• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Microbiology and Biotechnology Letters
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• v.43 no.2
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• pp.112-119
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• 2015

The anti-inflammatory effect of Sargassum coreanum ethanolic extract (SCEE) was investigated using lipopolysaccharide (LPS)-induced inflammatory responses in this study. It was shown that there was no cytotoxicity in the viability of macrophages treated with SCEE when compared to the control. The production of NO was considerably suppressed by SCEE, approximately up to 50% at 100 μg/ml. This significantly decreased levels of IL-6, TNF-α, and IL-1β. In addition, the expression of iNOS, COX-2, NF-κB was suppressed by SCEE treatment. In in vivo testing, the croton oil-induced mouse ear edema was attenuated by SCEE and there were no mortalities in mice administered with 5000 mg/kg body weight of SCEE over a 2 week observation period. From these results, SCEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SCEE could be a potential agent for anti-inflammatory therapies.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.49-61
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• 1985

In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.382-395
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• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.110-117
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• 2017

The anti-inflammatory effect of Sargassum patens C. Agardh ethanol extract (SPEE) was examined based on the lipopolysaccharide (LPS)-induced inflammatory response in this study. SPEE treatment was not cytotoxic to macrophages compared to the control. The production of NO was suppressed by SPEE by approximately 28% at $100{\mu}g/ml$, and levels of interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ decreased in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ was suppressed by SPEE treatment. In vivo, croton oil-induced mouse ear edema was attenuated by SPEE and the infiltration of mast cells into the tissue decreased. Based on these results, SPEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SPEE is a potential agent for anti-inflammatory therapies.

• Korean journal of applied entomology
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• v.58 no.4
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• pp.321-327
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• 2019

When Aphidius colemani mummies were stored at four different temperatures (6, 8, 10 and 12 ± 1℃), they could be stored at 8℃ for 10 days with over 50% adult emergence. A number of mummies of Rhopalosiphum padi parasitized by A. colemani adults emerged from mummies after 8℃ storage clearly reduced with increasing duration of storage and especially declined with storage longer than 13 days showing < 20% parasitism. However, there were no differences in aphid parasitisms by A. colemani on 3 to 10 days after storage. Over 3 day storage at 8℃ was adversely affected on survival of A. colemani adults. Therefore, cold storage of A. colemani adults is considered as an unsuitable method for mass production of biological control agent. When 2-day-old Meteorus pulchricornis cocoons were stored at 6, 8 and 10 ± 1℃, it was possible to be stored up to 63 days at 8℃, showing the highest emergence. With increasing of cold storage duration at 8℃, parasitism on 2^nd and 3^rd larval instar of Spodoptera litura by stored M. pulchricornis significantly reduced. However, parasitic rate by M. pulchricornis stored for 2 weeks was similar to that by 1 week stored ones. Therefore, M. pulchricornis cocoons could be stored up to 2 weeks at 8℃ for stockpiling before release.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.1
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• pp.47-56
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• 2008

Risperidone is a widely prescribed atypical antipsychotic agent. Approved by the FDA as the first drug to treat irritability associated with autism in children, it is also used to treat tic disorder and Tourette's syndrome. Its adverse reactions related to dentistry include dry mouth, the mechanism of which is yet to be identified. The aim of this study is to identify, at the cellular level, how and to what extent risperidone affects intracellular free calcium concentration ($[Ca^{2+}]_i$), an primary intracellular factor in the regulation of fluid secretion in salivary gland cells. The human salivary gland cell line (HSG) was grown in MEM supplemented with 10% BCS. In order to measure $[Ca^{2+}]_i$, Fura-2/AM was loaded in the HSG, and fluorescence at 340 nm/380 nm excitation was measured in the 500 nm emission ratio. After every experiment, a calibration experiment was conducted in order to readjust the ratio to the actual $[Ca^{2+}]_i$. Changes in $[Ca^{2+}]_i$ were measured in the presence of carbachol, ATP and histamine. The researcher then explored how the pretreatment of risperidone affected such changes. Findings of this study include: 1. In HSG, $[Ca^{2+}]_i$ increased due to the addition of carbachol, ATP and histamine. The presence of risperidone inhibited the action of histamine on this process, while making little effect on that of carbachol and ATP. 2. A quantification of $[Ca^{2+}]_i$ in relation to histamine of different concentrations indicates that the effect of histamine was concentration dependent with an $EC_{50}$ of $3.3{\pm}0.5\;{\mu}M$. 3. The inhibitory effect of risperidone on histamine-induced $[Ca^{2+}]_i$ was concentration-dependent with an $IC_{50}$ of $104.4{\pm}14\;nM$. 4. Risperidone inhibits histamine-induced Ca2+ release from endoplasmic reticulum and influx of extracellular $Ca^{2+}$ in HSG cells(p<0.05).

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• Journal of Chest Surgery
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• v.33 no.3
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• pp.221-229
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• 2000

Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.