• Clinical and Experimental Reproductive Medicine
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• 제37권1호
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• pp.41-48
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• 2010

목 적: 체외수정시술 시 황체기 보강은 근주, 경질, 경구 등의 다양한 방법으로 이루어지고 있는데, 경구 투여법은 환자의 순응도가 높고 비교적 안전한 방법이다. 본 연구에서는 황체기 보강을 근주로 시작하여 경구 투여로 전환하는 방법의 효용성과 전환 시기에 따른 결과를 비교 분석하고자 하였다. 연구방법: 2003년 9월부터 2009년 6월까지 분당서울대학교병원에서 체외수정시술을 시행받은 환자에서 배아 이식 후 태아 심박동까지 확인된 76주기를 대상으로 하였다. 과배란유도는 GnRH agonist long protocol (n=7) 또는 GnRH antagonist protocol (n=66)을 이용하였으며 3주기에서는 냉동배아 이식을 시행하였다. 황체기 보강을 위하여 난자 채취일부터 매일 progest in oil 50 mg을 근주하였고, 태아 심박동이 확인된 후 임신 6~7주 (n=17) 또는 8주 이후 (n=59)에 micronized progesterone (Utrogestan, Laboratoires Besins International, France) 300 mg을 매일 경구로 투여하였다. 결 과: 대상군 전체의 유산율은 3.9% (3/76)이었으며, 경구 투여 전환시의 임신 주수는 평균 8주 4일 (난자 채취일로부터 $46{\pm}5.8$일)이었다. 황체기 보강을 임신 6~7주 사이에 경구 투여로 전환한 17주기 중에서 1례의 자연유산이 확인되었으며 유산 시 주수는 9주 4일이었다. 8주 이후에 경구 투여로 전환한 59주기 중에서는 2례의 자연유산이 확인되었으며 (11주 3일, 11주 4일), 두 군의 자연유산율은 각각 5.6%와 3.4%로 두 군 간에 통계적으로 유의한 차이는 없었다 (p=0.678). 결 론: 체외수정시술 후 황체기 보강을 시행하는 경우 태아 심박동이 확인된 이후에 근주 투여를 경구 투여로 전환하는 방법은 비교적 낮은 유산율을 보임을 확인하였으며, 특히 8주 이전에 전환하는 것도 유용한 방법이라 사료된다.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.570-576
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• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.382-395
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• 1992

GABA는 중추신경계의 대표적인 신경전달 물질로서 $GABA_A$수용체 또는 $GABA_B$수용체에 작용하여 진정 작용, 항 불안 작용, 및 근이완 작용을 하는 것으로 알려져 있다. 근래에는 말초조직에도 GABA가 존재하며 신경조정인자 혹은 신경전달인자로서 작용한다는 보고가 있다. 정관에 대한 자율신경 지배는 아드레날린성, 콜린성과 비콜린성 비아드레날린성 신경섬유들이 분포하고 있으나, 종 혹은 부위에 따라 이들 구성요소들의 수축성에 대한기여도가 다른 것으로 알려져 있다. 본 실험에서는 흰쥐의 전립선 부위 정관의 기본장력 및 전기장 유발 수축에 대한 교감 신경성, 부교감 신경성 및 퓨린성 효현제의 영향을 관찰하였으며, 정관의 흥분성 약물 및 전기장 유발 수축에 미치는 GABA 및 GABA 관련 약물의 영향을 관찰함으로서 정관의 수축운동에 대한 GABA의 작용기전을 규명해 보고자 흰쥐(Sprague-Dawley)의 전립선 부위 정관 절편을 적출 근편 실조에 현수하고, 등척성 장력을 측정하여 다음과 같은 결과를 얻었다. 1. GABA, muscimol 및 baclofen은 전기장자극(0.2 Hz, 1 msec, 80 V) 유발 수축을 농도 의존적으로 억제하였으며 그 효력은 GABA, baclofen 그리고 muscimol 순이었다. 2. GABA의 억제작용은 $GABA_B$ 수용체 길항제인 DAVA에 의하여 길항되었으나, $GABA_A$ 수용체 길항제인 bicuculline에 의해서는 길항되지 않았다. 3. Baclofen의 억제작용은 DAVA에 의하여 길항되었으나 muscimol의 억제작용은 bicuculline에 의해서는 길항되지 않았다. 4. Norepinephrine과 ATP는 농도 의존적으로 정관의 수축력을 증가 시켰으나 acetylcholine은 영향을 미치지 못하였다. 5. GABA, baclofen 및 muscimol은 정관의 기본 장력에는 영향을 미치지 않았으며, GABA는 norepinephrine과 ATP 유발 수축에는 영향을 주지 못하였다. 6. 적출 정관을 20초간 전기장 자극을 가하였을 때 ATP 수용체 탈감작제인 mATP를 전처치한 경우에는 FPC가 감소되었고, 신경원에서 catecholamine을 고갈시키는 reserpine을 전처치한 경우에는 STC가 감소되었다. 7. GABA는 mATP를 전처치한 군에서는 정관의 전기장 유발 수축에 영향을 주지 못하였으나, reserpine을 전처치한 군에서는 전기장 유발 수축을 억제하였다. 이상의 결과로 보아 흰쥐정관의 전립선 부위에는 아드레날린성 신경전달기전과 퓨린성 신경전달기전이 동시에 작용하고 있으며, GABA는 주로 신경원의 $GABA_B$ 수용체를 통하여 ATP의 유리를 억제하는 것으로 사료된다.

• The Korean Journal of Pain
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• 제23권3호
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• pp.179-185
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• 2010

Background: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats. Methods: Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated. Results: Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle. Conclusions: Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

• Clinical and Experimental Reproductive Medicine
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• 제24권1호
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• pp.143-151
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• 1997

The present study was designed to investigate if antithyroid antibodies (ATA) could affect the pregnancy outcome in euthyroid women undergoing in vitro fertilization and embryo transfer (IVF-ET). From October 1995 to September 1996, 28 euthyroid women with ATA who underwent IVF-ET were studied. Fifty-one euthyroid women without ATA who underwent IVF-ET served as control. Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody (TGA) were assayed using radio ligand assay kits as ATA. All patients included in study and control groups had only tubal factor in infertility. Long protocol of gonadotropin-releasing hormone agonist (GnRH-a) was used for controlled ovarian hyperstimulation (COH) in all patients. There were no significant differences between study and control groups in patient characteristics such as age, infertility duration and hormonal profile. There were also no significant differences between two groups with respect to the clinical response to COH and IVF results such as number of retrieved oocytes, fertilization rate, number of embryos frozen and number of embryos transfered. There were no correlations between ATA (TPOA and TGA) titers and fertilization rate. The clinical pregnancy rate per cycle seemed to be lower in the study group than in the control group (26.3% vs 39.3%), but the difference was not statistically significant. The biochemical pregnancy rate per cycle and miscarriage rate were significantly higher in the study group at 18.4% (7/38) and 40.0% (4/10) compared with 5.6% (5/89) and 11.4% (4/35) in the control group. In the study group, both TPOA and TGA titers were significantly higher in the biochemical pregnancy group than in the clinical pregnancy group or non-pregnancy group. In 10 women with ATA who achieved pregnancy following IVF-ET, both TPOA and TGA titers were significantly higher in the miscarriage group than in the ongoing or delivery group. In conclusion, euthyroid women with ATA appear to represent a less favorable subset within other tubal factor patients when treated with IVF-ET.

• Molecules and Cells
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• 제21권3호
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• pp.337-342
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• 2006

Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-$1{\mu}M$) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the $VIP_1$ agonist and found that it had no effect on pacemaker potentials. Pretreatment with $VIP_1$ antagonist ($1{\mu}M$) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one (ODQ, $100{\mu}M$), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 ($1{\mu}M$) or RP-8-CPT-cGMPS ($10{\mu}M$), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, $100{\mu}M$), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.146-146
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• 1998

The present study was designed to examine the effect of total ginseng saponin on contractile responses of vasoconstrictors in the rat aorta. Phenylephrine (an adrenergic ${\alpha}$$_1$-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in the rat aorta, respectively. However, in the presence of total ginseng saponin (600 $\mu\textrm{g}$/$m\ell$), the contractile responses of phenylephrine (10$\^$-5/ and 10$\^$-7/ M) and high potassium (3.5 ${\times}$ 10$\^$-2/ and 5.6 ${\times}$ 10$\^$-2/ M) were markedly potentiated whereas prostaglandin F$\sub$2${\alpha}$/ (5 ${\times}$ 10$\^$-6/ M)-induced contractile response was not affected. The contractile responses induced by phenylephrine (10$\^$-5/ M) and high potassium (3.5 ${\times}$ 10$\^$-2/ M) even in the presence of total ginseng saponin (600 $\mu\textrm{g}$/$m\ell$) were greatly inhibited by the pretreatment of nicardipine (10$\^$-6/ M), a calcium channel blocker. Taken together, these experimental results suggest that total ginseng saponin can enhance the contractile responses evoked by stimulation of adrenergic ${\alpha}$$_1$-receptor and the membrane depolarization in the rat aorta, which seems to be associated to calcium influx.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.171-177
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• 2011

Tonic smooth muscle exhibit the latch phenomenon: high force at low myosin regulatory light chains (MRLC) phosphorylation, shortening velocity (Vo), and energy consumption. However, the kinetics of MRLC phosphorylation and cellular activation in phasic smooth muscle are unknown. The present study was to determine whether $Ca^{2+}$-stimulated MRLC phosphorylation could suffice to explain the agonist- or high $K^+$-induced contraction in a fast, phasic smooth muscle. We measured myoplasmic [$Ca^{2+}$], MRLC phosphorylation, half-time after step-shortening (a measure of Vo) and contractile stress in rabbit urinary bladder strips. High $K^+$-induced contractions were phasic at both $22^{\circ}C$ and $37^{\circ}C$: myoplasmic [$Ca^{2+}$], MRLC phosphorylation, 1/half-time, and contractile stress increased transiently and then all decreased to intermediate values. Carbachol (CCh)-induced contractions exhibited latch at $37^{\circ}C$: stress was maintained at high levels despite decreasing myoplasmic [$Ca^{2+}$], MRLC phosphorylation, and 1/half-time. At $22^{\circ}C$ CCh induced sustained elevations in all parameters. 1/half-time depended on both myoplasmic [$Ca^{2+}$] and MRLC phosphorylation. The steady-state dependence of stress on MRLC phosphorylation was very steep at $37^{\circ}C$ in the CCh- or $K^+$-depolarized tissue and reduced temperature flattend the dependence of stress on MRLC phosphorylation compared to $37^{\circ}C$. These data suggest that phasic smooth muscle also exhibits latch behavior and latch is less prominent at lower temperature.

• International Journal of Oral Biology
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• 제46권4호
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• Toxicological Research
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• 제23권2호
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.