尼美舒利联合顺铂对肺癌细胞增殖与凋亡的影响及其机制探讨

目的 研究选择性环氧合酶-2(COX-2)抑制剂尼美舒利(NIM)单独以及与顺铂联合对肺癌A549细胞裸鼠移植瘤生长、Ki67及Caspase-3表达的影响,并进一步探讨其机制.方法 将裸鼠用统计学中的依体重按随机数字表法分为4组:对照组、尼美舒利组、顺铂组和联合用药组(尼美舒利+顺铂).将肺腺癌A549细胞接种至裸鼠皮下,并给予相应的药物治疗21d,观察移植瘤生长情况.免疫组化法检测Caspase-3及Ki67的表达变化.结果 尼美舒利联合顺铂对肺癌裸鼠移植瘤的生长抑制作用较单独用药明显,抑瘤率尼美舒利组为44.33％,顺铂组为53.61％,联合用药组为80.41％ (P ＜0.05).Caspase-3的表达率在联合用药组(67.43±23.57)％、顺铂组(48.40±20.37)％、尼美舒利组(38.65±15.37)％明显高于对照组(27.63±13.03)％,P＜0.05,联合用药组Caspase-3表达率(67.43±23.57)％高于顺铂组(48.40±20.37)％和尼美舒利组(38.65±15.37)％,P＜0.05.Ki67的表达率在联合用药组(24.34±15.90)％、顺铂组(40.85±22.47)％、尼美舒利组(53.33±19.67)％低于对照组(80.43±16.88)％,P＜0.05,且联合用药组Ki67的表达率(24.34±15.90)％低于顺铂组(40.85±22.47)％和尼美舒利组(53.33±19.67)％,P＜0.05.结论 尼美舒利可抑制人肺癌裸鼠移植瘤的生长,与顺铂联合可增强顺铂对肺腺癌A549细胞裸鼠移植瘤的抑制作用,其机制可能与抑制肿瘤细胞Ki67表达,增强Caspase-3表达,抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡有关.     

尼美舒利颗粒治疗儿童发热的疗效观察

目的:观察尼美舒利颗粒治疗儿童发热的临床疗效及安全性.方法:随机将伴有高热症状的急性上呼吸道感染(上感)患儿210例分为两组,治疗组110例给予口服尼美舒利治疗,对照组100例给予对乙酰氨基酚治疗,观察记录用药40 mln～8 h体温变化,评价退热效果.结果:治疗组起效快于对照组,40 min时体温明显降低(t=5.2,P<0.01),差异有统计学意义;2 h、3 h时两组体温比较差异无统计学意义(P>0.05);1 h、4 h、6 h、8 h时治疗组体温明显低于对照组,t分别为6.48、12.38、13.94、15.68,P均<0.01,差异有统计学意义.结论:尼美舒利对儿童退热起效快,作用强,维持时间长.     

HPLC测定血浆中尼美舒利浓度

目的建立测定血浆中尼美舒利（Nim）的反相高效液相色谱法。方法血浆样品用乙腈沉淀蛋白,高速离心后取20出上清进样。以HigginsTMC18柱,流动相为有机相（甲醇：乙腈=400：275）：水相（乙酸：水=1：60）=70：30,缬沙坦为内标,在波长290Nm处检测,流速1．0mL／min,柱温：30℃。结果在0．11-11．0μg／mL浓度范围内,峰面积比与浓度呈良好线性关系,r=0．9996。最低检测限为0．11μg/mL。结论用本方法测定20例单剂量po100mgNim的血药浓度。结果满意。     

Nimesulide Alters Cell Recruitment into Mitosis in Murine Intestinal Crypts Without Influencing the Cell Production Rate

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) that exhibit COX-2 selectivity is associated with fewer gastrointestinal side effects than seen with more traditional NSAIDs. To determine whether the early effects on cell kinetics in the intestinal mucosal epithelium described after COX-2 selective inhibition are sustained following continuous therapy with these inhibitors, assessments of morphometry and cryptal cell proliferation in the murine small intestinal mucosa were made at 24 hr after treatment with indomethacin, a dual COX inhibitor (10 mg/kg body weight intraperitoneally), nimesulide, a selective COX-2 inhibitor (15 mg/kg body weight intraperitoneally), or vehicle. Nimesulide-treated intestine was elongated beyond control values, in contrast to the shorter indomethacin-treated intestine, but anomalous villous forms were present in both treated groups. Both treatments induced expansion and contraction of proliferating compartments in the crypts in different regions of the intestine but nimesulide did not alter crypt cell production rates, in contrast to the down-regulation induced by indomethacin. These findings may provide some of the fundamental basis for the gut-sparing properties seen in patients treated with COX-2 selective inhibitors.     

Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice

Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.     

Mucoadhesive tablets for buccal administration containing sodium nimesulide

The possibility of improving the flux of nimesulide across the buccal mucosa using the drug in the form of a sodium salt was investigated in our study. The salt form may increase to flux across buccal membrane, starting from a suspension; its lower permeation coefficient is compensated by a higher concentration gradient. The salt was inserted into a mucoadhesive tablet for buccal administration. The tablets were designed to prevent the loss of the drug into the saliva by means of a protective layer and placed on the area not in contact with the mucosa. Ten volunteers were used. The in vitro release from mucoadhesive tablets was examined through a porcine buccal mucosa, using a standard Franz cell, modified for present purposes. The advantages of a higher concentration gradient for the flux, related to a higher solubility of the salt, and to a sufficiently high permeation coefficient of the drug, despite the ionized form, could not be completely exploited, because the composition of the formulation destroys the chemical form of the drug.     

尼美舒利对胃癌细胞BGC823 COX-2、VEGF表达的影响

目的 研究尼美舒利（Nimesulide）对人胃癌细胞株BGC-823增殖和凋亡的干预作用，揭示其抗癌机制。方法 采用MTT法、流式细胞仪等检测细胞增殖、细胞周期和凋亡率以及细胞的形态学改变，同时检测尼美舒利对胃癌细胞COX-2、VEGF表达的影响。结果 尼美舒利抑制胃癌细胞的IC50μM／L。增殖抑制率达到80．31％，流式细胞仪分析发现100-200μM／L的尼美舒利作用48h后，细胞被阻滞于S期，凋亡率分别为5．69％，10．58％；光学显微镜观察到凋亡典型的形态学特征；免疫细胞化学结果显示尼美舒利作用后能降低COX2、VEGF蛋白表达，与对照组比较，具有非常显著性差异（P〈0．01）。结论 尼美舒利能显著抑制人胃癌细胞株BGC-823的生长，此作用可能与降低COX2、VEGF蛋白表达有关。     

尼美舒利对慢性牙周炎治疗效果的评价

目的:评价尼美舒利对慢性牙周炎的治疗效果。方法:选择136名慢性牙周炎患者，所有患者均进行牙周基础治疗，然后分别应用尼美舒利和甲硝唑治疗4周。在牙周治疗前及治疗2和4周后常规临床检查，记录探诊出血、菌斑指数和探诊深度，分别比较两种药物对慢性牙周炎的临床治疗效果。 结果:在临床治疗中观察到尼美舒利和甲硝唑均能有效减轻牙周炎症程度，但尼美舒利能显著降低探诊深度（P<0.05）;尼美舒利治疗慢性牙周炎的显效率明显高于甲硝唑治疗组（P<0.05）。 结论:与甲硝唑相比较，尼美舒利对慢性牙周炎的临床治疗效果更显著。     

尼美舒利对正常小鼠免疫功能的影响

目的：研究尼美舒利对免疫功能的影响。方法：采用碳粒廓清法、二硝基氟苯诱导迟发型变态反应试验法、抗体形成测定法及免疫器官重量法，评价尼美舒利对正常小鼠免疫功能的作用。结果：尼美舒利能增强二硝基氟苯诱导的迟发型变态反应，并且提高抗体水平增加脾脏重量。结论：尼美舒利能增强细胞免疫和体液的免疫功能。     

RP-HPLC法测定自制尼美舒利分散片含量及有关物质

目的:建立RP-HPLC法测定尼美舒利分散片的含量及有关物质。方法:采用DiamonsilTM C18(250 mm×4.6mm,5μm)色谱柱,乙腈-0.01 mol/L磷酸二氢钾(三乙胺调pH=6.5)(55∶45)为流动相。检测波长254 nm,流速1.0 ml/min。结果:尼美舒利与各杂质及降解产物分离良好,在150～350μg/ml范围内线性关系良好(r=0.9999),平均回收率99.75%,RSD为0.82%,最低检测限为35 ng,最低定量限为110 ng。结论:该方法简便、快速、准确、灵敏度高、重复性好,可用于尼美舒利含量及有关物质的测定。