• Journal of Pharmacopuncture
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• v.18 no.1
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• pp.63-71
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• 2015

Objectives: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. Methods: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun-Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.169-173
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• 2007

Background: Although the use of intravenous patient controlled analgesia (IVPCA) has been compared to the use of patient conrolled epidural analgesia (PCEA), there is no optimal administration route of alfentanil for the treatment of postoperative pain. This randomized double-blind study compared the efficacy of the use of IVPCA and PCEA for postoperative pain and the side effects after a total abdominal hysterectomy (TAH). Methods: Sixty patients undergoing a TAH were randomly assigned to receive either IVPCA (Group I) or PCEA (Group E) for the infusion of alfentanil for postoperative pain control. In both groups, a loading dose of $750{\mu}g$ alfentanil was administered. All patients received the same continuous infusion rate (0.3 mg/h), bolus dose (0.15 mg), and lockout time (15 min). The incidence of side effects, the VAS (visual analog scale) of pain, blood pressure, and heart rate were checked for 20 hours after the loading dose injection. Results: The VAS of pain was not significantly different between the two groups of patients. The onset of the analgesic effect was significantly more rapid in the Group I patients than in the Group E patients. There was no difference in side effects for either group. Conclusions: When considering multiple factors such as the onset of analgesia, technical difficulties or infection after the procedure, IVPCA using alfentanil is more useful than PCEA for postoperative pain control after a TAH.

• The Korean Journal of Pain
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• v.26 no.1
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• pp.14-20
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• 2013

Background: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive $ED_{50}$ of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of $ED_{50}$, or $ED_{50}$ of each drug followed by an isobolographic analysis. Results: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of $30{\mu}g$ in phase 1 (39.8% of control) and $10{\mu}g$ during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.297-305
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• 1998

This study used in vivo intracellular recording in rat hippocampus to evaluate the effect of lidocaine and MK-801 on the membrane properties and the synaptic responses of individual neurons to electrical stimulation of the commissural pathway. Cells in control group typically fired in a tonic discharge mode with an average firing frequency of $2.4{\pm}0.9$ Hz. Neuron in MK-801 treated group (0.2 mg/kg, i.p.) had an average input resistance of $3.28{\pm}5.7\;M{\Omega}$ and a membrane time constant of $7.4{\pm}1.8$ ms. These neurons exhibited $2.4{\pm}0.2$ ms spike durations, which were similar to the average spike duration recorded in the neurons of the control group. Slightly less than half of these neurons were firing spontaneously with an average discharge rate of $2.4{\pm}1.1$ Hz. The average peak amplitude of the AHP following the spikes in these groups was $7.4{\pm}0.6$ mV with respect to the resting membrane potential. Cells in MK-801 and lidocaine treated group (5 mg/kg, i.c.v.) had an average input resistance of $3.45{\pm}6.0\;M{\Omega}$ and an average time constant of $8.0{\pm}1.4$ ms. The cells were firing spontaneously at an average discharge rate of $0.6{\pm}0.4$ Hz. Upon depolarization of the membrane by 0.8 nA for 400 ms, all of the tested cells exhibited accommodation of spike discharge. The most common synaptic response contained an EPSP followed by early-IPSP and late-IPSP. Analysis of the voltage dependence revealed that the early-IPSP and late-IPSP were putative $Cl^--and\;K^+-dependent$, respectively. Systemic injection of the NMDA receptor blocker, MK-801, did not block synaptic responses to the stimulation of the commissural pathway. No significant modifications of EPSP, early-IPSP, or late-IPSP components were detected in the MK-801 and/or lidocaine treated group. These results suggest that MK-801 and lidocaine manifest their CNS effects through firing pattern of hippocampal pyramidal cells and neural network pattern by changing the synaptic efficacy and cellular membrane properties.

• Resources Recycling
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• v.5 no.3
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• pp.65-72
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• 1996

Colloidal calcium wrbonate(diametcr 0.02-0 09 m~wja s developed to maintain the mamenl of pnriide formatio~>w ~lhoutsurlace trealment. The control factors of particle size and optimum condiliuna for compound fam*tition has not bccn studiedyet. This shldy war aimed at developing a method fur compounding colloidal calcium carbonfcte to cnl~hol cubic calciumcarbonate, and then compounding the b-o types oI precipitated calcium wrbonatc under optimum wndilrans Calc~umhydroxide was calcinated at 1, lWC far two hours, md then hydrated for 30 minutes at t i i O rprn and ambiznt temperahlle.Two-liter suspension was subjected to the contact with carbon dioxide at l5"C, 600 ipxn and C0= injection in the rate of 1 Umin Two types of dcium carbonate(cuhic calcium carbonatc(0 24.9 pm) md collnidd calcium mhnnate (0.02-0 09 pm))were compounded by "wing the concentrations of calcium oxide and ihe suspension were compounded. It was found that theoptimum concentrations of each suspensions were 5 wt % and 2.5 \I*.% respectively. ' h c key control factor af thc parlicle slzcdislribution was the concenkation al the suspension. The size of compounded particles was measured by a Zcla S k r 'fieaverage particle size of the cubic calcium carbonate aas 223.4 nm(0.223 pm), and that of thc colloidal a~lciumc arbonate was93.6 nm (0.093 km). Ihe particle sizc was evenly cantlolled on a stdblc basis in an H, O reaction system.asis in an H, O reaction system.

• Korean Journal of Medicinal Crop Science
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• v.18 no.5
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• pp.323-328
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• 2010

Root extract of Lythrum salicaria reported a hepato-protective effect on $CCl_4$-induced liver toxicity of rat was prepared into fractions such as n-hexane up layer (HA), n-hexane down layer (HB), diethyl ether (E), ethylacetate (EA), n-butanol (B) and water (W). Fractions prepared were tested their activities in vitro and in vivo condition. All of the fractions showed effective antioxidant asctivities on DPPH radical and $CuSO_4$-induced oxidation of human low density lipoprotein and E fraction showed the highest inhibitory effect (98.1% at $50\;{\mu}g/m{\ell}$) on linoleic acid autoxidation at $40^{\circ}C$, which was more effective than $\alpha$-tocopherol (82.4%). Five fractions (H = HA plus HB, E, EA, B, and W, 150 mg/kg/day) were fed into Sprague Dawley, male rats for 4 days, which were intoxicated with intra-peritoneal injection of carbon tetrachloride ($1\;m{\ell}/kg$ in corn oil) at the 4th day and were sacrificed in 24 hrs. Serum tumor necrosis factor-alpha (TNF-$\alpha$), a proinflammatory cytokine, elevated with $CCl_4$-intoxication in negative control group ($83\;pg/m{\ell}$) was significantly decreased in E fraction-supplemented group ($18\;pg/m{\ell}$). Cu, Zn-superoxide dismutase (SOD) activity increased in negative control group (0.12 U/mg protein) was decreased in E fraction (0.07 U/mg protein). From the results, it is suggested that ether fraction from root extract of L. salicaria would be a potent antioxidant candidate for ameliorating liver injury induced by chemical intoxicant.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.1
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• pp.49-69
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• 2011

Objective : The object of this study was to observe the effects of Lonicerae Flos (LF) aqueous extracts on lipopolysaccharide (LPS)-induced rat acute lung injury. Method : Five different dosages of LF extracts were orally administered once a day for 28 days before LPS treatments, and then all rats were sacrificed after 5 hour-treatment of LPS. Eight groups of 16 rats each were used in the present study. The following parameters caused by LPS treatment were observed ; body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid (BALF) protein lactate dehydrogenase (LDH), and proinflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde (MDA), myeloperoxidase (MPO), proinflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ contents. In addition, the histopathologic changes were observed in the lung in terms of luminal surface of alveolus, thickness of alveolar septum, number of polymorphonuclear neutrophils. Result : As results of LPS-injection, dramatical increases in lung weights, pulmonary transcapillary albumin transit increases, increases in $PaCO_2$, decreases in pH of arterial blood and $PaO_2$, increases of BALF protein, LDH, TNF-${\alpha}$ and IL-$1{\beta}$ contents, total cells, neutrophil and alveolar macrophage ratios, TNF-${\alpha}$ and IL-$1{\beta}$ contents increases were detected with decreases in LSA and increases of alveolar septum and PMNs numbers, respectively as compared with intact control. These are means that acute lung injuries (resembling acute respiratory distress syndrome) are induced by treatment of LPS mediated by inflammatory responses, oxidative stress and related lipid peroxidation in the present study. However, these LPS-induced acute lung injuries were inhibited by 28 days continuous pretreatment of 250 and 500mg/kg of LF extracts. Because of lower three dosages of LF treated groups, 31.25 and 62.5 and 125mg/kg did not showed any favorable effects as compared with LPS control, the effective dosages of LF in LPS-induced acute lung injuries in the present study, is considered as about 125mg/kg. The effects of 250mg/kg of LF extracts showed almost similar effects with ${\alpha}$-lipoic acid 60mg/kg in preventing LPS-induced acute lung injuries. Conclusion : It seems that LF play a role in protecting the acute respiratory distress syndrome caused by LPS.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• Journal of Life Science
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• v.12 no.1
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• pp.1-7
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• 2002

The purpose of this study was designed to observe the effects of the feeding Zizyphus jujuba seed extract on the improvement of the blood glucose, lipids in the serum of streptozotocin (STZ)-induced diabetic rats fed the experimental diets for 4 weeks. Concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free-cholesterol, cholesteryl ester, triglyceride (TG) and phospholipid (PL) in serum were significantly higher in the STZ (55mg/kg B.W.)-induced diabetic group (group 2) and STZ (I.P.)+ Zizyphus jujuba seed extract group (group 3) than those in the control group (group 1, basal diet + water). But the concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free-cholesterol, cholesteryl ester, TG and PL in serum were remakably lower in the group 3 than those in the group 2. In the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration, Zizyphus jujuba seed extract administration group (group 3) were higher percentage than in the group 2. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in serum were rather lower in the Zizyphus jujuba seed extract administration group (group 3) than in the STZ- induced diabetic group (group 2). From the above results, it was suggested that the Zizyphus jujuba seed were effective on the improvement of the blood glucose, lipid compositions in serum of STZ-induced diabetic rats. Moreover, in Zizyphus jujuba seed was effective therapeutic regimen for the control of metabolic derangements in adult disease.

• Journal of Food Hygiene and Safety
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• v.21 no.4
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• pp.197-203
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• 2006

Parabens are most wildly used in food, cosmetics and pharmaceutic products as preservatives caused of safety and cheap. we had examined that paraben had estrogenic activity through the in vivo and in vitro experiments in last year. We demonstrated that most of parabens(ethyl, butyl, propyl, isobutyl, isopropyl) increased significantly uterus weight as well as induced proliferation of MCF-7 cell and binding of estrogen receptor as endocrine disrupter compounds. In this study, we evaluated that whether parabens have effect on male reproductive system or not. the male rats were administrated parabens by oral injection then examined separation of preputial day for $PND23\simPND52$. As the results, most parabens delayed pubertal development compare to control group. The separation of preputial day of Butyl and Propyl parabens at high concentration were PND 44 days and PND 45days compared to control group as PND 40 days. Even though, parabens as endocrine disrupter wildly spread in food, cosmetics and pharmaceutic products, we didn't have the safe guideline. In abroad, they are re-evaluating safety assessment for parabens. In conclusion, parabens delayed pubertal development in juvenile parabens are consider as endocrine disrupter chemicals.