Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.     

\dot{V}_{{{\text{O}}_{2} { \max }}} is not altered by self-pacing during incremental exercise

We tested the hypothesis that incremental cycling to exhaustion that is paced using clamps of the rating of perceived exertion (RPE) elicits higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ values compared to a conventional ramp incremental protocol when test duration is matched. Seven males completed three incremental tests to exhaustion to measure $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ . The incremental protocols were of similar duration and included: a ramp test at 30 W min^?1 with constant cadence (RAMP1); a ramp test at 30 W min^?1 with cadence free to fluctuate according to subject preference (RAMP2); and a self-paced incremental test in which the power output was selected by the subject according to prescribed increments in RPE (SPT). The subjects also completed a $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ ‘verification’ test at a fixed high-intensity power output and a 3-min all-out test. No difference was found for $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ between the incremental protocols (RAMP1 = 4.33 ± 0.60 L min^?1; RAMP2 = 4.31 ± 0.62 L min^?1; SPT = 4.36 ± 0.59 L min^?1; P > 0.05) nor between the incremental protocols and the peak $ \dot{V}_{{{\text{O}}_{2} }} $ measured during the 3-min all-out test (4.33 ± 0.68 L min^?1) or the $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured in the verification test (4.32 ± 0.69 L min^?1). The integrated electromyogram, blood lactate concentration, heart rate and minute ventilation at exhaustion were not different (P > 0.05) between the incremental protocols. In conclusion, when test duration is matched, SPT does not elicit a higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ compared to conventional incremental protocols. The striking similarity of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured across an array of exercise protocols indicates that there are physiological limits to the attainment of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ that cannot be exceeded by self-pacing.     

Clozapine cases with fatal,toxic or therapeutic concentrations

Summary The neuroleptic drug clozapine is used in the treatment of schizophrenia and is characterized by not having the extrapyrimidal side-effects usually shown by neuroleptics. Unfortunately clozapine has other side-effects, which limit its use. This study presents methods for the analysis of clozapine and desmethylclozapine in whole blood and tissue. Case histories and pathology findings are described for 3 autopsy cases with fatal concentrations of clozapine, 5 with toxic concentrations and 2 with therapeutic concentrations together with the concentrations found in a living person.     

川藏高原武警战士遂行任务后两周疲劳情况分析

目的调查川藏高原地区武警战士遂行任务后两周生理心理疲劳状况,比较不同海拔高度、年内执行任务次数对疲劳状态的影响,为制订有效干预措施、迅速恢复执行任务武警战士精神状态提供参考。方法采用整群抽样方式对川藏高原地区某部武警战士160人遂行任务后两周后疲劳状态进行中文版多维疲劳量表(MFI-20)问卷调查。采用SPSS 17.0统计软件进行数据分析。结果虽然同为高原,四川某部海拔明显低于西藏某部,因此战士疲劳状态也有所不同,其总得分48.87±6.39明显低于西藏地区的51.72±7.86;4个维度中,除了活动减少差别无统计学意义外,其余3个维度得分均比西藏地区战士低(P0.05)。海拔越高,疲劳状态越明显;年内执行任务次数越多,各维度和总分越高,高海拔比低海拔差异更为显著,提示高海拔加上任务次数增加会加剧疲劳感。结论高原武警战士遂行任务两周后生理心理疲劳问题值得关注;海拔越高,年内执行任务次数越多,疲劳状态越显著,需采取针对性干预措施。     

消瘀泄浊饮对CKD2~4期患者免疫调节功能及微炎症状态的影响

[目的]评估消瘀泄浊饮对慢性肾脏病(chronic kidney disease,CKD)2~4期患者免疫调节功能及微炎症状态的作用。[方法]选取80例CKD2~4期患者,随机分为两组:对照组40例,仅予基础治疗;治疗组40例,除基础治疗外加用中药汤剂消瘀泄浊饮治疗,1剂/d,分早晚两次服用。治疗12周后,比较两组治疗前后维甲酸相关孤儿受体γt(retinoid-related orphan receptorγt,RORγt)、叉头框转录因子p3(forkhead box p3,Foxp3)mRNA相对表达量,超敏C反应蛋白(high sensitivity-C reactive protein,hs-CRP)及肾功能相关指标水平变化情况。[结果]与治疗前比较,治疗组治疗后RORγt mRNA相对表达量下降(P<0.05),且低于对照组治疗后(P<0.05);Foxp3 mRNA相对表达量升高(P<0.05),且高于对照组治疗后(P<0.05)。与治疗前比较,治疗组治疗后hs-CRP水平下降(P<0.05),且低于对照组治疗后(P<0.05);血肌酐(serum creatinine,sCr)、血尿素氮(blood urea nitrogen,BUN)、24h尿蛋白定量(24-hour urinary protein quantity,24Upr)水平较前下降(P<0.05),其中sCr、BUN水平低于对照组治疗后(P<0.05)。[结论]消瘀泄浊饮能够调节免疫平衡,改善微炎症状态,延缓肾功能恶化,其机制可能与下调RORγt mRNA、上调Foxp3 mRNA水平、调节Th17/Treg平衡相关。     

Long-term follow-up after ESS and balloon sinuplasty: Comparison of symptom reduction and patient satisfaction

Conclusion This is the first controlled study of balloon sinuplasty’s long-term efficacy with the follow-up time over 5 years. The results are in accordance with a previous 2-year-follow-up study. Both techniques retained the efficacy and patient satisfaction on average 6 years after the surgery.

Background Endoscopic sinus surgery (ESS) and balloon sinuplasty are considered as a treatment for chronic rhinosinusitis (CRS) after a failure of conservative therapy. High cost and lack of long-term follow-up studies restrain the use of balloon sinuplasty.

Objective The aim of this study was to compare long-term efficacy and satisfaction in CRS patients who had undergone maxillary sinus operation with either balloon sinuplasty or ESS technique. Previous or additional sinonasal operations were exclusion criteria.

Materials and methods Study patients were recruited from 208 CRS-patients who underwent either ESS or balloon sinuplasty. Patients with nasal polyposis (gradus ≥?2), previous sinonasal surgery, unilateral disease, or immune deficiency were excluded. Altogether 45 patients in the ESS group and 40 patients in the balloon group were included. Of these, 30 and 28, respectively, answered to a phone interview held on average 6 years after primary surgery. Symptom reduction and long-term satisfaction were evaluated by using symptom scores of 19 parameters altogether.

Results Both groups experienced improvement in symptoms and were equally satisfied with the operation. The number of patient-reported acute exacerbations was higher among the balloon dilated patients. Also, the reduction of thick nasal discharge was less evident in the balloon sinuplasty group. Four patients in the balloon sinuplasty group underwent revision surgery. There were no revisions in the ESS group.     

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艾司奥美拉唑在肝胆外科围术期的合理应用分析

目的 了解东方肝胆外科医院（简称"我院"）注射用艾司奥美拉唑钠在肝胆外科围术期应用的合理性,为肝胆手术围术期合理用药提供参考。方法 用回顾性研究方法,通过查阅电子病历、医嘱和检验结果等途径,随机采集了2017年1月至9月300例使用注射用艾司奥美拉唑钠患者的相关信息。300例病例艾司奥美拉唑的使用频次为416次,从给药时间、用药疗程、用法用量、溶剂和应激性溃疡危险因素等方面进行分析。结果 给药时间的合理率是15.67%（47/300）,用药疗程的合理率是10.67%（32/300）,用法的合理率是75%（312/416）,用量的合理率是100%（416/416）,溶媒的合理率为100%（416/416）,具有应激性溃疡危险因素的患者占3.33%（10/300）。结论 我院肝胆外科围术期应用艾司奥美拉唑合理性有待提高,临床药师应加强临床用药教育以提高合理用药水平。