• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.393-399
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• 2006

Ketamine, one of general anesthetics for human and veterinary use, is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids. It has been reported to impair various leukocyte functions. In this study, the effect of ketamine on the oxidative burst activity (OBA) of canine peripheral blood leukocytes was examined. The OBA of canine peripheral blood phagocytes was analyzed by flow cytometry system. Ketamine at higher concentration such as $1,000{\mu}M$ exhibited a low viability of leukocytes. Thus, ketamine was used at concentration of 10 to $500{\mu}M$ showing no cytotoxic effect and high cell viability. The OBA of leukocytes in the presence or absence of latex beads was analyzed by addition of dihydrorhodamine 123. The direct treatment of ketamine revealed the inhibitory effect on the OBA of peripheral blood polymorphonuclear cells (PMN) and monocyte-rich cells but not peripheral blood mononuclear cells (PBMC) in the presence of latex beads. However, when latex beads were not added to PMN, its OBA was not inhibited by ketamine. The OBA of PMN and monocyte-rich cells but not PBMC in the presence of latex beads was also inhibited by culture supernatant from ketamine-treated- PBMC but not -PMN. But the OBA of PMN in the absence of latex beads was not inhibited by culture supernatant from PBMC treated with ketamine. Therefore, these results suggested that ketamine has the inhibitory effect on the OBA of canine peripheral blood phagocytes such as neutrophils and monocytes during phagocytic response.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.29-37
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• 1994

Inhibition of the nociceptive Tail Flick Reflex (TFR) was observed with electrical stimulation of the locus coeruleus/subcoeruleus (LC/SC) in the male Sprague - Dawley rats under light anesthesia, and the involved neurotransmitter (s) were characterized. Electrical stimulation of LC/SC induced the analgesia with the stimulation threshold (intensity of the current, given for 100 usec and in 100 Hz frequency, which caused the TF latency longer than 6.5 sec) around 55 uA. Intrathecal administrations of ${\alpha}_2$ antagonist, yohimbine (30 ug) or opioid antagonist, naloxone (20 ug) increased the stimulation threshold by 147% and 123% respectively (from 55 uA to 135 uA,9 and from 54 uA to 123 uA;P0.01, n=5, each). The basal TF latency without stimulation (3.1 sec) was reduced by the antagonists (to 2.5 sec by yohimbine, p<0.05, n=5; to 2.6 sec by naloxone, p<0.1, n=5), vehicle only did not show any effect. Noradrenaline(NA) in the spinal cord superfusates measured with HPLC was increased by the LC/SC stimulation, from 4.18 ng/ml before to 7.74 ng/ml after stimulation (P<0.05, n=10). The result suggest that analgesia induced by LC/SC stimulation is mediated, at least in part, by the noradrenergic system in which ${\alpha}_2$ receptor is involved, as well as the opioid system.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.3
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• pp.40-60
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• 2012

Objectives: The object of this study was to observe antitumor, anticachexia and immunomodulatory effects of Shipyeukmiyeugi-eum(SYM) on human breast cancer cell, MCF-7, xenograft Balb/c nu-nu nude mice. Methods: Three different dosages of SYM-125, 250 and 500 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation, and the changes on the body weights, tumor volume and weights, weights of spleen and popliteal lymph node and epididymal fat, serum IL-6 and IFN-${\gamma}$ levels, NK cell and peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were observed. In addition, histopathological observations of apoptotic cell, spleen, popliteal lymph node and cervical brown adipose were also detected. The results were compared with a potent cytotoxic estrogen receptor antagonist, Tamoxifen 20 mg/kg treated mice. Results: Tumor volumes and weights were decreased without cytotoxic effects on the both MCF-7 and MCF-10A cells as results of all three different dosages of SYM treatment. And weights of body, spleen, popliteal lymph node, epididymal fat, serum IFN-${\gamma}$, NK cell, peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were increased with decrease of serum IL-6. At histopathological observations, apoptotic tumor cells, spleen, popliteal lymph node and cervical brown adipose tissue were increased. That means tumor-related immunosuppress and cachexia were markedly inhibited by SYM treatment as compared with tumor-bearing mice. On the other hand, Tamoxifen showed marked cytotoxic effects against MCF-7 and MCF-10A, decreases of tumor volume and weights, and increases of apoptotic tumor cells and related decreases of tumor cell volumes, but tamoxifen markedly deteriorated the tumor-related immune-suppress and cachexia. Conclusions: The results obtained in this study suggest that SYM showed favorable anticancer effects and anticachexic effects on the MCF-7 cell xenograft through immunomodulatory effects. SYM did not induce any cytotoxic effects against both normal and cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.5
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• pp.649-656
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• 2015

The protective effect of zinc against cortisol-induced cell injury was examined in rainbow trout gill epithelial cells. Cells exposed to cortisol for 24 h showed increased leakage of lactate dehydrogenase (LDH) as well as decreased cell viability in a dose-dependent manner. Treatment with zinc ($100{\mu}M$ $ZnSO_4$) reduced the severity of both LDH release and cell death as well as protected cells against cortisol-induced caspase-3 activation, indicating reduction of apoptosis. Cortisol-induced cell death, leakage of LDH, and caspase-3 activation were blocked by the glucocorticoid receptor antagonist Mifepristone (RU-486), suggesting that cell injury was cortisol-dependent. In addition, we studied the effect of zinc on the expression of antioxidant genes such as metallothionein A (MTA), metallothionein B (MTB), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) during cortisol-induced cell injury. MTA, MTB, GST, and G6PD mRNA levels increased after treatment with zinc or cortisol, separately or in combination. Higher mRNA levels of MTA, MTB, GST, and G6PD were detected when cells were treated with $100{\mu}M$ $ZnSO_4$ and $1{\mu}M$ cortisol in combination at the same time compared to treatment with zinc or cortisol separately. Cells treated with zinc showed increased intracellular free zinc concentrations, and this response was significantly enhanced in cells treated with cortisol and zinc. In conclusion, zinc treatment inhibited cortisol-induced cytotoxicity and apoptosis through indirect antioxidant action.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.697-708
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• 1999

Background : Leukotriene (LT) $C_4$, $D_4$, and $E_4$, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen-induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. Methods : Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin(OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum $LTC_4$ and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. Results : Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum $LTC_4$ levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field ($\times$400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). Conclusion : These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

• Journal of Ginseng Research
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• v.32 no.4
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• pp.341-346
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• 2008

In the present study, we assessed the effects of white ginseng and red ginseng extract on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of ginseng extracts was investigated using the Morris water maze and Y-maze test. Drug-induced amnesia was induced by treating animals with scopolamine (2 mg/kg, i.p.), an antagonist of muscarinic acetylcholine (ACh) receptor. Tacrine was used a positive control. Ginseng extract (200 mg/kg, p.o.), tacrine (10 mg/kg, p.o.) administration significantly reduced the escape latency during training in the Morris water maze (p<0.05). At the probe trial session, scopolamine significantly increased the escape latency on day 5 in comparison with control (p<0.01). The effect of ginseng extracts on spontaneous alternation in Y-maze was similar to that of scopolamine treated group. In addition, numbers of arm entries were similar in all experimental groups. Moreover, red ginseng extract significantly inhibited acetylcholinesterase activity in the cortex and serum (p<0.05). Brain ACh contents of ginseng extract treated groups increased more than that of scopolamine group, which did not show statistically significant. These results suggest that ginseng extract may be useful for the treatment of cognitive impairment.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.9-18
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• 1997

The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.

• Clinical and Experimental Reproductive Medicine
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• v.18 no.2
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• pp.133-142
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• 1991

This study was carried out to observe the change in uterine cyclic nucleotide level and the effect of PAF on cyclic nucleotides in uterine tissue in early pregnany in order to understand reciprocal relation ship between PAF and cyclic nucleotides in pregnancy in the rat. The test groups were injected intramuscularly with $1{\mu}g$ of PAF or 1.25mg of BN-52021 on day 0, 1, 2, 3, 4 and 5 of pregnancy. The level of cyclic nucleotide in removed uterine tissue was assayed by using cyclic nucleotides test kits. The results showed that the cyclic AMP content in uterine tissue of non-pregnant at pro-oestrus rat was $2.91{\pm}0.33$ pmol/mg protein which was lower than those of pregnant rat. The cyclic GMP content in uterine tissue of non-pregnant rat was $0.39{\pm}0.20$ pmol/mg pro-tein which was also lower than those of pregnant rats. The maximum level in cAMP was $5.92{\pm}1.72$ pmol/mg protein on day 3 and cGMP, $1.03{\pm}0.22$ pmol/mg protein on day 4. On each day of pregnancy, PAF induced the increased cAMP level ompared with that of intact rat. That was significant on day 0, 2 and 4 of pregnancy, p<0.05, on the other hand PAF receptor antagonist, BN-52021 ecreased cAMP level in uterine tisssue. PAF as well as BN-52021 had not an consistent effect on changes in cGMP level. These results suggest that cyclic nucleotide levels in uterine tissue ware increased during early pregnancy and PAF influences cAMP level in uterine rather than cGMP level during peri-implantation period, accordingly demonstrating a possible involvement of PAF in the regulation of implantation-related events through cAMP-mediated process.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.887-897
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• 2000

Background : Since the exact pathogenesis of sepsis-induced ARDS has not been elucidated, the mechanisms of enhanced neutrophilic respiratory burst were probed in endotoxin primed neutrophils associated with the roles of phospholipase A2(PLA2), platelet activating factor(PAF) and apoptosis. Methods : In isolated fresh human neutrophils, effects of the inhibition of PLA2 and PAF on the apoptosis were examined by the method of Annexin-FITC/dual PIflow cytometry. The roles of PLA2 and PAF on the neutrophilic respiratory burst were also examined by measuring oxidant generation in cytochrome-c reduction assay. Activities of the PLA2 and lysoPAF acetyltransferase (lysoPAF AT) of the neutrophils were determined to understand the effect of endotoxin on these enzymatic activities which may be related to the neutrophilic respiratory burst and apoptosis. In addition, the role roles of PLA2 and PAF in neutrophilic adhesion to bovine endothelial cells were examined in vitro by neutrophil adhesion assay. To investigate the effect of oxidants on pulmonary surfactant, cytochemical ultrastructural microscopy was performed. To inhibit PLA2 and PAF, non-specific PLA2 inhibitor mepacrine (100 nM) and WEB 2086 (100 nM) or ketotifen fumarate (10 ${\mu}g$/ml) were used respectively in all in vitro experimental sets. WEB 2086 is PAF receptor antagonist, and ketotifen fumarate is a lyso PAF AT inhibitor. Results: The mapacrine treatment, provided and the endotoxin (ETX) treatment, resulted in increased apoptosis of neutrophils (p<0.001) while treatments of WEB 2086 and ketotifen did not. The inhibition of PLA2 and PAF decreased (p<0.001) production of oxidants from PMA-stimulated neutrophils. While endotoxin increased the PLA2 activity of neutrophils (p<0.01), mepacrine supressed (p<0.001) the activity, provided after treatment of ETX. The lyso PAF actyltransferase activity (lyso PAF AT) increased (p<0.01) after treatment of ETX. In contrast, mepacrine, WEB 2086 and ketotifen showed a tendency of decreasing the activity after treatment of ETX. The treatment of ETX incresed (p<0.001) neutrophil adhesion to endothelial cells, which was reversed by inhibition of PLA2 and PAF (p<0.01). The binding of oxidants to pu1monary surfactant was identified histologically. Conclusions : The enhanced neutrophilic respiratory burst by ETX plays a pivotal role in the pathogenesis of ARDS in terms of oxidayive oxidative stress. Increased production of oxidants from neutrophils is mediated by the activations of PLA2 and lyso PAF AT.

• Journal of Life Science
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• v.24 no.2
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• pp.173-180
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• 2014

Estrogen can promote or inhibit cellular proliferation depending on tissue cell types and physiological condition and acts through the signal transduction pathways mediated primarily by estrogen receptors. This study examined the effects of fulvestrant (Ful), a well-known antagonist for the estrogen receptor, on the action of $17{\beta}$-estradiol (E2) with respect to the proliferation and apoptosis of Chinese hamster ovarian (CHO) cells. We used different concentrations of E2, Ful, and E2 plus Ful during different treatment durations. Treatment with 15-40 ${\mu}M$ E2 significantly inhibited proliferation in a time-dependent manner, although it had no influence in concentrations up to 1 ${\mu}M$. Interestingly, Ful at 10-40 ${\mu}M$ also inhibited cellular proliferation in both a concentration- and time-dependent manner. In addition, Ful enhanced rather than decreased the inhibitory effect on cellular proliferation by E2 in combined treatment for 10 days. Thus, Ful does not appear to have an antagonistic effect on estrogen's anti-proliferative action in CHO cells. In TUNEL assays to confirm DNA fragmentation by E2 and/or Ful, CHO cells treated with 20 ${\mu}M$ E2 showed a TUNEL-positive reaction in most DAPI-stained nuclei, and cells treated with either 40 ${\mu}M$ Ful or 40 ${\mu}M$ Ful plus 20 ${\mu}M$ E2 also exhibited a TUNEL-positive reaction but at a lower rate compared to the E2-treated cells. These results indicate that Ful does not have an antagonistic effect on estrogen's anti-proliferative action in CHO cells, suggesting that the anti-proliferative and apoptosis-related mechanism(s) through DNA fragmentation by E2 and Ful may be mediated by different signal transduction pathways.