• Journal of Ginseng Research
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• 제29권4호
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• pp.176-181
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• 2005

Our previous reports demonstrated that ip. administration of Korean red ginseng acidic polysaccharide (RGAP) exerts antitumor activity In mice. The present study was carried out to compare the effects of ip. and p.o. routes of administration of RGAP on either normal or tumor-bearing BALB/c mice. RGAP was administered either ip. or p.o. at doses of 100, 300, 500, 1000 mg/kg for 1 or 5 weeks. Peritoneal macrophages from mice treated with RGAP p.o. at a dose of 300 mg/kg either for 1 or 5 weeks did not exhibit growth inhibition activity toward WEHI-I64 tumor cells. However, administration of RGAP at a dose of 600 mg/kg for both 1 and 5 weeks increased the antitumor activity of macrophages. Oral administration of RGAP (600 mg/kg) for 5 weeks and ip. administration of RGAP (300 mg/kg) for 1 week resulted in antitumor activities of $40\%$ and $45\%$, respectively, indicating that the effect of i.p. injection is more potent 2 and 5 times than that of p.o. one in terms of dose and duration, respectively. Tumor inhibition rates of RGAP at doses of 300, 500, 1000 mg/kg in mice transplanted with B16-F10 melanoma were 4.4, 12.0, and $45.4\%$, respectively, meaning that p.o. dose higher than 500 mg/kg possess marked antitumor activity. The results above suggests that p.o. administration of RGAP also show antitumor activity in vivo depending on the dose.

• Imaging Science in Dentistry
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• 제37권2호
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• pp.65-68
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• 2007

Purpose: To compare the leakage and scattered radiation from hand-held dental X-ray unit with radiation from fixed dental X-ray unit. Materials and Methods: For evaluation we used one hand-held dental X-ray unit and Oramatic 558 (Trophy Radiologie, France), a fixed dental X-ray unit. Doses were measured with Unfors Multi-O-Meter 512L at the right and left hand levels of X-ray tube head part for the scattered and leakage radiation when human skull DXTTR III was exposed to both dental X-ray units. And for the leakage radiation only, doses were measured at the immediately right, left, superior and posterior side of the tube head part when air was exposed. Exposure parameters of handheld dental X-ray unit were 70 kVp, 3 mA, 0.1 second, and of fixed X-ray unit 70 kVp, 8 mA, 0.45 second. Results: The mean dose at the hand level when human skull DXTTR III was exposed with portable X-ray unit $6.39{\mu}Gy$, and the mean dose with fixed X-ray unit $3.03{\mu}Gy$ (p<0.001). The mean dose at the immediate side of the tube head part when air was exposed with portable X-ray unit was $2.97{\mu}Gy$ and with fixed X-ray unit the mean dose was $0.68{\mu}Gy$ (p<0.01). Conclusions: The leakage and scattered radiation from hand-held dental radiography was greater than from fixed dental radiography.

• 대한본초학회지
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• 제28권1호
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• pp.15-21
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• 2013

Objectives : To evaluate the safety of KOB, a polyherbal medicine for allergic rhinitis, we conducted a subchronic toxicology study. Methods : Dried extract of KOB(Lot. No. 11003, yield : 41.1%) was prepared from GLP company (Hanpoong Pharm & Food Co., Ltd). KOB was repeatedly administrated orally of male SD rats at daily dose levels of 500 (G2), 1250 (G3) and 5000 (G4) mg/kg/day for 13 weeks. We recorded the clinical signs of toxicity, body weight, food intake/consumption, optometry, urine analysis, organ weights, hematology, and conducted serum biochemical analysis, necropsy, gross and histological changes in target organs of Sprague-Dawley rats, and clinical chemistry analysis. Results : Neither death nor any toxicological signs were obserbed in KOB at all doses of 500, 1250 and 5000 mg/kg/day during the administration period for thirteen-week. Furthermore, there was no difference in body weight and food-take consumption, optometry, necropsy, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of KOB, during at the observation period for thirteen-week. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from repeated-dose administration of KOB in rats during the observation period. Conclusions : Based on these results, the no observable adverse effect level (NOAEL) of KOB was considered to be 5000 mg/kg/day for male rats under these study conditions.

• 대한본초학회지
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• 제28권2호
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• pp.61-65
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• 2013

Objectives : Samchulgeonbi-tang (shenzhujianpi-tang) has been prescribed as one of traditional herbal medicine for treatment of stomach diseases since ancient time in Korea. Samchulgeonbi-tang extract was fermented by Lactobacillus spp. for improving the effect. However, the toxicity and safety of fermented Samchulgeonbi-tang (FS) extract were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of FS extract. Methods : To evaluate the acute toxicity and safety of FS extract, several doses of FS extract, 0, 500, 1000 and 2000 mg/kg, were orally administered to 20 male and 20 female ICR mice, respectively. After treatment with FS extract, we observed mortality, general toxicity, behavior and change of body weight for the 14 days. After 14 days of oral administration, all mice were sacrificed and hematological parameters were analyzed from blood serum. Results : In present study, the toxic signs such as mortality or abnormal behaviors by FS extract were not observed. There are no significant differences between FS-treated group and control group in body weight, organ weights, and hematological parameters. Conclusions : The remarkable adverse effects by FS extract were not observed in ICR mice. Also, any death was not occurred at all treated FS doses, 500, 1000 and 2000 mg/kg. Therefore, the approximate lethal dose (ALD) of FS extract may be more than 2000 mg/kg.

• International Journal of Oral Biology
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• 제34권2호
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• pp.87-95
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• 2009

Porphyromonas gingivalis is a major etiologic agent of chronic periodontitis and cytokines produced by macrophages play important roles in the pathogenesis of periodontal diseases. In this study we investigated the cytokine response of phorbol myristate acetatedifferentiated THP-1 cells exposed to P. gingivalis. Compared with the prominent cell wall components of P. gingivalis (lipopolysaccharide and the major fimbrial protein FimA), live P. gingivalis stimulated much higher levels of cytokine production. In addition, whereas low multiplicity of infection challenges (MOI=10) of P. gingivalis 381 stimulated high levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-1${\beta}$, high dose challenges with this bacterium (MOI = 100) resulted in a substantially diminished production of MCP-1 and IL-6. Moreover, high MOI P. gingivalis challenges achieved only low levels of induction of MCP-1 and IL-6 mRNA. The decreased production of MCP-1 and IL-6 appeared to be mediated by P. gingivalis proteases, because high MOI challenges with congenic protease mutant strains of this microorganism (MT10 and MT10W) did not result in a diminished production of MCP-1 and IL-6. Similar to its protease mutant strains, leupeptin (a protease inhibitor)- treated P. gingivalis at high doses induced high levels of MCP-1 production. To examine the mechanisms underlying the diminished production of MCP-1 by P. gingivalis proteases, the activation of mitogen-activated protein (MAP) kinases and NF-${\kappa}$B was compared between the 381 and MT10W strains. Whilst high doses of both 381 and MT10W similarly activated the three members of the MAP kinase family, the DNA binding activity of NF-${\kappa}$B, as revealed by gel shift assays, was greatly increased only by MT10W. Taken together, our data indicate that P. gingivalis stimulates the production of high levels of TNF-${\alpha}$, IL-1${\beta}$, IL-6, and MCP-1 but that high dose challenges with this bacterium result in a diminished production of MCP-1 and IL-6 via the protease-mediated suppression of NF-${\kappa}$B activation in THP-1 macrophagic cells.

• 동의신경정신과학회지
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• 제23권2호
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.

• Imaging Science in Dentistry
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• 제36권1호
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• pp.33-40
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• 2006

Purpose : To investigate clusterin expression in the acini and ductal cells of rat submandibular glands after Co-60 gamma irradiation. Materials and Methods : The male Sprague-Dawley rats weighing approximately 250 gm were divided into control and experimental groups. The experimental group was irradiated with a single absorbed dose of 2, 5, 10, and 15 Gy on the head and neck region. All the rats were sacrificed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimens including the submandibular gland were sectioned and observed using a immunohistochemical method. Results : In the 2 Gy group, clusterin expression was similar to that of the control group at 1 day after irradiation and it was observed in the striated ductal cells at 3 days after irradiation. In the 5 Gy group, clusterin expression was observed in the striated ductal cells at 1 day after irradiation and gradually increased in the 10 and 15 Gy groups. In the 15 Gy group, clusterin expression was prominent in the striated ductal cells at 1 day after irradiation, but it gradually decreased with the experimental period. The destruction of the striated ductal cells was observed in the 2 Gy group at 21 days after irradiation and in the 5, 10, and 15 Gy groups at 7 days after irradiation. The destruction of the acinar cells was observed in the 2 Gy group at 28 days after irradiation and in the 5, 10, and 15 Gy groups at 14 days after irradiation. Conclusion : Clusterin expression was induced by low doses of irradiation and it appeared to be involved in the regulation of cellular response to irradiation.

• Toxicological Research
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• 제34권1호
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• The Korean Journal of Pain
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• 제27권1호
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• pp.54-62
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• 2014

Background: The recently known analgesic action mechanisms of nefopam (NFP) are similar to those of anticonvulsants and antidepressants in neuropathic pain treatment. It is difficult to prescribe high doses of oral neuropathic drugs without titration due to adverse effects. Unfortunately, there are few available intravenous analgesics for the immediate management of acute flare-ups of the chronic neuropathic pain. The aim of this study was to determine the additional analgesic effects for neuropathic pain of NFP and its adverse effects during the titration of oral medications for neuropathic pain among inpatients with postherpetic neuralgia (PHN). Methods: Eighty inpatients with PHN were randomly divided into either the NFP or normal saline (NS) groups. Each patient received a 3-day intravenous continuous infusion of either NFP with a consecutive dose reduction of 60, 40, and 20 mg/d, or NS simultaneously while dose titrations of oral medications for neuropathic pain gradually increased every 3 days. The efficacy of additional NFP was evaluated by using the neuropathic pain symptom inventory (NPSI) score for 12 days. Adverse effects were also recorded. Results: The median NPSI score was significantly lower in the NFP group from days 1 to 6 of hospitalization. The representative alleviating symptoms of pain after using NFP were both spontaneous and evoked neuropathic pain. Reported common adverse effects were nausea, dizziness, and somnolence, in order of frequency. Conclusions: An intravenous continuous infusion of NFP reduces spontaneous and evoked neuropathic pain with tolerable adverse effects during the titration of oral medications in inpatients with PHN.

• Journal of Dental Anesthesia and Pain Medicine
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• 제21권1호
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• pp.29-39
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• 2021

Background: Impacted mandibular third molar removal is one of the most commonly performed oral surgical procedures. This procedure can lead to several postoperative complications, such as trismus, facial swelling, and pain, which occur as a result of the inflammatory responses to surgery. This study compared the efficiency of preoperative injections of 4 mg versus 8 mg dexamethasone into the pterygomandibular space to reduce postoperative sequelae. Methods: This was a randomized, prospective, split-mouth, controlled study, including 52 mandibular third molar surgeries in 26 patients. Each patient was randomized to either the 4 mg or 8 mg dexamethasone injection group. Dexamethasone was injected into the pterygomandibular space after numbness from local anesthesia. Data were collected for trismus, facial swelling, visual analog scale (VAS) pain score, and the number of analgesics taken during the evaluation period. The level of significance was set at P < 0.05. Results: Statistically significant differences in postoperative facial swelling (P = 0.031, diff = 1.4 mm) and pain (P = 0.012, diff = 0.020) were found between the 8 mg and 4 mg dexamethasone groups. However, there were no significant differences between the groups for trismus and the total number of analgesics consumed (P > 0.05). Conclusion: Compared to the 4 mg preoperative dexamethasone injection, the 8 mg preoperative dexamethasone injection into the pterygomandibular space was more effective in reducing postoperative swelling and pain following the surgical removal of the impacted mandibular third molar. However, the difference in trismus could not be evaluated clinically. Therefore, the recommendation of administering the 4 mg dexamethasone preoperative injection is optimal in the third molar surgical procedure.