• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.352-361
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• 2021

Objective: The study assessed the developmental potential of germinal vesicle (GV) oocytes subjected to in vitro maturation (IVM) after prematuration culture with cilostamide (a phosphodiesterase-3 inhibitor) and the impact of cilostamide exposure on the morphology of meiosis II (MII) oocytes and subsequent embryo quality. Methods: In total, 994 oocytes were collected from 63 patients. Among 307 GV oocytes, 140 oocytes were selected for the experimental group and 130 oocytes for the control group. The denuded GV-stage oocytes were cultured for 6 hours with cilostamide in the experimental group and without cilostamide in the control group. After 6 hours, the oocytes in the experimental group were washed and transferred to fresh IVM medium. The maturational status of the oocytes in both groups was examined at 26, 36, and 48 hours. Fertilization was assessed at 18 hours post-intracytoplasmic sperm injection. Embryo quality was assessed on days 3 and 5. Results: In total, 92.1% of the oocytes remained in the GV stage, while 6.4% converted to the MI stage (p<0.01) after cilostamide exposure. In both groups, more MII oocytes were observed at 36 hours (25.8% vs. 21.5%) than at 26 hours (10.8% vs. 14.6%) and 48 hours (13% vs. 7.9%) (p>0.05). With the advent of cilostamide, blastocyst quality was better in the experimental group than in the control group (p<0.05). Conclusion: Cilostamide effectively blocked nuclear maturation and promoted cytoplasmic growth. Prematuration culture with cilostamide enabled synchronization between cytoplasmic and nuclear maturity, resulting in better blastocyst outcomes.

• The Korean Journal of Pain
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• v.23 no.4
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• pp.236-241
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• 2010

Background: Selective inhibitors of cycloosygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antionociception of selective COX-2 inhibitor. Methods: To examine the antionociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are ${\mu}$, $\delta$, and k opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2 Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test, CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1, Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The $\delta$ and $\kappa$ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the ${\mu}$ opioid receptor is related only to facilitated pain.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.977-983
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• 2006

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.83-89
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• 1998

Ginseng total saponins (GTS) injected intracerebroventricularly (i.c.v.) at doses from 0.1-1 vs inhibited the i.c.v. injection stress-induced plasma corticosterone levels in mice. The inhibitory action of GTS was blocked by co-administered NG-nitro-L-arginine methyl ester (L-NAME; 1.5 us, i.c.v.), an. inhibitor of nitric oxide synthase (NOS). Of the ginsenosides Rbl, Rba, Rc, Rd, Re, Rf, Rgl,20(S)-Rg3, and 20(R)-Rg3 injected i.c.v. at doses from 0.01 to 0.3ug(or 1 uE),20(5)-Rg3 and Rc significantly inhibited the o.c.v. injection stress-induced Plasma corticosterone levels. The inhibitory actions of 20(S)-Rg3 and Rc were blocked by co-administered L-NAME (1.5 n, i.c.v.). These results suggest that G75, 20(S)-Rg3 and Rc may inhibit the i.c.v. injection stress-induced hypothalamo-pituitary-adrenal response by inducing NO production in the brain.

• Journal of Ocean Engineering and Technology
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• v.34 no.5
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• pp.342-350
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• 2020

In this study, a hydrate inhibition system is investigated for shallow water gas fields. Mono-ethylene glycol (MEG) injection has been used as a typical method for inhibiting hydrate formation in gas fields; therefore, most offshore platforms are equipped with MEG injection and regeneration processes. A recent application of a kinetic hydrate inhibitor (KHI) has reduced the total volume of MEG injection and hence reduce the operating cost. Experiments are designed and performed to evaluate and verify the KHI performance for inhibiting hydrate formation under shallow water conditions. However, the shut-in and restart operation may require the injection and regeneration of MEG. For this operation, the MEG concentration must be optimized while considering the cost of MEG regeneration. The obtained results suggest that decreasing MEG concentration from 80 wt% to 70 wt% can reduce the life cycle cost (LCC) of MEG regeneration process by approximately 5.98 million USD owing to reduced distillation column cost. These results suggest that the hydrate inhibition system must be evaluated through well-designed experiments and process simulations involving LCC analysis.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.233-239
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• 1995

To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.93-98
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• 2001

The precise mechanism of set-point regulation in hypothalamus was not elucidated. Nitric oxide synthases(NOS) were detected in hypothalamus, however, the roles of NO in hypothalamus was not fully studied. So, we tested the effects of NO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. NO donor sodium nitroprusside (SNP, 4 nmol, i.c.v.) elicited marked febrile response, and this febrile response was completely blocked by indomethacin (a cyclooxygenase inhibitor). But, ODQ (selective guanylate cyclase inhibitor, $50\;{\mu}g,$ i.c.v.) did not inhibit fever induced by SNP. The cyclic GMP analogue dibutyryl-cGMP $(100\;{\mu}g,\;i.c.v.)$ induced significant pyreses, which is blocked by indomethacin. $N^G-nitro-L-arginine$ methyl ester (L-NAME, non selective NOS inhibitor) inhibited fever induced by $interleukin-1{\beta}\;(IL-1{\bata},\;10\;ng,\;i.c.v.),$ one of endogenous pyrogens. These results indicate that NO may have an important role, not related to stimulation of soluble guanylate cyclase, in the signal pathway of thermoregulation in hypothalamus.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.501-509
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• 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Suppression of MAPKs and NF-κB is implicated as a vital mechanism of action of several traditional Chinese medicines for AD therapy. Although overexpression of MAPK mRNA in the skin tissue has been shown in the AD model, the roles of each MAPK in AD pathogenesis have rarely been studied. This study examined the effect of NJK14047, an inhibitor of p38 MAPKs, on AD-like skin lesions induced in BALB/c mice by sensitization and challenges with 1-chloro-2,4-dinitrobenzene (CDNB) on dorsal skin and ears, respectively. After induction of AD, NJK14047 (2.5 mg/kg) or dexamethasone (10 mg/kg) was administrated for 3 weeks via intraperitoneal injection. Following its administration, NJK14047 suppressed CDNB-induced AD-like symptoms such as skin hypertrophy and suppressed mast cell infiltration into the skin lesions. It also reduced CDNB-induced increase in T_H2 cytokine (IL-13) and T_H1 cytokines (interferon-γ and IL-12A) levels but did not decrease serum IgE level. Furthermore, NJK14047 blocked CDNB-induced lymph node enlargement. These results suggest that NJK14047, a p38 MAPK inhibitor, might be an optimal therapeutic option with unique modes of action for AD treatment.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.130.3-131
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• 2003

The biological effects of NADPH-dependent isocitrate dehydrogenase (IDPc) inhibitor. DA-11004, was examined in obese zucker rats or streptozotocin-induced diabetic SD rats. Diabetes was induced by injection of streptozotocin (50mg/kg) dissolved in citrate buffer (pH 4.8) into the tail vein and induction of diabetes was confirmed by the measurement of the tail blood glucose level at 48h. DA-11004 (30mg/kg, po) was injected for successive 7days and significantly reduced the plasma glucose in streptozotocin-induced diabetic rats (P<0.05). (omitted)

• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.153-169
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT, Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT+YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.