\%$, and IV in $1.6\%$. Low anterior resection was the most common type of surgery and complete resection was peformed in $95\%$ of cases. Distal resection margin was less than 2 cm in $30\%$, and number of lymph node dissected was less than 12 in $31\%$. Chemotherapy was peformed in $91\%$ and most common regimen was 5-FU and leucovorine ($59\%$). The most common type of field arrangement used for the initial pelvic field was the four field box (Posterior-Right-Left) technique ($65.0\%$), and there was no AP-PA parallel opposing field used. Patient position was prone in $81.2\%$, and the boost field was used in $61.8\%$. To displace bowel outward, pressure modulating devices or bladder filling was used in $40.1\%$. Radiation dose was prescribed to isocenter in $45.3\%$ and to isodose line in 123 cases ($39.8\%$). Percent delivered dose over $90\%$ was achieved in $92.9\%$. Conclusion : We could find the Patterns of Care for the radiotherapy in Korean rectal cancer patients was similar to that of US national survey. The type of surgery and the regimen of chemotherapy were variable according to institutions and the variations of radiation dose and field arrangement were within acceptable range.