• The Korean Journal of Food And Nutrition
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• v.30 no.4
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• pp.665-672
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• 2017

The anti-diabetic effect of dried-silkworm Dongchunghacho water extracts was investigated in streptozotocin (STZ)-induced diabetic rats. Seven-week-old SD rats were randomly assigned to six groups: normal control (NC) group, diabetic control (DC) group, water extracts of Paecilomyces japonica grown on a dried-silkworm (PJ-DS, 50 mg/kg) group, PJ-DS (250 mg/kg) group, water extracts of Cordyceps militaris grown on a dried-silkworm (CM-DS, 250 mg/kg) group, and water extracts of dried-silkworm (DS, 250 mg/kg) group. These groups were orally provided with sample dissolved in water respectively for four weeks after an injection of STZ (60 mg/kg, ip) followed by identification of diabetic control (DC) group. After four weeks, body weight of all diabetic groups was significantly lower than that of the normal control (NC) group, but among diabetic groups there were no significant differences. Blood glucose levels of the PJ-DS (50 mg/kg), PJ-DS (250 mg/kg), CM-DS (250 mg/kg) and DS (250 mg/kg) groups were reduced compared to the DC group by 3.0 percent, 18.5 percent, 6.9 percent and 13.1 percent, respectively. Concentration of total cholesterol and triglyceride in blood plasma were to some degree decreased in PJ-DS (250 mg/kg) and DS (250 mg/kg) groups compared to the DC group. According to these results dried-silkworm Dongchunghacho water extracts (PJ-DS) boost protection against STZ-induced toxicity.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.127-137
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• 1996

This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.3
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• pp.233-244
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• 2006

Of many volatile organic detergents for metals, benzine(CAS No. 8030-30-6), of which the toxicity has not yet been proven, has been used as an alternative of the halide compounds in the consideration of toxic effects, global warming and the destruction of ozone layer. In order to evaluate the effects of the benzine on human body by investigating the subchronic inhalation toxicity, to obtain the basic data for establishing the criteria of exposure in working environments and to classify the hazardousness in compliance with the Industrial Safety and Health Act by evaluating the hazardousness, repeated inhalation exposure test was carried with SD rats. The rats were grouped by 10 females and males each. The repetitive inhalation exposures were carried out at 4 levels of concentration of 0 ppm, 60 ppm, 300 ppm, and 1,500 ppm, for 6 hours a day, 5 days a week, for 13 weeks. The results are described hereunder. 1. No death of the animals of the exposed and controlled groups in the test period. Not any specific clinical symptoms, change in feed intake quantity, abnormality in eye test, or change in activity were observed. 2. In the 300 ppm and 1,500 ppm groups, weight reduction in the female groups and weight increase of liver and kidney in the male groups compared with control group were observed with statistical significance(p<0.05). 3. In the blood test, the HCT increased in the male 300 ppm group and the number of hematocyte increased, MCV and MCH decreased in the male 1,500 ppm group. In the female 1,500 ppm group, the HB decreased and the distribution width of the hematocyte particle size increased. In the blood biochemistry test, the TP in the male 1,500 ppm group and the LDH in the female 1,500 ppm group were increased with statistical significance(p<0.05). 4. Under the test conditions of the present study with SD rats, the NOEL was evaluated to be from 60 ppm to 300 ppm for both male and female groups. By extrapolation, the NOEL for human who work 8 hours a day was evaluated to be from 128 ppm to 640 ppm 5. Since the NOEL evaluated in this study do not exceed 60ppm(0.184 mg/L) the test material does not belong to the classification of the hazardous substance "NOEL${\leq}$0.5mg/L/6hr/90day(rat), for continuous inhalation of 6hours a day for 90 days" nor to the basic hazardous chemical substance class 1(0.2 mg/L/6hr/90day(rat) defined by the GHS which is a criteria of classification and identification of chemical compounds. However, considering the boiling point($30-204^{\circ}C$), flashing point($-40^{\circ}C$), vapor pressure(40 mmHg), and the inflammable range(1.0 - 6.0 %), sufficient care should be taken for handling in the safety aspects including fire or explosion.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.355-361
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• 1993

Since May 1991, authors have conducted a pilot study to determine the feasibility and evaluate the effect of concurrent radiation therapy and chemotherapy with 5-FU and Cis-platinum for locally advanced cervical cancer (stage IIB-IVA). Radiation therapy consisted of external irradiation to whole pelvis (4140 cGy/23 fx) in 4.5 weeks followed by high dose rate intracavitary radiation therapy (HDR ICRT) to deliver a dose of 30 to 35 Gy to A point in 6 to 7 fractions. After the intracavitary radiation therapy, parametrial boost was delivered for B point dose of 60 Gy in Stage IIB and 65 Gy in stage IIIB. 5-FU (1000 $mg/m^2/24hr$ for 96 hour iv infusion) and Cis-platinum (20 $mg/m^2/day$ IV bolus for 3 days) were given during the second week of external RT and the second course chemotherapy administered at the first HDR ICRT with the same method as the first chemotherapy. Sixteen patients (10 stage IIB,4 stage IIIB,2 stage IVA) were registered to this protocol. Among these 16 patients, two refused treatment after 2 fractions of external irradiation, and one could not continue intracavitary irradiation because of treatment related genitourinary toxicity. So 14 patients were evaluated for toxicity and 13 patients were evaluated for response analysis. Five of 14 patients developed grade 3 gastrointestinal toxicity but 4 of them recovered at the completion of treatment. One stage IIIB patient with inguinal lymph node metastasis who received higher dose of radiation in spite of initial poor performance status did not recover from gastrointestinal toxicity at the completion of treatment. And she died of distant metastasis at one month after the completion of treatment. Two of 14 evaluable patients showed weight loss, more than $10\%$ of initial weight. One patient developed grade 3 leukopenia. In this study, the average total treatment period of completely treated patients was 75 days and three of them took more than 80 days (84, 84, 89 days). Toxicities were generally acceptable and there were no treatment related death. At the last follow-up, complete response was achieved in $62\%(8/13)$ and especially of nine patients with stage IIB, eight patients showed complete response. This study suggests that concurrent radiation therapy and chemotherapy (5-FU and Cis-platinum) is tolerable and effective. Further follow-up is needed to determine whether this protocol will have a favorable impact on survival and to evaluate the late effect on normal tissues. In future, prospective randomized trials are needed to compare the standard radiation therapy alone with concurrent chemotherapy and radiation therapy for locally advanced cervical carcinoma.

• Environmental Mutagens and Carcinogens
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• v.18 no.1
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• pp.22-25
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• 1998

Anticarcinogenic activity of astaxanthin-containing egg yolks (designate AEY) was investigated for 7,12-dimethylbenz[a]anthracene (DMBA)-induced two stage mouse epidermal carcinogenesis. Female ICR mouse (6-7 weeks of age) were house in a humidity-and-temperature-controlled facility and subjected to feed and water ad libitum. AEY (10 mg/0.2 ml acetone) was painted on the back of mice 7 days, 3 days and 5 min before DMBA treatment (50 nmole/0.2 ml acetone). One week later after DMBA treatment, 6 ${\mu}g$ tetradecanoyl 12-phorbol 13-O-acetate (TPA) dissolved in 0.2 ml acetone was applied on the mouse twice weekly over a period of 22 weeks. No sample was given to control mice. Control egg yolk (CEY) and astaxanthin-containing oil (designate AO) from Phaffia rhodozyma were used as positive controls. Mouse treated with AEY exhibited 10 tumors per mouse whereas control mouse exhibited 15 tumors per mouse, the fact that 33% reduction of tumor per mouse by AEY treatment. Tumor incidence was also reduced to 15% by AEY treatment when compared to that of control group. Such effects were also seen in CEY and AO treatment groups, but leaser extent. AO gave reduction of food intake and body weights relative to those of AEY and CEY, indicating toxicity of AO. These results suggest that AEY exhibits anticarcinogenic activity for DMBA-induced mouse epidermal carcinogenesis.

• Applied Microscopy
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• v.15 no.1
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• pp.13-30
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• 1985

This study was undertaken to investigate the effect of lead on organisms. Mice received 15mg or 30mg of lead acetate per kg body weight every day for 1, 2 or 3 weeks, and the livers and kidneys were removed 24h after repeated injections. The livers and kidneys were used as sources for measurement of enzyme activities and for observation of alterations in ultrastructure. It was observed that body weights of mice treated with lead acetate were decreased when compared with those before treatment. This decrease in body weight was proportional to dose. The enzyme activities of succinate and malate dehydrogenases of experimental group that was treated with lead acetate for 1 week were nearly unchanged when compared with controls, but the enzyme activities of experimental group that was treated with lead acetate for 2 or 3 weeks were lower than those of controls. Changes in the enzyme activities were dependent on, but were not proportional to dose. Histologic examination of livers and kidneys after lead treatment showed that lead compound was accumulated and damaged in nucleus and mitochondria mainly. It was also observed that intranuclear inclusion bodies were formed only in epithelial cell of kidney proximal tubule after lead treatment. The overall changes in the ultrastructure were much greater in the livers than in the kidneys. From the above results, it nay be possible to conclude that the lead results in the decrease in body weight, reduction in the succinate dehydrogenate and malate dehydrogenase activities, and damages in the ultrastructure of kidney and liver in mouse. The presence of intranuclear inclusion bodies only in the kidney implies that these bodies protect the kidney from lead toxicity to some extent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1210-1218
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• 2007

Recently Atopic Dermatitis(AD) is increasing along with allergic disease. At present, there is no infallible cure for AD. Then AD patients undergo great suffering. This study is carried out to see whether or not the administering Danggwieumja(DG) along with Samhwangseje-gamibang(SG} as a medicine for external aplication, is effective in treating atopic dermatitis. To examine the effectiveness of the above prescription, the author made an observation of diverse immune responses. through the model of NC/Nga atopic mice. Results provided evidence that the DG administration along with SG can be used as a treatment means to atopic dermatitis. The results are as follows: The extent of Clinical skin severities in 13 and 16 week old NC/Nga mice treated with DG and SG, were reduced by 50.9%, 53.9% respectively, compared to the control NC/Nga mice with no drug treatment. IgE, IL-4, IL-5, IL-6, IgM and IgG1 levels in the serum of the NC/Nga mice treated with DG and SG were significantly decreased compared to those of the untreated control mice. In contrary, to the $IFN-{\gamma}$ level, significantly increased. The spleen weight of the NC/Nga mice treated with DG and SG significantly decreased compared to those of the untreated control mice. CCR3 gene expression in the skin tissue of NC/Nga mice treated with DG and SG were highly decreased, and the IL-6 expression significantly decreased, and the $IFN-{\gamma}$ gene expression increased compared to those of the untreated control mice. Histological observation of the ear and dorsal skin tissue of the NC/Nga mice treated with DG and SG, showed that the extents of inflammation and infiltrated immune cells in the epidermal tissue and dermis, were highly reduced compared to those of the untreated control mice. In the model inducing COX-2 activity in RAW 264.7 cell, the denser DG became, the more COX-2 activity was inhibited, compared to those of the untreated control group. $IL-1{\beta}$, and $TNF-{\alpha}$, IL-6 gene expression in RAW 264.7 cell with DG, significantly decreased, compared to those of the untreated control group. According to the assessment of cell toxicity in L929 cell, the rate of cell multiplication increased by 3% in consistency to 100ppm of DG compared to the untreated control group and in more than the 200 ppm consistency, cell toxicity was occurred.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.154-162
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• 2006

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6129-6132
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• 2012

Objectives: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) and concurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. Methods: Forty-one patients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrent weekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of $45mg/m^2$ was administered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeks after the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). Results: All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patients due to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patients completed the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course. Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The median follow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS), and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and T or N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively. Conclusion: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approach in the treatment of locally advanced NPC.