• Journal of Preventive Medicine and Public Health
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• 제35권3호
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• pp.245-254
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• 2002

노인에서 $H_2$-RA의 복용과 위암간의 관련성을 밝히기 위한 코호트 내 환자-대조군 연구를 수행하였다. 연구 모집단은 공무원 및 사립학교 교직원을 대상으로 하는 의료보험 관리공단의 피보험자 및 피부양자로서 부산지역에 거주하는 65세 이상의 노인들을 대상으로 구축된 한국노인약물역학코호트의 구성원 중에서 교란변수에 대한 정보 획득을 위해 실시한 설문조사에서 응답한 사람들로 구성된 코호트이었다. $H_2$-RA폭로군은 1993년 1월 1일부터 1994년 12월 31일 사이에 코호트 대상자들이 병원에서 약물을 처방 받아 청구한 자료를 바탕으로 구축한 약물처방 데이터베이스에서 1회 이상 $H_2$-RA를 처방 받은 사람들도 정의하였다. 환자군 76명은 코호트의 위암 환자 확진을 위한 병원방문 조사 자료, 중앙 암등록 자료, 부산 지역 암등록 자료를 이용하여 확인되었다. 대조군은 환자군 확인방법과 동일한 방법을 이용하여 확인하였을 때 암으로 진단받은 병력이 없는 코호트 대상자들 중에서 환자군의 출생 년도와 성별에 따라 1:4의 비율로 개별 짝짓기를 실시하여 뽑은 304명이었다. 잠재적 인 교란변수에 대한 정보는 설문조사를 통해 수집하였다. 조건부 로지스틱 회귀모델을 이용하여 교란변수의 영향을 통제한 상태에서 구한 $H_2$-RA 복용과 위암 발생간의 관련성을 대응비와 95% 신뢰구간으로 제시하였다. 그 결과, 위궤양 증상 여부, 약물 복용력, 체질량 지수의 영향을 통제한 상태에서 $H_2$-RA의 복용은 위암 발생의 위험을 4.6배 증가시키는 것으로 관찰되었다. $H_2$-RA를 7일 이내로 사용한 군은 $H_2$-RA를 사용하지 않은 군에 비해 위암 발생의 위험이 4.6배 증가하는 것으로 관찰되었고 7일 이상 사용한 군은 2.3배 증가하는 것으로 관찰되었다. 투여 경로별로 나누어 보았을 때에는 경구로 투여한 경우에서 유의한 위험 수준의 상승을 관찰하지 못한 반면에 주사로 투여한 경우에서 위험이 4.4배 증가하는 것으로 관찰되었고, 주사와 경구의 두 가지 경로 모두로 $H_2$-RA를 투여 받은 경우 그 위험은 더욱 상승하는 것으로 관찰되었다.시메티딘, 라니티딘, 파모티딘 등의 개별 성분명 별로 위암 발생의 위험에 대한 차이는 관찰되지 않았다. 결론적으로 $H_2$-RA를 사용한 노인에서 사용하지 않은 노인에서 비해 위암 발생의 위험이 더 높아진다는 결론을 얻었으며, 이는 $H_2$-RA투여로 인해 위내에 발생한 무위산증(achlorhydria)이 위암 발생의 위험을 높일 것이라는 기존의 가설을 뒷받침하는 결론이라고 할 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3851-3854
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• 2013

• The Korean Journal of Pain
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• 제32권1호
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• pp.3-11
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• 2019

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

• The Korean Journal of Pain
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• 제34권1호
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• pp.35-46
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• 2021

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 ㎍/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.

• Clinical and Experimental Reproductive Medicine
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• 제30권4호
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• pp.269-280
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• 2003

Objective: We reported the overcoming effect of $Ni^{2+}$ on the in vitro 2-cell block of mouse embryos. In this study, we aim to investigate whether $Ni^{2+}$ should induce intracellular $Ca^{2+}$ transient in the mouse embryos. Materials and Methods: Embryos were collected at post hCG 32hr from the oviduct of the ICR mouse and cultured in M2 medium omitted phenol red. Intracellular $Ca^{2+}$ was checked by using a confocal laser scanning microscope and fluo-3AM by using various intracellular $Ca^{2+}$ antagonists. Results: In 1mM $Ni^{2+}$ treated medium which contained $Ca^{2+}$(1.71mM), 75.7% of the embryos showed $[Ca^{2+}]i$ transient about 200 sec later. In the $Ca^{2+}$-free medium, 69.8% of the embryos showed $[Ca^{2+}]i$ transient. In U73122, phospholipaseC(PLC) inhibitor (5uM, 10min) pretreated group, 33.3% of the embryos showed $[Ca^{2+}]i$ transient. Heparine, inositol 1, 4, 5-triphosphate receptor(IP3R) antagonist preinjected embryos showed no response with 1mM $Ni^{2+}$. In danthrolene treatment, ryanodine receptor(RyR)-antagonist, 43% embryos showed $[Ca^{2+}]i$ transient but they showed delayed response about 340sec in the presence of $Ca^{2+}$. Conclusions: Summing up the above results, $Ni^{2+}$ seems to induce $Ca^{2+}$-release from the $Ca^{2+}$-store even in the $Ca^{2+}$-free medium. IP3 receptors of the mouse 2-cell embryos might have an essential role for the intracellular $Ca^{2+}$ increase by $Ni^{2+}$.

• Journal of Ginseng Research
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• 제39권1호
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• pp.69-75
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• 2015

Background: Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-${\beta}$ signaling. Methods: Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to $H_2O_2$. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined byWestern blot analysis. The roles of ER-${\beta}$, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists. Results: Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-${\beta}$, PI3K, and p-Akt expression. Conversely, ER-${\beta}$ inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression. Conclusion: Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-${\beta}$ expression.

• 한국식품영양학회지
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• 제30권6호
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• pp.1364-1369
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• 2017

There is a growing demand for natural sleep aids due to various side effects of long-term administration of pharmacological treatments for insomnia. Honey has been reported to exhibit numerous potential health benefits, and it is hypothesized that honey may favorably affect insomnia treatment. Therefore, this study was performed to investigate the possible hypnotic effect of clover honey (CH) and to determine its in vivo mechanism. The total flavonoid content (TFC) of CH and fractions extracted with ethylacetate (EtOAc) and $H_2O$ was measured. The pentobarbital-induced sleep test using $GABA_A$-benzodiazepine (BZD) agonists and antagonists was conducted to evaluate the potential mechanism of action behind the sedative-hypnotic activity of CH in mice. The results showed that administration of 500 and 1,000 mg/kg of CH significantly (p<0.01) reduced the sleep latency to a level similar to that of diazepam (DZP, 2 mg/kg), and 1,000 mg/kg of CH significantly (p<0.01) prolonged the sleep duration, which was comparable to that of DZP (2 mg/kg). Administration of the EtOAc fraction with a higher TFC significantly reduced the sleep latency at 50 to 200 mg/kg and prolonged the sleep duration at 100 to 200 mg/kg, which were comparable to those after administration of DZP (2 mg/kg). However, co-administration of CH and EtOAc with flumazenil, a specific $GABA_A-BZD$ receptor antagonist, blocked the hypnotic effect. Our findings suggest that the hypnotic activity of CH may be attributed to allosteric modulation of $GABA_A-BZD$ receptors. The TFC of CH is expected to be a key factor that contributes to its hypnotic effect.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.493-501
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• 1998

The most significant direct role of estrogen in vivo is its ability to elicit receptor-mediated cellular proliferation in mammalian target tissues. However, the mechanism by which exogenously added estrogen causes the neoplastic transformation of renal cortical cells is yet to be uncovered. The present study was designed to evaluate interaction of $17{\beta}-estradiol\;(E_2)$ with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on proliferation and $P_i$ uptake in primary cultured rabbit renal proximal tubular cells in phenol red-free, hormonally defined-medium. $[^3H]-thymidine$ incorporation increased markedly by about 133% and 141% more in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$, respectively, than that of control. Cell count was 162% and 143% greater in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$ , respectively, compared with control. Among all time points examined, there was an increase in $[^3H]-thymidine$ incorporation in the presence of $10^{-9}\;M\;E_2$ at day 9 or 13, respectively. However, $E_2$ ($10^{-9}\;M$) significantly drove up cell count to 160% of that of control at day 13, while it had a slight but statistically insignificant effect at day 9. $E_2-induced$ stimulation of $[^3H]-thymidine$ incorporation was completely reversed by $E_2$ antagonists (progesterone or tamoxifen). $E_2$ ($10^{-9}\;M$) or EGF ($10^{-8}\;M$) significantly stimulated $[^3H]-thymidine$ incorporation by 144% and 154% of control. $E_2$ plus EGF was synergistic on $[^3H]-thymidine$ incorporation (204% of control), while $E_2$ plus IGF-I showed a slight but no significant synergistic effect. Cell number also displayed similar pattern. $E_2$ ($10^{-9}\;M$) significantly stimulated $P_i$ uptake to 134% of control. $E_2$-induced stimulation of $P_i$ uptake was partially reversed by $E_2$ antagonists. EGF or IGF-I ($10^{-8}\;M$) significantly also increased $P_i$ uptake to 132% or 129% of control. $E_2$ plus EGF had synergistic effect on $P_i$ uptake, while $E_2$ plus IGF-I did not. In conclusion, $E_2$ may act not only directly interaction with its receptors but also indirectly as a modulator of EGF in proliferation and $P_i$ uptake of primary cultured rabbit renal proximal tubular cells.

• 대한기관식도과학회지
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• 제10권2호
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• pp.22-27
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• 2004

Background : LPRD(Laryngopharyngeal reflux disease) gives rise to inflammatory change in the pharyngolaryngeal tissue with various otolaryngologic symptoms. Ranitidine, histamine H2receptor antagonists, are currently used as therapeutic medications. However, the efficacy of Ranitidine on LPRD has not been proven yet. Objectives : We intended to analyze the efficacy of the Ranitidine on LPRD. Materials :md Methods : In 20 multicenter, 607 patients with LPR(laryngopharyngeal reflux) symptom were observed to evaluate their symptoms and laryngoscopic findings after 4 weeks, 8 weeks, and 12 weeks of treatment of Ranitidine. Results : The symptom of LPR including globus sensation, sore throat hoarseness, regurgitatioin are improved after 4 weeks $86.2\%,\;8 weeks\;91.5\%,\;12 weeks\;92.9\%$ of Ranitidine treatment and improved after 4 weeks $91.5\%,\;8 weeks\;94.5\%,\;12 weeks\; 97.2\%$ of Ranitidine combined with prokinetics. The rates of sore throat, chronic cough, globus sensation improvement at 8 weeks after treatment are $26.7\%,\;16.7\%,\;16\%$. Conclusion : In patient with LPR, Ranitidine treatment reduces LPR symptoms very effectively.

• Molecules and Cells
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• 제22권1호
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• pp.44-50
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• 2006

We investigated the possible role of p38 MAPK and $ET_B$ receptors in ET-1 induction of cyclooxygenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) in cultured feline esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated with 10 nM ET-1 and expression of COX-1 and COX-2, involvement of receptors, and activation of p38 MAPK, were examined by Western blot analysis. Levels of $PGE_2$ induced by ET-1 were measured by Elisa. Using $ET_A$and $ET_B$ antagonists (BQ-123 and BQ-788, respectively), the contribution of the ET receptors to COX-1 and COX-2 expression induced by ET-1 was determined. Western blot analysis revealed that treatment of ESMC with ET-1 resulted in transient expression of COX-2 and activation of p38 MAPK. Activation of p38 MAPK was maximal after 1 h. SB202190, a p38 MAPK inhibitor, reduced expression of COX-2, but not COX-1. ET-1-induced release of $PGE_2$ was also blocked by SB202190. COX-2 expression was upregulated only via the $ET_B$ receptor, and COX-1 expression was not affected by either antagonist. Taken together, our data suggest that ET-1 causes p38 MAPK-dependent expression of COX-2 by interacting with $ET_B$ receptors on ESMC.