• Journal of Yeungnam Medical Science
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• 제17권1호
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• pp.12-20
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• 2000

The memory of pain can be more damaging than its initial experience. Several factors arc related the directions of pain memory: current pain intensity, emotion, expectation of pain, and peak intensity of previous pain. The possible mechanisms behind the memory of pain are neuroplastic changes of nervous system via peripheral and central sensitization. Peripheral sensitization is induced by neurohumoral alterations at the site of injury and nearby. Biochemicals such as K+, prostaglandins, bradykinin, substance P, histamine and serotonin, increase transduction and produce continuous nociceptive input. Central sensitization takes place within the dorsal horn of spinal cord and amplifies the nociceptive input from the periphery. The mechanisms of central sensitization involve a variety of transmitters and postsynaptic mechanisms resulting from the activations of NMDA receptors by glutamate. and activation of NK-1 tachykinnin receptors by substance-P and neurokinnin. The clinical result of peripheral and central sensitization is hyperalgesia, allodynia, spontaneous pain, referred pain, or sympathetically maintained pain. These persistent sensory responses to noxious stimuli arc a form of memory. The hypothesis of preemptive analgesia is that analgesia administered before the painful stimulus will prevent or reduce subsequent pain and analgesic requirements in comparison to the identical analgesic intervention administered after the painful stimulus, by preventing or reducing the memory of pain in the nervous system. Conventionally, pain management was initiated following noxious stimuli such as surgery. More recently, however many have endorsed preemptive analgesia initiated before surgery. Treatments to control postsurgical pain are often best started before injury activates peripheral nociceptors and triggers central sensitization. Such preemption is not achieved solely by regional anesthesia and drug therapy but also requires behavioral interventions to decrease anxiety or stress. Although the benefit of preemptive analgesia may not be obvious in every circumstance, and in many cases may not sufficient to abolish central sensitization, it is an appropriate and human goal of clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10691-10695
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• 2015

Background: Association of angiotensin converting enzyme (ACE) gene polymorphisms with lung cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports an especially high rate of tobacco usage in a variety of ways of consumption, compared with the rest of the Indian population. Materials and Methods: We conducted a population based case control study in two major high risk region for lung cancer from Northeast India. A total of 151 consecutive lung cancer cases diagnosed histopathologically and equal numbers of controls were recruited with record of relevant sociodemographic information. Blood samples were collected and processed to identify ACE gene polymorphism. Results: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72; p=0.037) prevalence of the ACE II genotype was observed among lung cancer cases. Smoking was significantly associated with increased risk of lung cancer (OR=1.70, CI=1.02-2.81; p=0.041). An enhanced risk was also observed for interaction of ACE II genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) and chewing (OR=3.68, CI=1.22-11.13; p=0.021). Conclusions: The present study indicates significant association s of the ACE II genotype with lung cancer in high risk Northeast India.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.51-51
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• 2003

The medicinal plant Cimicifuga Racemosa (Black cohosh) has been used to treat many kinds of neuronal and menopausal symptoms, such as arthritis, menopausal depression, nerve pain, etc. Here, we examined the effect of Cimicifugoside (CF), one of triterpene glycosides which have been known as pharmacologically active ingredients of C. Racemosa, on nicotinic acetylcholine receptor (nAChR)-mediated catecholamine (CA) secretion in bovine adrenal chromaffin cell. Cimicifugoside inhibited calcium increase induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nAChR agonist with a half maximal inhibitory concentration (IC50) of 18${\pm}$2${\mu}$M. In contrast, cimicifugoside did not affect the calcium increases evoked by high K$\^$+/, veratridine, and bradykinin. The DMPP-induced sodium increase was also inhibited by cimicifugoside with IC50 of 2${\pm}$0.3${\mu}$M, suggesting that the activity of nAChRs is inhibited by cimicifugoside. Cimicifugoside did not effect on the KCl-induced secretion but markedly inhibited the DMPP-induced catecholamine secretion which was monitored by carbon-fiber amperometry in real time, and by high performance liquid chromatography (HPLC) through electrochemical detection. The results suggest that cimicifugoside selectively inhibits nAChR-mediated response in bovine chromaffin cells.

• Journal of Rheumatic Diseases
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• 제24권4호
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• pp.192-202
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• 2017

Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.425-434
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• 1997

Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the $Na^+$ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II $(>10^{-9}\;M)$ inhibited $Na^+$ uptake and increased $[Ca^{2+}]_i\;level$ in the PTCs. However, low concentrations of $(<10^{-11}\;ANG\;II)$ stimulated $Na^+$ uptake and did not affect $[Ca^{2+}]_i\;level$. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis$({/beta}-amino\;ethyl ether)-N,N,N'$, N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on $Na^+$ uptake. When ANG II and bradykinin (BK) were treated together, $Na^+$ uptake was further reduced $(88.47{\pm}1.98%\;of\;that\;of\;ANG\;II,\;81.85{\pm}1.84%\;of\;that\;of\;BK)$. In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of $Na^+$ uptake. Arachidonic acid reduced $Na^+$ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on $Na^+$ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine $(10^{-6}\;M)$ and AACOCF3 $(10^{-5}\;M)$ for 1 hr before the addition of $(<10^{-9}\;ANG\;II)$, the inhibitory effect of ANG II was reversed. In addition, econazole $(>10^{-6}\;M)$ blocked ANG II-induced inhibition of $Na^+$ uptake. In conclusion, the $[Ca^{2+}]_i$ (calcium-calmodulin-dependent kinase) and phospholipase $A_2\;(PLA_2)$ metabolites are involved in the inhibitory effects of ANG II on $Na^+$ uptake in the PTCs.

• 한국수산과학회지
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• 제26권4호
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• pp.321-329
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• 1993

수산자원의 기능특성 해명을 위한 연구의 일환으로 전통수산발효식품으로 널리 이용되고 있는 멸치젓갈에 함유되어 있는 angiotensin-I 전환효소저해물질을 추출하여 gel 여과에 의하여 분리된 획분들의 작용 및 특성에 대해서 살펴보았다. 그 결과를 요약하면 다음과 같다. 1. ACE 저해물질의 추출 조건을 검토하기 위하여 가장 높은 ACE 저해효과를 나타내는 숙성 60일차의 멸치젓갈을 ethanol 및 acetone의 농도를 각각 10, 25, 50 및 $80\%$로 하여 추출하였을 때 ethanol 농도가 $50\%$인 획분이 가장 우수한 저해효과를 나타내었다. 2. 멸치젓갈 숙성중 시료액의 $50\%$ ethanol 가용성 peptide-nitrogen 함량 및 ACE 저해효과는 아미노 질소 함량이 최고치에 달하는 숙성 60일차에 최대값을 나타내다가 그 후 다소 감소하는 경향을 나타내었다. 3. Gel 여과에 의한 멸치젓갈의 획분별 ACE 저해효과를 검토한 결과, 획분 C 및 D가 가장 높은 ACE 저해작용을 나타내어 이들을 rechromatography하여 분리한 단일 획분인 C'와 D'획분의 $IC_{50}$은 각각 97, $65{\mu}g$로 나타났다. 4. 분리한 단일 획분인 C'와 D'획분의 아미노산 조성은 다소 차이가 있었으며, C'획분은 threonine, glutamic acid 및 lysine의 함량이 많은 것으로 나타났으며, D'획분은 serine과 proline의 함량이 많은 것으로 나타났다.

• Tuberculosis and Respiratory Diseases
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• 제39권4호
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• pp.310-317
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• 1992

연구배경 : Angiotensin-converting enzyme (ACE)은 인체의 여러 조직 또는 혈청내에 존재하는 glycoprotein peptidyldipeptide hydrolase로써 여러 종류의 peptides에서 dipeptides를 떼어내는 역할을 담당한다. 이러한 ACE는 주로는 혈관 내피 세포에서 형성되며 인체에서는 폐에 가장 많은 모세혈관들이 존재하므로 ACE가 혈중에 존재하는 기질과 작용하는 곳 또한 폐의 모세 혈관내이다. 임상적으로 ACE는 유육종증의 진단 및 경과 관찰에 이용되며 기타 급성 또는 만성 폐질환에서 혈청 ACE 활성도가 감소된다는 사실이 보고되고 있다. 그러나 한 시점에서의 혈청 ACE 활성도는 폐손상의 유무 및 그 정도를 잘 반영한다고 볼 수는 없으나 시간 간격을 두고 차례대로 측정한 값은 예후와 관련이 있다고 알려져 있다. 이에 저자는 폐암환자를 대상으로 혈청내의 ACE 활성도를 측정하여 이들 환자에 있어서 향후 예후 예측의 지표로써의 가능성을 알아보고자 하였다. 방법 : 연구대상은 새로 진단된 폐암 환자로 하였고 대조군으로는 연구 대상군과 비슷한 연령군으로 하되 두군 모두에서 고혈압, 심장질환, 간질환, 신장 질환 그리고 폐암 이외의 기타 폐질환이 있는 사람은 제외시켰다. 연구대상군은 편평상피세포 폐암환자 19명, 선암폐암환자 13명, 소세포 폐암환자 9명 이었다. 결과 : 1) 편평상피세포 폐암환자의 혈청내 ACE 활성도는 $36.2{\pm}14.2$ U/L 이었고 선암 폐암환자는 $46.0{\pm}18.7$ U/L, 소세포 폐암환자는 $45.7{\pm}14.1$ U/L, 대조군은 $41.4{\pm}18.7$ U/L로 폐암환자의 ACE 활성도는 대조군과 차이가 없었으며 폐암의 세포형에 따라서도 차이가 없었고 폐암의 병기에 따라서도 ACE 활성도는 차이가 없었다. 2) 편평상피세포 폐암환자 4명과 선암 폐암환자 4명은 폐암의 치료로써 폐절제술을 받았으며 수술 전후 ACE 활성도는 편평세포 폐암환자가 수술전 $35.8{\pm}13.9$ U/L, 수술후 $12.5{\pm}3.9$ U/L로 의미있게 감소하였으며 선암 폐암환자에서는 각각 $47.1{\pm}5.9$ U/L, $15.0{\pm}3.9$ U/L로 수술후 의미있게 감소하였다. 3) 편평상피 세포 폐암환자중 3명과 선암 폐암환자 4명에 대하여 항암제를 투여받은 3개월에 걸쳐 측정한 ACE 활성도는 유의한 변화가 없었으며 임상적으로도 폐암의 호전은 없었다. 4) 소세포 폐암환자 9명은 3개월동안의 항암제 투여 중 임상적으로는 호전이 있었으나 혈청내 ACE 활성도는 의미있는 변화가 없었다. 결론 : 이상에서 폐정제술후 혈청내 ACE 활성도는 감소됨을 알 수 있었으나 폐암의 세포형, 병기, 임상적 호전과 혈청내 ACE 활성도는 연관이 없어 혈청 ACE 활성도는 폐암환자의 질병 경과 판정의 지표로써 부적합함을 알 수 있었다.