兰索拉唑针剂治疗十二指肠球部溃疡出血的多中心临床研究

目的 探讨兰索拉唑针剂治疗十二指肠球部溃疡出血的临床效果及安全性.方法 采用多中心、随机、阳性药物、平行对照研究.将2005年4月-11月收集的216例经胃镜证实的十二指肠球部溃疡出血患者随机分为两组,试验组110例给予兰索拉唑(商品名:奥维加)30 mg、对照组106例给予奥美拉唑钠(商品名:洛赛克)40 mg静脉滴注,每12 h 1次,连续5 d,结果共有212例患者可供疗效评价及安全性评价.试验组的临床显效率为73.39%,总有效率为95.41%,对照组的临床显效率为81.55%,总有效率为95.15%,两组间差异无统计学意义(P＞0.05).止血时间试验组为(31.90±18.58)h,对照组为(28.00±18.31)h;止血率试验组为98.17%,对照组为99.03%,两组问差异均无统计学意义(P＞0.05).两组不良反应主要为白细胞减少、转氨酶轻度升高和皮疹(P＞0.05).结论 兰索拉唑针剂是治疗十二指肠球部溃疡出血有效且安全的药物.     

兰索拉唑联合铝碳酸镁治疗消化性溃疡的长期疗效分析

目的：探讨溃疡愈合质量对消化性溃疡复发的影响。方法：将68例十二指肠球部溃疡合并幽门螺杆菌(H．Pylori)感染患者随机分为：试验组38例,对照组30例。2组均先给予标准3联疗法根除H．Pylori,1周后试验组,兰索拉唑30mg每日2次,联合铝碳酸镁(商品名,达喜)1000mg每日3次;对照组,兰索拉唑30mg每日2次;继续治疗4周。停药4周后观察内镜下溃疡愈合率、胃粘膜组织学改变;随访1年内溃疡复发情况。结果：停药4周后内镜下溃疡愈合率分别为,试验组94．7%,对照组80．0%,两者比较无显著性差异(P＞0．05)。组织学观察显示粘膜层厚度、腺体密度和腺管形态恢复,试验组显著优于对照组(P＜0．05);1年内溃疡复发率,试验组2．8%,对照组25．0%,两者比较有显著性差异(P＜0．05)。结论：兰索拉唑联用铝碳酸镁能提高溃疡愈合质量,减少溃疡复发,显著优于单用兰索拉唑。     

Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study

Purpose

To evaluate the efficacy and upper gastrointestinal (UGI) safety of celecoxib, compared with nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), among patients with osteoarthritis.

Methods

A total of 13 274 osteoarthritis patients from 39 countries were randomly assigned to double-blind treatment with either celecoxib 100 mg twice daily (BID), celecoxib 200 mg BID, or nonselective NSAID therapy (diclofenac 50 mg BID or naproxen 500 mg BID) for 12 weeks. Standard validated measures were used to assess osteoarthritis efficacy. Serious UGI events were evaluated by 2 blinded, independent, gastrointestinal events committees.

Results

Results from all primary efficacy assessments showed that both dosages of celecoxib were as effective as NSAIDs in treating osteoarthritis. Significantly more ulcer complications occurred within the nonselective NSAID group (0.8/100 patient-years) compared with the celecoxib group (0.1/100 patient-years) (odds ratio = 7.02; 95% confidence interval [CI], 1.46 to 33.80; P =.008). There were fewer ulcer complications in the celecoxib group compared with the NSAID group, both in patients taking concomitant aspirin and those not taking aspirin, but the difference reached statistical significance only in the latter comparison. The number of cardiovascular thromboembolic events was low and not statistically different between the groups (eg, myocardial infarction rates: celecoxib 10 events [0.55/100 patient-years] vs NSAIDs 1 event [0.11/100 patient-years], (P =.11), but the study was not powered to detect such differences.

Conclusions

In the treatment of osteoarthritis, celecoxib is as effective as the nonspecific NSAIDs naproxen and diclofenac, but has significantly fewer serious upper gastrointestinal events.     

Comparative study of the clinical efficacy of the selective cyclooxygenase-2 inhibitor celecoxib compared with loxoprofen in patients with frozen shoulder

Abstract

Background This is a randomized comparative study of the efficacy of celecoxib and loxoprofen in patients with frozen shoulder (scapulohumeral periarthritis).

Methods Patients with frozen shoulder who presented with pain as the symptom were divided at random into a celecoxib treatment group (100 mg/dose, twice daily; n = 37) and a loxoprofen treatment group (60 mg/dose, 3 times daily; n = 33). Medication was continued for 1–2 weeks in each group.

Results Each patient was asked to rate the pain on a visual analog scale (score 0–5). This score significantly improved (indicating marked alleviation of pain) in both the celecoxib group (from 3.41 ± 0.86 before treatment to 2.30 ± 1.02 after treatment) and the loxoprofen group (from 3.73 ± 0.67 before treatment to 2.76 ± 0.96 after treatment). In the analysis of disappearance of pain, the percentage of patients showing disappearance of nocturnal pain was significantly higher in the celecoxib group (71.4 %) than in the loxoprofen group (36.8 %).

Conclusions The results confirm that celecoxib is comparable to loxoprofen in terms of analgesic efficacy in patients with frozen shoulder. Among other findings, we report that celecoxib was more effective for nocturnal pain than loxoprofen.     

雷贝拉唑与兰索拉唑对幽门螺杆菌阳性的消化性溃疡患者安全性与有效性的Meta分析

目的 比较雷贝拉唑与兰索拉唑对根除幽门螺杆菌阳性消化性溃疡患者的安全性与有效性.方法 计算机检索PubMed、EMbase、CNKI、万方数据库和维普数据库查找所有比较雷贝拉唑和兰索拉唑根除幽门螺杆菌阳性消化性溃疡的随机对照试验,检索时间为建库到2014年1月24日.按照纳入及排除标准由两名系统性评价员独立进行随机对照试验的筛选,资料提取和质量评价后采用RevMan 5.2软件进行Meta分析.结果 纳入9个研究,共1 421例患者.安全性方面,雷贝拉唑与兰索拉唑不良反应发生率比较,差异无统计学意义[OR=1.10,95％ CI（0.71～1.71）,P＞0.05];药物依从性方面,雷贝拉唑与兰索拉唑比较,差异无统计学意义[R=0.51,95％CI（0.13 ～1.92）,P＞0.05];有效性方面,雷贝拉唑对幽门螺杆菌根除率优于兰索拉唑,差异有统计学意义[OR=0.65,95％ CI（0.47 ～0.88）P ＜0.01],.雷贝拉唑对溃疡愈合率亦优于兰索拉唑,差异有统计学意义[OR =0.36,95％ CI（0.20～0.65）,P＜0.01].结论 雷贝拉唑有效性优于兰索拉唑,且安全性上无差异.因原始研究的质量高低不一,建议临床上谨慎选择使用,需要更多的大样本多中心的随机对照试验进一步论证.     

The effect of selective cyclooxygenase-2 inhibitor on human osteoclast precursors to influence osteoclastogenesis in vitro

The inducible prostaglandin synthesis enzyme, cyclooxygenase-2 (COX-2), is involved in bone resorption and osteoclastogenesis, and acts indirectly through prostaglandin E2 (PG E2) produced by osteoblastic cells. This study was undertaken to investigate whether celecoxib (a selective COX-2 inhibitor) has a direct effect on human osteoclast precursors to influence osteoclastogenesis in vitro. Human peripheral blood mononuclear cells (PBMCs) were cultured on glass coverslips and dentine slices with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage colony stimulating factor (M-CSF). COX inhibitors including celecoxib were added to the cultures. Osteoclast formation was assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), and the functional evidence of lacunar resorption pits on dentine slices was assessed. Celecoxib and indomethacin inhibited osteoclast formation and the extent of lacunar resorption in a dose-dependent manner, but the effect of indomethacin was less than that of celecoxib. Mofezolac affected neither the number of TRAP-positive MNCs nor the extent of lacunar resorption pits. These results indicate that celecoxib influences not only osteoclast formation through osteoblastic cells but also acts directly on circulating osteoclast precursors to influence human osteoclast differentiation. The effect of celecoxib on osteoclast precursors may be related to the COX-2 signal pathway.     

The effect of selective cyclooxygenase-2 inhibitor on human osteoclast precursors to influence osteoclastogenesis in vitro

Abstract

The inducible prostaglandin synthesis enzyme, cyclooxygenase-2 (COX-2), is involved in bone resorption and osteoclastogenesis, and acts indirectly through prostaglandin E2 (PG E2) produced by osteoblastic cells. This study was undertaken to investigate whether celecoxib (a selective COX-2 inhibitor) has a direct effect on human osteoclast precursors to influence osteoclastogenesis in vitro. Human peripheral blood mononuclear cells (PBMCs) were cultured on glass coverslips and dentine slices with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage colony stimulating factor (M-CSF). COX inhibitors including celecoxib were added to the cultures. Osteoclast formation was assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), and the functional evidence of lacunar resorption pits on dentine slices was assessed. Celecoxib and indomethacin inhibited osteoclast formation and the extent of lacunar resorption in a dose-dependent manner, but the effect of indomethacin was less than that of celecoxib. Mofezolac affected neither the number of TRAP-positive MNCs nor the extent of lacunar resorption pits. These results indicate that celecoxib influences not only osteoclast formation through osteoblastic cells but also acts directly on circulating osteoclast precursors to influence human osteoclast differentiation. The effect of celecoxib on osteoclast precursors may be related to the COX-2 signal pathway.     

Neutropenia does not prevent etodolac- or indomethacin-induced gastrointestinal damage in the rat

Neutrophils have been implicated in the acute formation of gastric mucosal erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present study were to determine, in rats, the role of neutrophils in the pathogenesis of etodolac- and indomethacin-induced gastrointestinal ulceration and blood loss. Both drugs caused gastrointestinal ulceration, which was associated with increased blood loss, a rise in plasma haptoglobin concentration, and a rise in the number of circulating neutrophils. A marked infiltration of neutrophils occurred only in ileal tissue. Pretreatment with a selective antineutrophil serum induced a significant neutropenia, which failed to inhibit either etodolac- or indomethacin-induced gastrointestinal ulceration and blood loss. A further study demonstrated that the antineutrophil serum did not prevent gastric erosions induced by indomethacin, but it inhibited carrageenan paw edema, which is dependent, in part, on neutrophil infiltration and activation. It is concluded that neutrophils do not contribute to gastrointestinal ulceration and blood loss induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with previous studies, our results provide no evidence that neutrophils contribute to indomethacin-induced acute gastric erosion formation.     

“硫酸软骨素”和“塞来昔布”治疗成人大骨节病患者的成本效果分析

目的对"硫酸软骨素"和"塞来昔布"治疗成人大骨节病患者进行成本效果分析,为筛选价格低廉、效果好和副作用小的治疗药物提供依据。方法采用流行病学实验研究的方法,选择阿坝州大骨节病流行区中的成人大骨节病患者200例,随机分为2组,分别服用"硫酸软骨素"和"塞来昔布",长期随访记录WOMAC指数评分和服药情况,计算并比较两组的成本效果。结果当以WOMAC指数改变幅度作为效果指标时,硫酸软骨素组和塞来昔布组的成本效果比C/E1分别为87.07元vs 154.67元,以硫酸软骨素组为基准,塞来昔布组的增量成本效果比△C/△E1为200.11元;当以有效率作为效果指标时,两组的C/E2分别为3 085元vs 3 078元,△C/△E2为3 077元。结论总体上可以认为服用硫酸软骨素较服用塞来昔布方案为优。但这也不是绝对的,如果资源充分,也可考虑选择服用塞来昔布。     

Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo

OBJECTIVE: To determine the upper gastrointestinal (GI) tolerability of celecoxib, naproxen, and placebo in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: An analysis of 5, 12-week, randomized, double blind, parallel group, placebo controlled clinical trials was conducted. In these trials, patients were randomized to: naproxen 500 mg bid (n = 1,099), placebo (n = 1,136), celecoxib 50 mg bid (n = 690) (subtherapeutic dose), celecoxib 100 mg (n = 1,131) or 200 mg bid (n = 1,125) (therapeutic dose), or celecoxib 400 mg bid (n = 434) (supratherapeutic dosage). The incidence and time until moderate to severe abdominal pain, dyspepsia, nausea, and any of the aforementioned 3 upper GI symptoms (composite endpoint) were determined using time-to-event analysis. RESULTS: The cumulative incidences of moderate to severe abdominal pain, dyspepsia, or nausea (composite endpoint) were: naproxen 500 mg (12.0%; 95% CI 9.9%-14.0%), celecoxib 50 mg bid (7.1%; 95% CI 5.0%-9.2%), celecoxib 100 mg bid (7.8%; 95% CI 6.0%-9.5%), celecoxib 200 mg bid (8.1%; 95% CI 6.4%-9.9%), celecoxib 400 mg bid (6.0%; 95% CI 3.6%-8.4%), and placebo (8.5%; 95% CI 6.5%-10.8%). After controlling for independent predictors of the composite endpoint, relative risks (RR) for the various treatments relative to naproxen 500 mg bid were: celecoxib 50 mg (RR 0.54; 95% CI 0.37-0.77; p < 0.001), celecoxib 100 mg (RR 0.60; 95% CI 0.45-0.80; p < 0.001), celecoxib 200 mg bid (RR 0.63; 95% CI 0.47-0.83; p = 0.001), celecoxib 400 mg bid (RR 0.56; 95% CI 0.35-0.89; p = 0.015), and placebo (RR 0.63; 95% CI 0.47-0.85; p = 0.002). After controlling for independent predictors of the composite endpoint, celecoxib treatment group patients did not differ from placebo patients when reporting the composite endpoint, with p values ranging from 0.40 to 0.96. CONCLUSION: The upper GI tolerability of celecoxib is superior to naproxen. A dose-response relationship between celecoxib and upper GI symptoms was not apparent.     

Gastrointestinal Damage Induced by Celecoxib and Rofecoxib in Rats

Five experimental models were developed in different groups of Wistar rats (N = 15) to study selective COX-2-inhibitor NSAIDs such as celecoxib and rofecoxib, as follows: (1) dose-dependent oral Celecoxib and Rofecoxib for 5 days, and 24 hr after oral indomethacin; (2) Same as 1 but subcutaneously; (3) gastric ulcer induced by glacial acetic acid; (4) duodenal ulcer induced by cysteamine; and (5) stress by immobilization and immersion in water at 15°C for 6 hr. Celecoxib and Rofecoxib, either orally or subcutaneously, did not produce necrotic lesions in healthy gastrointestinal mucosa (0%), showing normal histology. In contrast, previously indomethacin-induced lesions were aggravated (90%, P < 0.001). Total necrosis in the small intestine as well as increased ulcers and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also aggravation of the necrotic gastric area in stress (60–90%, P < 0.05). Celecoxib and rofecoxib showed neutrophilia (5000/mm³) similar to that with indomethacin. In contrast, there was no leukocyte infiltration in the gastric mucosa; thus, we can consider it a selective COX-2 NSAID. In conclusion, celecoxib and rofecoxib at doses causing COX-2 but not COX-1 inhibition did not produce toxic lesions in healthy gastrointestinal mucosa, yielding a broad therapeutic margin. In contrast, when administered in altered gastrointestinal mucosa, they aggravated and complicated gastric ulcers as well as necrosis in the small intestine, consequently restricting their clinical use.     

NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis

Background

Studies have demonstrated the success of augmentation of antidepressant therapy with nonsteroidal anti-inflammatory drugs (NSAID) in decreasing depressive symptoms; however, little is known about the benefit of NSAID therapy on depressive symptoms.

Methods

This study pooled data from 5 postapproval trials, each trial a 6-week, multicenter, randomized, double-blinded, placebo-controlled, active-comparator, parallel-group study in subjects with active osteoarthritis. Subjects were randomized to placebo group, ibuprofen 800 mg 3 times daily or naproxen 500 mg twice daily group, or Celebrex 200 mg daily group. Apart from different ethnicities enrolled, these trials had identical study designs. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Outcomes measured were change in PHQ-9 score after 6 weeks of NSAID therapy and change in classification of depression with a PHQ-9 score ≥10 as a marker of depression.

Results

There were 1497 patients included. Median PHQ-9 score was similar in all 3 groups at baseline and after 6 weeks of treatment. Multivariable regression analysis demonstrated a detectable effect in lowering PHQ-9 score in the ibuprofen or naproxen group (−0.31) and Celebrex group (−0.61) (P = .0390). With respect to the change in classification of depression, logistic regression analysis demonstrated a trend towards significant treatment effect of all NSAIDs compared with placebo.

Conclusion

Our analysis of pooled data from 5 postapproval trials shows that NSAID usage demonstrates a trend towards reduction of depression symptoms in patients with osteoarthritis based upon PHQ-9 scores. Future clinical trials should investigate this association with maximum dosage of drugs, increased treatment duration, and monitoring of social and environmental changes.     

奥美拉唑、泮托拉唑、兰索拉唑和埃索美拉唑对反流性食管炎患者症状缓解的比较研究

目的比较奥美拉唑、泮托拉唑、兰索拉唑和埃索美拉唑对反流性食管炎患者症状缓解之间的差异。方法320例内镜诊断为反流性食管炎患者被随机分为4组,并分别服用奥美拉唑20mg,1次／d,8周;兰索拉唑30mg,1次／d,8周;泮托拉唑40mg,1次／d,8周;埃索美拉唑40mg,1次／d,8周。用six—point scale（0：无,1：轻度,2：轻度-中度,3：中度,4：中度-重度,5：重度）评价服用4种质子泵抑制剂后7天内的烧心和反流症状。结果埃索美拉唑组的平均烧心积分比其他质子泵抑制剂下降更迅速。埃索美拉唑组第1～5天的烧心症状完全消失率明显高于奥美拉唑组（P值分别为0．0054、0．0072、0．0089、0．0107、0．0134）、兰索拉唑组（P值分别为0．0043、0．0034、0．0044、0．0011、0．0052）、泮托拉唑组（P值分别为0．0156、0．0003、0．0005、0,0024、0．0172）。内镜下反流性食管炎愈合率4组之间无明显差异。结论埃索美拉唑比奥美拉唑、兰索拉唑、泮托拉唑更迅速地减轻反流性食管炎患者的烧心和反流症状。     

Celecoxib prevents juxta-articular osteopenia and growth plate destruction adjacent to inflamed joints in rats with collagen-induced arthritis

The effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on juxta-articular osteopenia and growth plate destruction adjacent to inflamed joints was investigated in rats with collagen-induced arthritis. Forty rats were assigned to the following six groups: (1) an untreated arthritis group; (2–5) arthritis rats receiving indomethacin (3 mg/kg per day), dexamethasone (0.2 mg/kg per day), or celecoxib (5 or 50 mg/kg per day), and (6) normal control rats. Drugs were administered for 2 weeks from the onset of arthritis. Then the hind paws were measured. Juxta-articular osteopenia and growth plate destruction adjacent to inflamed joints were also assessed using plain radiography, bone mineral density measurement, histology, and histomorphometry. Each treatment reduced inflammation, but only dexamethasone and high-dose celecoxib prevented bone loss adjacent to inflamed joints and significantly decreased bone resorption. In contrast, no treatment affected bone formation parameters. Growth plate destruction adjacent to inflamed joints was prevented by indomethacin, dexamethasone, and high-dose celecoxib. Although dexamethasone abolished inflammation, growth plate destruction was still observed. In conclusion, among the various drugs tested, only celecoxib had a preventive effect on both growth plate destruction and bone loss adjacent to inflamed joints in this arthritis model.     

Improved symptom relief and duodenal ulcer healing with lansoprazole, a new proton pump inhibitor, compared with ranitidine.

The purpose of this study was to compare duodenal ulcer healing, symptom relief, and safety of lansoprazole (a new proton pump inhibitor) given at doses of 30 mg and 60 mg, in the morning with ranitidine 300 mg at bedtime. Two hundred and eighty nine patients were enrolled over a 20 month period in a double blind randomised parallel group comparative study set in outpatient endoscopy units of six United Kingdom medical centres. Patients were randomised to receive lansoprazole 30 mg in the morning (n = 95), 60 mg in the morning (n = 96), or ranitidine 300 mg at bedtime (n = 98) for four weeks. Efficacy was assessed by gastroscopy at study entry and after two and four weeks of treatment. Symptom relief was monitored by patient diaries and physician review at two and four weeks. Both doses of lansoprazole resulted in significantly greater ulcer healing than ranitidine after two and four weeks. Respective healing rates on lansoprazole 30 mg, 60 mg, and ranitidine 300 mg were 78%, 80%, and 60% after two weeks and 93%, 97%, and 81% after four weeks. Patients on lansoprazole 30 mg (p = 0.002) and lansoprazole 60 mg (p = 0.026) also recorded greater relief of night time pain in the diary cards during the first seven days of treatment than those on ranitidine. Patients on lansoprazole 60 mg reported significantly better pain relief at their two week visit compared with those receiving ranitidine (p = 0.007). There were no differences between treatment groups in the occurrence or pattern of adverse drug reactions during the trial. It is concluded that for patients with duodenal ulcer, lansoprazole 30 mg or 60 mg is associated with faster ulcer healing and better symptom relief than ranitidine 300 mg at bedtime. There were no significant differences between lansoprazole 30 mg and 60 mg. These data indicate that lansoprazole should be used at a once daily dose of 30 mg for the treatment of duodenal ulcer.     

塞来昔布联合热疗对胰腺癌细胞周期的影响

背景：选择性环氧合酶-2抑制剂塞来昔布和热疗对肿瘤细胞生长均有抑制作用。目的：研究塞来昔布联合热疗对人胰腺癌细胞周期的影响。方法：流式细胞仪检测常规热疗、塞来昔布以及两者联合对人胰腺癌细胞株SW1990周期的影响。40只新生裸鼠建立胰腺癌SW1990细胞移植瘤模型，并分为对照组、高强聚焦超声（HIFU）热疗组、塞来昔布组和联合组，逆转录聚合酶链反应（RT—PCR）检测p21^Wafl、p27^Kipl、p16、p53在各组细胞和移植瘤中的表达。免疫组化方法检测移植瘤组织中p53表达。结果：流式细胞仪结果显示常规热疗组、塞来昔布组和联合组SW1990细胞周期阻滞，尤以联合组抑制作用最明显（G1期77．8％，S期6．5％）。体外实验RT-PCR示p21^Wafl和p53在4组中的表达无明显差异；p27^Kipl。在常规热疗组、塞来昔布组和联合组中表达上调，尤以联合组更明显；p16在常规热疗组和联合组中表达明显上调。体内实验RT—PCR示p21^Wafl、p27^Kipl。和p53在对照组和塞来昔布组中表达相对较强；p16在HIFU热疗组、塞来昔布组和联合组中的表达极弱。免疫组化染色示对照组和塞来昔布组中有p53蛋白表达。结论：常规热疗、塞来昔布以及两者联合均有抑制胰腺癌细胞周期的作用，其机制可能为上调p27^Kipl、p16表达而诱导细胞周期G1期阻滞以及抑制S期发展。HIFU热疗可能通过促焦点处肿瘤细胞迅速坏死，诱导周边肿瘤组织细胞周期阻滞。从而抑制肿瘤细胞生长。     

Celecoxib modulates hypertrophic signalling and prevents load-induced cardiac dysfunction

In human hearts, the transition from cardiac hypertrophy to advanced heart failure (HF) is accompanied by a tremendous increase in Akt phosphorylation. In non-myocardial tissue, the cyclooxygenase (COX)-2 inhibitor celecoxib has been shown to COX-independently inhibit Akt signalling. We studied the effects of celecoxib on Akt signalling and hypertrophic response in myocardium. In rabbit isolated cardiac myocytes celecoxib concentration-dependently (10-100 micromol/L) inhibited the insulin-induced increase in phosphorylation of Akt and its downstream targets, GSK-3beta and p70 S6 kinase, by reducing the phosphorylation level of the upstream regulator PTEN. Inhibition of Akt signalling was accompanied by a significant suppression of characteristic features of cardiac hypertrophy: Celecoxib concentration-dependently suppressed the agonist-induced enhancement of total protein synthesis and BNP mRNA expression. In mice (C57BL/6NCrl) subjected to left ventricular (LV) pressure overload by aortic banding, celecoxib treatment (50mg x kg-1 x d-1) significantly attenuated LV dilation and contractile dysfunction compared with placebo-treated mice. Moreover, celecoxib significantly reduced mortality 8 weeks after banding. Thus, celecoxib can be used to titrate Akt signalling and hypertrophic response in myocardium. It reduces load-induced LV dilation, contractile dysfunction and mortality in vivo. This may have clinical implications for the prevention and treatment of maladaptive hypertrophy and its progression to HF in humans.     

An extensive metabolizer with recurrent ulcer responding to high dose of lansoprazole

A 51-year-old man underwent surgery for duodenal ulcer in 1983. Ulcer recurred several times. Recently, the patient was receiving 30 mg/day of lansoprazole. On June 15, 2001 hemorrhagic recurrent ulcer was diagnosed. Analysis of CYP2C19 enzyme genotype indicated that the patient was a heterozygous extensive metabolizer, suggesting that 30 mg/day of lansoprazole did not produce effective concentrations of drug in the serum. The dose of lansoprazole was increased to 60 mg/day, and intragastric pH monitoring revealed that a pH > or = 3 was maintained for 99.8% of a 24-hour period, as compared with a previous value of 88.3%. After 3 weeks of treatment, endoscopic examination showed that a red scar had formed at the ulcer site.     

钛夹预防消化内镜术后并发症的Meta分析

目的评价使用钛夹关闭内镜下黏膜切除术(endoscopic mucosal resection,EMR)、内镜下黏膜剥离术(endoscopic submucosal dissection,ESD)等术后创面减少术后迟发性出血以及促进创面愈合的有效性。 方法计算机检索2017年10月之前PubMed、EMBASE、Cochrance library三个数据库中公开发表的有关钛夹关闭EMR、ESD术后创面的文献,依据纳入和排除标准将最终入选的文献应用Review Manager 5.3软件分析数据。 结果最终6篇随机对照试验文献纳入研究。Meta分析结果显示：钛夹关闭创面不能减少术后迟发性出血的发生率(OR＝0.43,95% CI：0.14～1.29,P＝0.13),差异无统计学意义;然而创面关闭可以促进创面愈合(OR＝－1.18,95% CI：－1.77～－0.60,P<0.01),差异有统计学意义。 结论钛夹关闭创面不能减少EMR、ESD等术后迟发性出血的发生,但可能促进医源性创面的愈合。