• Clinical and Experimental Pediatrics
• /
• 제50권6호
• /
• pp.531-535
• /
• 2007

Purpose : Indomethacin treatment is successful in about 90% of patent ductus arteriosus (PDA) in premature infants, but in some, repeated administration or surgical closure is required. The object of the present study is to determine the factors affecting the efficacy of indomethacin treatment and to predict the treatment result. Method : The 29 preterm neonates, admitted to neonatal intensive care unit of Kyunghee university medical center and Eulji university hospital between September 2002 and April 2006 were diagnosed of PDA and treated with indomethacin. The risk factors that might affect the efficacy of treatment were studied retrospectively. Results : The single-administered group was 19 patients out of 29 (65.5%) and among the repeated-administered group, 5 patients (17.2%) had repeated indomethacin administration and the other 5 patients (17.2%) underwent surgery due to reopening of the duct after repeated medical treatment. In repeated-administered group, the diameter of PDA was significantly larger ($3.66{\pm}0.8mm$ vs $2.55{\pm}0.8mm$, P<0.01), especially when larger than 3.5 mm (sensitivity: 70%, specificity: 89%). Also, the mean postnatal age of the first indomethacin administration was significantly delayed in repeated-administered group (19.7 days vs 12.5 days, P<0.05). There were no significant differences in gestational age (32 wk 5 days vs 30 wk 8 days) and in birth weight (1598.9 g vs 1750.5 g). There were no significant differences in associated morbidities. Conclusion : In patients with larger diameter of PDA (>3.5 mm) and older postnatal age (>7 days), the effect of indomethacin was decreased. Therefore in such cases, repeated dose of indomethacin or surgical ligation should be considered earlier.

• Journal of Applied Biological Chemistry
• /
• 제58권2호
• /
• pp.139-143
• /
• 2015

In the present study, we investigated the oral toxicity of Amomum tsao-ko Crevost et Lemaire, (Zingiberaceae) extract in Balb/c mice (BALB, n=60) for 3 weeks. Balb/c mice (10 mice/group, 6 group, $20{\pm}2g$, 6 weeks) were orally administered for 21 days, with dosage of 250, 500, 1000, 2000 mg/kg/day. Ethanol extract of A. tsao-ko did not affect any significant change of mortality, clinical signs, organs and body weights. Also, there were not significantly difference from the naive group (control) in hematological and serum biochemical examination. Consequently, these findings indicate that 3-week treatment with the ethanol extract of A. tsao-ko was not any toxic effects in Balb/c mice and the no-observed adverse effect level (NOAEL) for oral toxicity was determined to be 2000 mg/kg/day under our experimental conditions.

• Journal of the Korean Society of Food Science and Nutrition
• /
• 제36권8호
• /
• pp.975-982
• /
• 2007

The purpose of this study was to investigate repeated-dose toxicity in male and female rats orally administered with Pediococcus pentosaceus MD1, an anti-Helicobacter pyroli producing lactic acid bacteria isolated from kimchi. Sprague-Dawley rats were divided into 4 groups, 10 animals in each group. The test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg for 4 weeks. No test article-related deaths and clinical findings in both sexes of rats during the study period were resulted. In addition, no differences were found between control and treated groups in body weight changes, food intake consumption and water consumptions. Hematological parameters, serum biochemical analysis and any other findings did not also show any significant or dose-dependent alterations. There were no alterations in absolute and relative organ weights by the administration of Pediococcus pentosaceus MD1. These results suggest that no-observed-adverse-effect level (NOAEL) of Pediococcus pentosaceus MD1 is considered to be more than 2 g/kg in male and female rats.

• Toxicological Research
• /
• 제16권2호
• /
• pp.163-172
• /
• 2000

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

• Biomolecules & Therapeutics
• /
• 제2권3호
• /
• pp.270-280
• /
• 1994

This study was conducted to evaluate the repeated dose toxicity of DA-3030, a recombinant human granulocyte colony stimulating factor(rhG-CSF), in rats. DA-3030 was administered intravenously once a day for 4 weeks to 20 males and 20 females per group at doses of 0(control), 115 and 1150 $\mu\textrm{g}$/kg, and to 15 males and 15 females per group at doses of 1.15 and 11.5$\mu\textrm{g}$/kg. After the administration period, 5 males and 5 females per group in the 0,115 and 1150 $\mu\textrm{g}$/kg groups were placed on withdrawal for 2 weeks. Through-out the study, all the rats survived. The administration of DA-3030 induced, a marked increase in the number of peripheral neutrophils, elevation of serum alkaline phosphatase activity, and splenomegaly in the rats of both sexes receiving 115 or 1150 $\mu\textrm{g}$/kg. Histopathologic examination revealed extramedullary granulopoiesis in spleen and liver, and increase in the number of activated macrophages in spleen in rats of both sexes in 115 and 115 $\mu\textrm{g}$/kg groups, and increased M/E ratio in 11.5, 115 and 1150$\mu\textrm{g}$/kg groups. Most of the changes produced by DA-3030 were thought to be attributable to exaggerated pharmacological effect of the drug, and subsided or disappeared after the recovery period. Under the present condition, no effect dose of DA-3030 is estimated at 1.15 $\mu\textrm{g}$/kg/day.

• Journal of Yeungnam Medical Science
• /
• 제4권1호
• /
• pp.89-96
• /
• 1987

Carbon tetrachloride and Dimethylnitrosamine, both potent hepatotoxic agents, affect the hepatic lobules with fatty changes and central necrosis, and hemorrhagic necrosis. To study the effects on morphologic changes of the hepatic lobules in cases of single and repeated treatment of both hepatotoxins, sublethal doses of carbon tetrachloride, 0.4ml/kg, and dimethylnitrosamine, 40mg/kg of rats were given intraperitoneally single, twice and triple. With interval of 3 days, and the results were as follows : 1. The fatty changes and central necrosis of the hepatic lobules were milder and more quickly disappeared in the rats with twice or triple treatment than single administration of carbon tetrachloride, and regenerative changes of hepatic and sinusoidal cells achieved fater in the rats with repeated administration of carbon tetrachloride than those with single treatment. 2. The hemorrhagic necrosis of the hepatic lobules was not significantly influenced by the times of DMN treatment, but the hyperplastic changes showed more active to animals, with multiple administration of DMN.

• Journal of the Korean Society of Food Science and Nutrition
• /
• 제41권11호
• /
• pp.1534-1539
• /
• 2012

This study was conducted to evaluate the possible subacute toxicity of gamma-irradiated Tarakjuk. Tarakjuk was irradiated at a dose of 30 kGy at room temperature. For the animal study, AIN-93G as a control diet and 30 kGy irradiated and non-irradiated Tarakjuk diets were administered to male and female ICR mice (10 mice per group) for 3 months. During the experimental period, the group fed 30 kGy irradiated Tarakjuk did not show any changes in appearance, behavior, mortality, body weight, organ weight, or food consumption compared to control. Further, all biochemical parameters were in normal ranges. In the histopathological examination of liver and kidney tissues of ICR mice, there were no significant differences between the control and 30 kGy irradiated Tarakjuk groups. These results indicate that Tarakjuk irradiated at 30 kGy did not cause any toxic effects under these experimental conditions.

• Toxicological Research
• /
• 제20권3호
• /
• pp.273-280
• /
• 2004

The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.

• YAKHAK HOEJI
• /
• 제41권2호
• /
• pp.203-211
• /
• 1997

This study was conducted to investigate the subacute transdermal toxicity of Syndella gel, a new topical drug containing deproteinized dialysate of calf's blood and micronomicin sulfate in Sprague-Dawley rats. Three doses (1.97, 3.94, 7.88 g/kg) of Syndella gel was daily treated transdermally to male and female rats for 30 days. No death was occurred in either control or treated rats. No significant toxic clinical signs and body weight change were not observed at any doses in the male or female rats treated. There were no significant alterations in hematologic and biochemical parameters in both sexes, however slight increase of potassium concentration was observed in 3.94g/kg and 7.88 g/kg female groups. No significant necrotic changes were not observed in examined organs. This study showed that up to 7.88g/kg Syndella gel did not induce subacute transdermal toxicity.

• Biomolecules & Therapeutics
• /
• 제4권1호
• /
• pp.19-31
• /
• 1996

This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.