• The Korean Journal of Pain
• /
• 제25권1호
• /
• pp.7-15
• /
• 2012

Background: Neuropathic pain is a chronic pain due to disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Analgesic drugs combined can reduce pain intensity and side effects. Here, we studied the analgesic effect of nimesulide, nefopam, and morphine with different mechanisms of action alone and in combination with other drugs in chronic constriction injury (CCI) model of neuropathic pain. Methods: Male Wistar rats (n = 8) weighing 150-200 g were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. Nimesulide (1.25, 2.5, and 5 mg/kg), nefopam (10, 20, and 30 mg/kg), and morphine (1, 3, and 5 mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. In the combination strategy, a nonanalgesic dose of drugs was used in combination such as nefopam + morphine, nefopam + nimesulide, and nimesulide + morphine. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were, respectively, used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7,10, and 14 post injury. Results: Nefopam (30 mg/kg) and nimesulide (5 mg/kg) blocked mechanical and thermal allodynia; the analgesic effects of morphine (5 mg/kg) lasted for 7 days. Allodynia was completely inhibited in combination with nonanalgesic doses of nefopam (10 mg/kg), nimesulide (1.25 mg/kg), and morphine (3 mg/kg). Conclusions: It seems that analgesic drugs used in combination, could effectively reduce pain behavior with reduced adverse effects.

• Journal of Chest Surgery
• /
• 제38권4호
• /
• pp.263-270
• /
• 2005

최근 고령화 사회가 진행되어 가면서 폐암환자에서도 수술에 적응이 되지 않는 고령의 환자가 점차 증가하는 추세를 보이고 있어 독성이 적은 치료방법의 개발에 대한 필요성이 증가되고 있다. 따라서 기존의 항암제에 비하여 비교적 안정적으로 사용이 가능할 것으로 생각되는 선택적인 COX-2 억제제인 Nimesulide를 처치하여 COX-2 발현 유무와 COX-2 억제제가 비소세포폐암에 미치는 세포독성과의 상관관계를 연구하였다. 대상 및 방법: A549, H1299 비소세포폐암 세포주에서 COX-2 단백질에 대한 면역조직화학염 색을 시행하였으며, Nimesulide 처치후 XTT 분석, FACS 분석, Hoechst 33258 염색을 시행하였다. 결과: COX-2 단백질의 면역조직화학염색결과 A549 비소세포폐암 세포주는 COX-2 단백질에 강한 발현을 나타낸 반면, H1299 비소세포폐암 세포주는 발현을 나타내지 않았다. XTT 분석결과 Nimesulide의 A549, H1299 비소세포폐암 세포주에 대한 세포독성은 유사하였으며, Nimesulide의 $IC_{50}$은 A549 비소세포폐암 세포주에서는 $70.9 {\mu}M$이었으며, H1299 비소세포폐암 세포주에서는 $56.5 {\mu}M$이었다. FACS 분석에서는 각각의 세포군에서 $G_0/G_1$ 기에서 세포주기의 지연이 관찰되었으며, S기의 세포는 감소되었다. Hoechst 33258 염색에서는 양군에서 세포핵의 주변부 농축 현상 및 핵 분절을 가진 많은 사멸세포가 관찰되었다. 걸론: 선택적인 COX-2억제제인 Nimesulide는 비소세포폐암 세포주에서 암세포의 증식을 억제함을 알 수 있었으며, 암세포증식 억제의 기전은 세포자멸사의 유도와 $G_0/G_1$기에서 세포주기의 지연임을 알 수 있었으며, COX-2의 발현유무와 세포독성은 차이가 없는 것을 알 수 있었다. 따라서 Nimesulide와 같은 선택적인 COX-2 억제제는 다양한 항암제나 방사선치료와 병행하여 고위험군의 폐암환자에서 매우 효과적으로 사용될 수 있을 것으로 기대된다.

• Biomolecules & Therapeutics
• /
• 제12권4호
• /
• pp.221-227
• /
• 2004

Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.

• Biomolecules & Therapeutics
• /
• 제13권4호
• /
• pp.246-250
• /
• 2005

In this study, we tried to investigate whether diclofenac, acetaminophen, nimesulide, acetylsalicylic acid and tumor necrosis factor-alpha (TNF-alpha) significantly affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3H$-glucosamine for 24 hr and chased for 30 min or 24 hr in the presence of each agent to assess the effects on $^3H$-mucin release. The results were as follows: (1) TNF-alpha significantly increased mucin release from cultured HTSE cells during 24 hr of treatment period; (2) However, diclofenac, acetaminophen, nimesulide and acetylsalicylic acid did not affect mucin release, during 30 min of treatment period. Basically, this finding suggests that non-steroidal antiinflammatory drugs (NSAIDs) might not function as a mucoregulator in various inflammatory respiratory diseases showing mucus hypersecretion, although further studies are needed.

• 한국환경독성학회:학술대회논문집
• /
• 한국환경독성학회 2002년도 추계국제학술대회
• /
• pp.173-173
• /
• 2002

In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyp1a1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cyp1a1 mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. And Pretreatment of Aspirin, Celecoxib, Nimesulide and other several Cox-inhibitors in vitro, inhibited the TCDD stimulated EROD activity and Luciferase acitivity. In case of cyp1a1 mRNA level, Nimesulide and SB100 were able to decrease cyp1a1 mRNA that was stimulated by TCDD, but other tested COX-inhibitors were not decrease. We don't know this different result exactly. For the action of Cox-inhibitors on the Cyp1a1, it seems to be important to do pretreatment of these chemicals as apposed to TCDD. In this study, thus, we have suggested that COX-inhibitors such as aspirin, celecoxib, Nimesulide and other several Cox-inhibitors decrease the TCDD induced Cyp1a1.

• The Korean Journal of Pain
• /
• 제25권3호
• /
• pp.198-199
• /
• 2012

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.227.1-227.1
• /
• 2002

Cyclooxygenase (Cox-2) is involved in tumorigenesis. hence. considered to be a molecular target for chemoprevention and chemomodulation. Selective Cox-2 inhibitors including Celecoxib and Nimesulide have been studied for their anticancer activity when given alone and in combination with radiation or cytotoxic agents. In this study, we synthesized more than 140 analogues of Celecoxib and Nimesulide. and evaluated their inhibitory effects on Cox-l and Cox-2 activity as well as cytotoxicity in order to find promising anticancer agents having selective Cox-2 inhibitory effect. (omitted)

• Archives of Pharmacal Research
• /
• 제29권11호
• /
• pp.977-983
• /
• 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.

• Tuberculosis and Respiratory Diseases
• /
• 제48권2호
• /
• pp.191-202
• /
• 2000

목 적: 기관지 천식은 기도의 과민 반응을 특정으로 하는 기도 내 염증 질환이다. 최근 염증반응에 관여하는 cyclooxygease(COX) 에 대해 90년대 초 새로운 형태의 COX2가 발견되었다. 또한 최근 COX2만을 선택적으로 억제하는 약제가 개발되어 이에 대한 연구가 활발히 진행 중이다. 따라서 저자는 기도 내 염증 반응을 특징으로 하는 기관지 천식에서 COX2 발현 양상과 혈중 프로스타글란딘 E2를 측정하고 COX2 억제제를 사용한 후 COX2 발현, 프로스타글란딘 E2의 변화 및 기도 저항의 변화를 알아보았다. 대상 및 방법: 총 38마리의 Sprague-Dawley 백서(250-300g)를 대상으로 정상 대조군, 천식 대조군, 치료군의 3군으로 나누어 실험하였다. 각 세 군에 대해 제 28 연구일에 즉시형 기관지 수축 반응을 유발시킨 후 기도 저항을 측정하였다. 제 30연구일에 혈장 내 프로스타글란딘 E2 수치를 측정하고 기도 및 폐 실질 내 호산구 침윤 정도 및 COX2 면역 조직 화학 염색에 대한 발색 정도를 image analysis를 통해 확인하였다. 결 과: 기관지 및 폐 실질 내 호산구 침윤은 천식 대조군과 치료군의 두 군간에 통계적으로 유의한 차이가 없었다. COX2 면역 조직 화학 염색 및 혈중 프로스타글란딘 E2 농도에 있어서 정상 대조군, 천식 대조군, 치료군의 세 군에서 통계적으로 유의한 차이가 없었다. 치료군에서 nemesulide 투여 후 OVA으로 즉시형 기관지 수축 반응을 일으킨 상태에서 측정한 기도 저항은 nemesulid를 투여하기 전과 비교해서 통계적으로 유의한 차이가 없었다. 결 론: 결론적으로 COX2는 알레르겐 유발성 천식의 병태 생리에 있어서 주된 경로가 아니며 향후 천식 모델에서 COX2 억제제를 사용한 후 lipoxygenase 의한 대사산물과의 상관 관계와 COX2 억제제의 투여하는 방법에 있어서 투여 용량 또는 투여 횟수를 달리하거나 COX2에 대한 선택성이 더 높은 약제를 투여한 후 기도 내 COX2의 변화에 대한 연구가 필요하리라 사료된다.

• BMB Reports
• /
• 제36권1호
• /
• pp.82-94
• /
• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.