蛋白激酶C对福尔马林诱导急性内脏炎症疼痛评分的影响

目的 :本实验用福尔马林诱导的急性内脏炎症痛模型 ,经脊髓蛛网膜下腔插管给予蛋白激酶C (PKC)激动剂PMA (phorbol 12 myristate 13 acetate)和抑制剂H 7(1 (5 isoquinolinesulfonyl) 2 methylpiperazinedihydrochloride) ,观察其对内脏炎症痛疼痛评分的影响。方法 :实验选用成年健康Wistar大鼠 ,随机分 5组 :单纯福尔马林直肠致炎组 (F) ;脊髓蛛网膜下腔内插管组 (F IT) ;插管内注射生理盐水组 (F IT NaCl) ;插管内注射PMA组 (F IT PMA) ;插管内注射H 7组 (F IT H 7)。记录 5组大鼠的疼痛行为反应 ,以 15min为一个时间段 ,共记录 8个时间段 ,计 2h ,分别计算疼痛分数。结果 :F组与F IT组 8个时间段内疼痛分数无显著性差异 (P >0 .0 5 ) ;F IT NaCl组与F IT组相比也无显著性意义 ;F IT PMA组与F IT NaCl组相比在前 75min内有显著性差异(P <0 .0 1) ;F IT H 7组与F IT NaCl组相比在前 90min内有显著性差异 (P <0 .0 1或P <0 .0 5 )。结论 :①蛛网膜下腔内插管对内脏疼痛评分无影响 ;②PKC在福尔马林致急性内脏炎症痛感受中起重要作用。     

大鼠福尔马林内脏炎症痛过程中脊髓PKC、PKCε膜转位的变化

目的:初步探讨PKC、PKCε在内脏炎症痛过程中的作用。方法:本实验用福尔马林(F)直肠粘膜下注射的内脏炎症痛模型,经脊髓蛛网膜下腔插管分别给予PKC、PKCε激动剂PMA(phorbol12 myristate13 acetate)和抑制剂H 7(1 (5 isoquinolinesulfonyl)2 methylpiperazinedihydrochloride),结合SDS 聚丙烯酰胺凝胶电泳(SDS PAGE)、蛋白印迹 (Western blot)等生化技术。选用成年健康Wistar大鼠,随机分 4组: 正常对照组N,内脏痛组(F+NaCl),PMA组(F+PMA)和H 7组(F+H 7)。共分福尔马林直肠内致炎后 30min、60min和 120min三个时间段。结果:在福尔马林直肠致炎后 60min内,F+NaCl组与N组PKC、PKCε膜转位相比分别明显增高 (P<0. 01);F+PMA组与F+NaCl组PKC、PKCε相比分别明显增高(P<0. 05);F+IT+H 7组与F+IT+NaCl组PKC、PKCε相比分别明显降低 (P<0. 05 )。结论: 福尔马林致内脏炎症痛过程中PKC、PKCε被激活,提示PKC、PKCε可能参与了内脏炎症痛的发生。     

PKC抑制剂对甲醛诱导的内脏炎性痛大鼠脊髓ERK1/2磷酸化的影响

目的:探讨蛋白激酶C(protein kinase C,PKC)抑制剂H-7对福尔马林诱导的内脏炎症痛大鼠脊髓细胞外调节蛋白激酶1/2(extracellular regulated protein kinases,ERK1/2)磷酸化的影响。方法:清洁级雄性SD大鼠,重200~250 g,随机分为5组:正常对照组(N组);甲醛直肠致炎组(F组);甲醛直肠致炎和脊髓蛛网膜下腔内插管组(IT组);甲醛直肠致炎、脊髓蛛网膜下腔内插管并注射生理盐水组(NaCl组);甲醛直肠致炎、脊髓蛛网膜下腔内插管并注射H-7组(H-7组);每组大鼠24只,共120只。5组大鼠,每组8只,每15 min进行一次疼痛计分,连续记录大鼠的行为120 min;在甲醛造模后30 min、60 min和120 min取出L_6-S_1节段脊髓进行ERK1/2磷酸化检测。结果:F、IT、NaCl组和H-7组大鼠在注射甲醛后30 min均达到疼痛评分的最大值。H-7组在前90 min内疼痛分数显著低于F组(P<0.05或P<0.01)。与N相比,F组甲醛直肠黏膜注射后脊髓ERK1/2磷酸化水平增加,30 min时达最高水平,60 min时仍高于对照组,有显著性差异(P<0.05或P<0.01);与N相比,H-7组甲醛直肠黏膜注射后脊髓ERK1/2磷酸化水平也增加,30 min时达最高水平,60 min时仍高于对照组,有显著性差异(P<0.05或P<0.01);在甲醛注射后60 min内,H-7组与F组相比,ERK1/2磷酸化水平明显下降,有显著性差异(P<0.05或P<0.01)。结论:PKC抑制剂H-7能降低内脏炎症痛疼痛评分和抑制脊髓ERK1/2磷酸化水平,ERK1/2是PKC的下游信号通路在内脏炎症痛发病机制中起重要作用,对内脏炎症痛靶向治疗具有重要意义。     

蛋白激酶C对内脏炎症痛模型大鼠脊髓背角神经元电活动的影响

目的：本实验采用福尔马林诱导的急性内脏炎症痛模型，观察蛋白激酶C（Protein Kinase C，PKC）激动剂PMA（phorbol 12-myristate 13-acetate）与抑制剂H-7（1-（5-isoquinolinesulfonyl）2-meth-ylpiperazine dihydrochloride）对脊髓背角神经元放电的影响。方法：选用健康成年Wistar大鼠，随机分为4组：（1）福尔马林直肠粘膜下注射致炎组（F）；（2）福尔马林致炎与脊髓微透析生理盐水组（F＋NS）；（3）福尔马林致炎与脊髓微透析H-7组（F＋H-7）；（4）福尔马林致炎与脊髓微透析PMA组（F＋PMA）。结果：记录到24个单位的反应结果表明：福尔马林致炎后0～120min内放电频率明显增加，特别是0～15min和15～30min内与致炎前相比均有显著性增强（P＜0．05）；经微透析PMA和H-7后，上述时间段内放电频率分别明显增强（P＜0．01）和回降（P＜0．05）。结论：PKC在福尔马林致内脏炎症痛的产生和维持中起重要作用。     

电针刺激足三里穴对甲醛溶液所致内脏炎症痛大鼠脊髓蛋白激酶C膜转位水平的影响

目的:探讨电针刺激足三里穴对甲醛溶液内脏炎症痛的镇痛作用及对大鼠脊髓蛋白激酶C(Protein kinase C,PKC)膜转位水平的影响。方法:实验随机分为:正常对照组(N);电针组(EA);内脏炎症痛组(VP);电针加内脏炎症痛组(EA+VP),每组大鼠18只。应用甲醛溶液大鼠直肠黏膜下注射复制的内脏炎症痛模型,注射后120 min内观察疼痛反应,15 min为一个观察时间段,计算疼痛评分;注射后30 min、60 min和120 min内取大鼠L_6~S_2阶段脊髓进行PKC膜转位水平检测。结果:VP组大鼠在甲醛溶液注射后,30 min内达疼痛反应的高峰,随后逐渐减轻;EA+VP组大鼠疼痛反应减轻,在前90 min内疼痛分数明显低于VP组,P<0.05或P<0.01。VP组大鼠在甲醛溶液注射后,30 min时PKC膜转位水平明显增加,随后膜转位水平明显降低;EA+VP组大鼠在前60 min内,PKC膜转位水平明显下降,与VP组相比有显著性差异,P<0.05。结论:电针刺激足三里穴明显减轻内脏炎症痛大鼠疼痛反应,可能通过抑制大鼠脊髓PKC膜转位水平起镇痛作用。     

皮内注射对急性内脏炎症痛大鼠的抗伤害效应和对脊髓Fos表达的影响

目的:观察皮内注射对福尔马林诱导的急性内脏炎症痛大鼠是否具有抗伤害效应和对脊髓Fos蛋白表达的影响. 方法:实验选用SD大鼠随机分为7组:单纯福尔马林致炎组(F);0.25%利多卡因实验区皮内注射组(F-0.25%L-IN);0.25%利多卡因实验区外皮内注射组(F-0.25%L-OUT);0.125%利多卡因实验区皮内注射组(F-0.125%L-IN);0.125%利多卡因实验区外皮内注射组(F-0.125%L-OUT);生理盐水实验区皮内注射组(F-S-IN);生理盐水实验区外皮内注射组(F-S-OUT).对各组大鼠分别进行疼痛学评分,每15min为一个时间段,共4次,1h后取出S1脊髓节段以免疫组化法检测FLI阳性神经元. 结果:各组在第一个时间段内疼痛学评分差异无显著性(P＞0.05);在第三、第四个时间段内F组和F-0.25%L-IN、F-0.25%L-OUT、F-S-IN组相比疼痛学评分差异有显著性(P＜0.01)而和F-0.125%L-IN、F-0.125%L-OUT、F-S-OUT相比疼痛学评分差异无显著性(P＞0.05);脊髓Fos阳性神经元数量在F-0.25%L-IN、F-0.25%L-OUT、F-S-IN组均显著减少(P＜0.01). 结论:Fos阳性神经元可能参与了化学性致痛信息的传导和调控.     

蛋白激酶C在甲醛复制内脏炎症痛大鼠脊髓背角神经元电活动中的作用

目的:观察蛋白激酶C抑制剂氯丙嗪对甲醛复制的内脏炎症痛大鼠脊髓背角神经元电活动的影响,了解蛋白激酶C在甲醛复制的内脏炎症痛中的作用。方法:实验于2005-01/11在泰山医学院基础医学研究所完成。选用24只健康成年Wistar大鼠,数字表法随机分为3组(n=8):①甲醛组:体积分数为0.05的甲醛100μL直肠黏膜下注射致炎,复制内脏炎症痛模型。②甲醛 生理盐水组:在脊髓背角找到对直肠刺激敏感的神经元后,腹腔注射生理盐水0.4mL/kg,30min后记录前对照反应,然后行甲醛直肠黏膜下致炎,方法和剂量同甲醛组。③甲醛 氯丙嗪组:腹腔注射25g/L氯丙嗪0.4mL/kg,其余处理同甲醛 生理盐水组。记录3组大鼠注射甲醛后120min内脊髓背角神经元放电频率的变化,以15min为一个时间段,共记录8个时间段。以给药前神经元的放电频率为参照,计算给药后反应的相对值(给药后实际反应频率/给药前实际反应频率×100%)。结果:24只大鼠全部进入结果分析,共记录到24个单位的反应结果。①甲醛组在给药后0～15min和16～30min时间段的放电频率分别为致炎前基线水平的(283.7±46.0)%和(254.0±37.4)%,与致炎前相比均有显著性增加(P<0.05)。②甲醛 氯丙嗪组在致炎后0～15min和16～30min两时间段的脊髓背角神经元放电频率分别为基线水平的(124.6±10.25)%和(105.4±8.69)%;甲醛 生理盐水组致炎后同时间段的放电频率为基线水平的(279.7±37.4)%和(249.2±38.5)%。甲醛 氯丙嗪组在致炎后0～15min和16～30min两时间段的放电频率低于其他2组(P<0.05),另2组比较差异不显著(P>0.05)。结论:①甲醛直肠黏膜下注射可稳定复制大鼠炎症性内脏痛模型。②蛋白激酶C抑制剂氯丙嗪可使脊髓背角神经元放电频率减少,提示蛋白激酶C参与甲醛诱导急性炎症引起的痛觉敏感化的形成。     

舒芬太尼对福尔马林痛小鼠的镇痛作用及其对血液中IL-6和IL-10的影响

目的:研究舒芬太尼对福尔马林致痛小鼠细胞因子IL-6,IL-10的变化,以进一步探讨舒芬太尼对镇痛及细胞因子平衡的影响。方法:选择97只昆明清洁级小鼠随机分四组,完全空白对照组(7只)、假给药组(C组,n=30)、舒芬太尼组(S组,n=30)、芬太尼组(F组,n=30)。C、S、F组右后脚趾部皮下注射3%福尔马林0.05ml致痛,在此基础上腹腔分别注射生理盐水0.3ml,舒芬太尼0.05mg/kg,芬太尼0.2mg/kg,25min后记录注射福尔马林后0～5min(Ⅰ相)和15～60min(Ⅱ相)的疼痛反应评分及在注射药物后1h、3h、6h、9h、12h和24h检测血液中IL-6,IL-10水平变化。结果:舒芬太尼抑制福尔马林Ⅰ相和Ⅱ相痛反应(P<0.05)。在Ⅰ相痛反应中,S组和F组比较有显著差异(P<0.05);C、S、F组IL-6含量明显高于完全空白对照组,C组在3小时达峰值,而S组和F组6小时达峰值;S组和F组的IL-10含量明显高于C组和空白对照组(P<0.05),S组和F组之间无统计学意义(P>0.05)。结论:在福尔马林致痛模型中,舒芬太尼起效快,镇痛作用强,延迟IL-6的分泌,促进IL-10分泌,通过有效的镇痛维持细胞因子的平衡。     

鞘内预注布托啡诺与吗啡对炎性痛大鼠痛觉及脊髓c-fos蛋白表达的影响

目的观察鞘内预先注射布托啡诺与吗啡对福尔马林诱导的炎性痛大鼠疼痛行为学及脊髓c-fos蛋白表达的影响。方法大鼠被随机分为布托啡诺组、吗啡组及对照组,每组8只。布托啡诺组鞘内预先注射布托啡诺10μg,吗啡组鞘内预先注射吗啡10μg,对照组鞘内预先注射0.9%氯化钠注射液,然后在三组大鼠的左后足掌面皮下注射福尔马林致痛,观察各组大鼠行为学变化并通过免疫组化法测定大鼠腰4~6节段脊髓背角c-fos受体的表达。结果与对照组比,吗啡组和布托啡诺组没有明显的福尔马林致痛双相反应,且福尔马林致痛大鼠腰4-6脊髓背角浅层及深层fos样免疫反应神经元(FLIN)数量明显减少(q分别=5.65、4.78;5.85、6.27,P均<0.05),而与吗啡组比较,布托啡诺组大鼠行为学表现更安静,疼痛加权评分减低,脊髓背角浅层及深层FLIN数量也明显减少(q分别=9.53、6.37,P均<0.05)。结论鞘内预先注射布托啡诺与吗啡能够对福尔马林致痛大鼠产生明显的抗伤害和镇痛作用,且布托啡诺的镇痛效果优于吗啡。     

星状神经节阻滞对炎症痛兔血清皮质醇和白介素-8的影响

目的研究星状神经节阻滞(SGB)对福尔马林诱导的兔伤害反应、血清皮质醇(CS)和白介素8(IL8)的影响。方法用手术法在兔星状神经节附近置入导管,选择24只随机分为三组假手术组(A组)、SGB组(B组)和对照组(C组)。B和C组在右前肢足底皮下注射3%福尔马林0.5ml致痛,A组同样部位注射等量生理盐水。致痛前10min,B组经导管注射0.25%布比卡因0.5ml,A和C组注射等量生理盐水。致痛前10min(T0)、致痛后10(T1)、60(T2)和120min(T3)取静脉血,放免法测血清CS和IL8浓度。结果SGB后福尔马林诱导的Ⅱ期伤害反应明显缓解。C组致痛后血清CS浓度显著升高,在T2时点达高峰(P<0.01);B组致痛后血清CS浓度无明显升高(P>0.05),与C组比有显著性差异(P<0.05)。B组和C组T2和T3时点血清IL8浓度较T0及T1时点显著升高(P<0.01);B组T2和T3时点血清IL8浓度明显低于C组同时点(P<0.01)。结论SGB可减轻福尔马林诱导的Ⅱ期伤害反应,可抑制福尔马林刺激引起的血清CS和IL8浓度升高,这些改变可能与其治疗炎症痛机制有关。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Clinical Trial Updates and Hotline Sessions presented at the European Society of Cardiology Congress 2007

This article provides information and commentaries on trials which were presented at the Hotline and Clinical Trial Update Sessions at the European Society of Cardiology Congress 2007 in Vienna. The key presentations were performed by leading experts in the field with relevant positions in the trials or registries. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information of relevant publications.     

Balance and Boundaries in Grief Counseling: An Intervention Framework for Volunteer Training

Volunteers or paraprofessional counselors are commonly used to provide supportive care to the bereaved. These counselors generally are trained in basic listening skills, providing a generic, nonspecific approach to intervention that remains to be proven effective. The present paper outlines a framework that provides paraprofessionals with a broader model for intervention with the bereaved. Attention to boundaries as a helper and balance in the grief recovery are central to the model. Interventions are described that provide the paraprofessional counselor with more options for tailoring their counseling strategy to the individual. These include techniques that are presumed to be more specific to the enhancement of grief recovery.     

A new method for the simultaneous analysis of unmodified and modified urinary nucleosides and nucleobases by high performance liquid chromatography

Details are given of a new, rapid and simple pre-fractionation method and an isocratic high performance liquid chromatography system suitable for parallel analysis of nucleosides and nucleobases from urine and other biological fluids. The quantitative recovery and excellent reproducibility of the method is demonstrated by analysis of representative standard RNA catabolites. The advantage of this new method for application to biological samples is discussed.     

Adsorption of Charged Non-albumin Bound Drugs by Amorphous Silica

We investigated the in vitro drug adsorption of PQ 10150 sodium silicate gel (AIS, Santa Clara, CA) with particle size of 230 um and surface area of 400 nr/g. We observed 99% to 88% adsorption of gentamicin; a mean 91 % of disopyramide; a mean 89% of quinidine at low concentration, falling to 75% at higher concentration. Insulin was 88% adsorbed at low concentrations but less so (65%) at higher concentrations. We observed a mean 83 % adsorption of procainamide, a mean 84% of N-acetyl procainamide, 74% oflidocaine, 73% of amitriptyline; and 44% of desipramine. We found an average 14% reduction of total digoxin concentration when serum containing digoxin (2 to 33 ng/mL) was exposed to sodium silicate, while the reduction in free digoxin concentration was 16%. Five percent ethosuximide was also removed. The adsorption of theophylline, phenobarbital, acetaminophen, phenytoin, ethylene glycol, methotrexate, salicylate, thiocyanate and diazepam was minimal and not significant. We conclude that significant amounts of charged, non-albumin bound drugs can be removed by PQ 10150 sodium silicate gel.