塞莱昔布超前镇痛在骨科手术的应用

目的研究塞莱昔布超前镇痛与骨科手术术后疼痛、镇痛药物的使用、不良反应以及与外周血前列腺素E2(PGE2)的关系。方法将80例骨科下肢手术病人随机均分为塞莱昔布组(观察组)和安慰药组(对照组),分别于术前1h及此后12、24h给予塞莱昔布或安慰药。采用联合腰麻,术后行病人静脉自控镇痛(PCIA),并行镇痛评估,记录术后镇痛药的总用量,观察不良反应。手术结束时及术后24h各取外周血2ml,检测PGE2浓度。结果两组间手术结束时、术后1、12、24、48hVAS差异无显著意义。但观察组术后2、4、8hVAS显著低于对照组(P<0.01)。观察组术后48h静脉曲马多用量显著低于对照组(P<0.05),且不良反应亦低于对照组(P<0.05)。观察组术后24h血清中PGE2浓度显著低于对照组(P<0.01)。结论塞莱昔布超前镇痛用于骨科手术,能有效缓解术后疼痛,减轻炎症反应,减少术后镇痛药的使用和不良反应。     

Differential inhibition of cyclooxygenase-1 (COX-1) and-2 (COX-2) by NSAIDS: Consequences on anti-inflammatory activity versus gastric and renal safety

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory) effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance of COX-2 in normal tissue.     

Efficacy of lumiracoxib in relieving pain associated with knee osteoarthritis: a 6‐week,randomized, double‐blind,parallel‐group study

Aim: The aim of the current study was to assess the efficacy, safety, and tolerability of lumiracoxib 200 mg once daily (o.d.) in relieving osteoarthritis (OA) knee pain in patients in China, Taiwan, and South Korea. Methods: Patients of either sex (aged ≥ 18 years) with symptomatic, primary OA of the knee for ≥ 3 months were eligible for inclusion if they had OA pain intensity of ≥ 40 mm (100 mm visual analogue scale [VAS]) in the target knee joint during the previous 24 h. Patients were required to undergo regular non‐steroidal anti‐inflammatory drug therapy for ≥ 6 weeks. After 3–7 days of screening, patients were randomized (1 : 1) to receive either lumiracoxib 200 mg o.d. or celecoxib 200 mg o.d. The primary efficacy comparison between the study groups was overall OA pain intensity (VAS) in the target knee after 6 weeks of treatment. Results: The mean overall OA pain intensity (VAS) in the target knee after 6 weeks decreased from 60.6 mm to 35.7 mm and 60.5 mm to 36.1 mm in the lumiracoxib and celecoxib groups, respectively. Both study groups showed similar results in terms of improvement in both patient's and physician's global assessment of disease activity and functional health status. The percentage of adverse events (AEs) in the lumiracoxib and celecoxib groups (40.3% and 37.9%, respectively) was similar, as was the proportion of treatment‐related AEs (21.0% and 18.2%, respectively). Conclusions: Lumiracoxib 200 mg o.d. provided effective and well‐tolerated pain relief similar to that achieved with celecoxib 200 mg o.d. in knee OA patients.     

2005～2007年我国非甾体抗炎药市场应用分析

目的：以骨骼肌肉系统使用非甾体抗炎药物为例，分析该类药物在2005～2007年的销售数量、销售金额及生产厂家风云榜。方法：采用药物分类累加的方法统计2005～2007年非甾体抗炎药的销售数量和金额排序，并对前10位药品销售数量和金额对比，及前10位厂家对比。结果：双氯芬酸稳居销售榜首，美洛昔康、布洛芬等药物位居其后。结论：新一代的非甾体抗炎药已经占据主要市场，各类药物各有特色，但是仍需注意其消化系统及心血管系统的不良反应。     

Do NSAIDs affect the progression of osteoarthritis?

NSAIDs are widely used to alleviate the symptoms of OA. It remains controversial as to what effects these agents have on the progression of OA. In vitro studies showed several types of NSAIDs (e.g., sodium salicylate, indomethacin) inhibited the synthesis of cartilage matrix component, but some types of NSAIDs (e.g., aceclofenac, meloxicam, nimesulide) increased the matrix component synthesis and protected the chondrocytes against apoptosis, while others (e.g., piroxicam) had no effects. Studies in animal models verified that NSAIDs had favourable or detrimental action on OA progression, even the same NSAID (e.g., naproxen, tiaprofenic acid) had reverse effects on articular cartilage in different studies. Preliminary clinical trials revealed some NSAIDs such as indomethacin had a negative influence on joint structure, other NSAIDs such as diclofenac and naproxen had no acceleration of radiographic damage to OA within 2-years of treatment. So far, there are no convincing data to show the widely used NSAIDs and recommended selective COX-2 inhibitor have favourable effects on cartilage. Therefore, it is necessary and valuable to clarify the effects of these NSAIDs on cartilage in patients with OA using validated non-invasive methods such as MRI.     

Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease

Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.     

Groups I,II and III extracellular phospholipases A2: Selective inhibition of group II enzymes by indomethacin but not other NSAIDs

The three types (groups I, II and III) of stable extracellular 14 kDa phospholipase A₂ enzymes differ in their primary amino acid sequences and their properties. It may thus be possible to design low-molecular weight inhibitors targeted to the secretory form of mammalian PLA₂. this enzyme has been implicated in inflammatory disorders. We have studied the inhibition of four distinct PLA₂ enzymes by a range of NSAIDs, using³H-oleate release from prelabelled membranes ofE. coli for assay. The enzymes used were cobra venom PLA₂ (Naja naja, a group I enzyme), bee venom PLA₂ (Apis mellifera, group III), recombinant human synovial PLA₂ (group II) and rat peritoneal PLA₂ (group II). Under the conditions of the³H-oleateE. coli assay, 1 mM concentrations of aspirin, sodium salicylate, paracetamol (acetaminophen), oxphenbutazone, ibuprofen, flurbiprofen and nabumetone failed to inhibit significantly any of the four enzymes. However, indomethacin inhibited all four enzymes, although effects were greatest on the two group II enzymes (rat peritoneal and human synovial PLA₂). Approximate IC₅₀ values were 28 and 35 M, respectively. Inhibition by indomethacin was not time dependent and was greater at micromolar rather than millimolar levels of calcium. We conclude that indomethacin but not the other tested classes of NSAID inhibits the group II PLA₂ enzyme in a selective manner and suggest that this may be relevant both to its clinical spectrum and to the design of novel pharmaceutical leads.