雄激素受体在乳腺癌细胞中的表达及其对细胞增殖的影响

目的 检测雄激素受体(AR)在乳腺癌细胞中的表达,并观察雄激素刺激对乳腺癌细胞增殖的影响.方法 选择雌激素受体(ER)阳性的MCF-7和ER阴性的MDA-MB-453乳腺癌细胞,体外培养,Western blot技术检测两乳腺癌细胞株中AR蛋白的表达,MTT法检测用1×10-7、1×10-8和1×10-9 mol/L不同浓度的雄激素二氢睾酮(DHT)分别干预48、96、144 h后的细胞增殖,并应用流式细胞术检测DHT刺激乳腺癌细胞72 h后细胞周期的变化.结果 两个乳腺癌细胞株经DHT作用后AR蛋白表达均增多,DHT通过AR抑制MCF-7和MDA-MB-453两个乳腺癌细胞株的生长,各时间段不同浓度组比较A值差异无统计学意义(P＞0.05),细胞周期结果显示G1期细胞比例增高,S期细胞比例降低.结论 雄激素受体途径对ER阳性的MCF-7和ER阴性的MDA-MB-453乳腺癌细胞均有抑制生长作用,可能通过抑制细胞由G1期到S期转化来实现的.

Abstract：

Objective To evaluate the expression of androgen receptor (AR) in the breast cancer cell lines and its effect on proliferation of breast cancer cells. Methods The estrogen receptor (ER) -positive MCF-7 and ER-negative MDA-MB-453 cells were involved in this study and cultured in vitro. The expression of AR was detected by using Western blotting. Cell proliferation was determined by methyl thiazol tetrazolium (MTT) assay after the treatment with different concentrations of dihydrotestosterone (DHT) ( 1 x 10 -7, 1 x 10- 8, 1 x 10 -9 mol/L) for 48, 96 and 144 h respectively. Cell cycle was analyzed by flow cytometry following culture for 72 h. Results DHT increased the AR expression in the two breast cancer cell lines. AR pathway could inhibit proliferation of MCF-7 and MDA-MB-453 cells. There was no significant difference in absorbance values among three treatment groups at different time points (P ＞ 0. 05). Cell cycle analysis revealed that the proportion of cells at G1 phase was increased, and that at S phase decreased. Conclusion AR pathway may inhibit proliferation of ER-negative MDA-MB-453 breast cells as well as ER-positive MCF-7 cells, by suppressing the process of G1 to S phase progression.     

分化和DNA结合抑制因子1基因对乳腺癌细胞株MCF-7增殖活性及分泌血管内皮生长因子的影响

目的 观察分化和DNA结合抑制因子1(Id1)基因对人乳腺癌细胞增殖活性以及分泌血管内皮生长因子(VEGF)能力的影响.方法 将正义、反义Id1基因真核表达载体以及空载体分别转染乳腺癌MCF-7细胞株,经潮霉素筛选获得稳定细胞株;逆转录-聚合酶链反应(RT-PCR)和免疫细胞化学染色检测Id1 mRNA及Id1蛋白、VEGF蛋白表达;细胞计数、噻唑蓝(MTT)比色法及流式细胞仪检测细胞增殖活性及细胞周期;酶联免疫吸附试验( ELISA)检测细胞上清液中VEGF浓度.结果 与空载体转染细胞比较,转染正义Id1载体的MCF-7细胞中Id1 mRNA和Id1蛋白、VEGF蛋白表达水平上调,细胞生长加速(P＜0.05);而反义Id1载体转染组细胞Id1、VEGF表达下降,细胞增殖速度降低(P＜0.05).流式细胞检测结果显示,正义Id1转染组增殖期细胞(S+G2+M)比例为(48.45 ±2.97)％,空载体组为(32.40±0.49)％,反义Id1组为(23.08±1.56)％,各组间差异有统计学意义(P＜0.01);3组细胞凋亡指数分别为(3.26±1.28)％、(7.42±1.04)％和(11.83 ±1.59)％,组间差异有统计学意义(P＜0.01);正义Id1转染组细胞上清液中VEGF浓度较空载体组显著增高(P＜0.01),反义Id1组VEGF分泌量则较空载体组显著降低(P＜0.05).结论 Id1基因与乳腺癌MCF-7细胞增殖活性、细胞周期调控及VEGF分泌能力相关.     

锤头型核酶特异性阻断雄激素受体表达对前列腺癌细胞生长的影响

目的：探讨核酶阻断雄激素受体（AR）基因表达治疗前列腺癌的可能性。方法：在脂质体介导下，锤头型抗雄激素受体核酶表达载体转染前列腺癌细胞，采用逆转录－聚合酶链反应（RT－PCR）检测ARmRNA，四甲基偶氮唑盐（MTT）法检测细胞增殖活性，流式细胞仪（FCM）检测细胞周期时相，原位末端转移酶标记法检测细胞凋亡。结果：核酶表达载体转染1－5d后，前列腺癌细胞AR mRNA水平降低32．6％－40．7％（P＜0．05），细胞生长抑制率18．28％－35．34％（P＜0．05），细胞周期阻滞于G2／M期，诱导细胞凋亡，细胞凋亡比率增加20．70％（P＜0．01）。结论：应用核酶特异性切割ARmRNA，能有效阻断AR基因的表达，诱导前列腺癌细胞凋亡，有可能成为前列腺癌基因治疗的有效方法之一。     

p21waf1基因转染对乳腺癌细胞中心体复制和增殖活性的影响

目的 观察p21waf1基因转染对人乳腺癌细胞增殖活性和中心体复制的影响.方法 应用脂质体介导法将pIRES-p21waf1真核表达载体转染人人乳腺癌细胞系MCF-7,MTF法检测细胞增殖,流式细胞仪检测细胞周期分布,免疫荧光技术检测乳腺癌细胞的中心体复制情况.结果 p21waf1基因转染后乳腺癌细胞生长显著受抑制,细胞周期停滞于G1期,转染组G1期、S期和G2/M期细胞比例分别为(70.52±3.21)%、(16.38 4±1.17)%、(9.42 ±0.98)%,未转染组则为(49.84±1.58)%、(36.83±1.36)%、(15.64±1.09)%,两者比较差异有统计学意义,P值分别《0.01、《0.05、《0.05.中心体复制异常的乳腺癌细胞数较转染前明显减少(P《0.01).结论 p21waf1基因转染能够抑制人乳腺癌细胞增殖和中心体的异常复制,进而阻止乳腺癌的发生发展,可能成为乳腺癌治疗的一种新手段.     

雄激素对MCF-7乳腺癌细胞株增殖凋亡的影响

目的 观察睾丸酮对MCF-7乳腺癌细胞株增殖、凋亡的影响,并探讨其机制.方法 将1×10~(-5)、1×10~(-7)、1×10~(-9)、1×10~(-11) mol/L的睾丸酮分别作用于乳腺癌MCF-7细胞24、48、72 h,噻唑蓝(MTT)比色法检测细胞生长,流式细胞术检测不同浓度睾丸酮作用48 h时MCF-7细胞的周期分布和凋亡以及该细胞株中细胞周期素D1蛋白和雄激素受体的表达.结果 高浓度睾丸酮抑制MCF-7乳腺癌细胞株的增殖,1×10~(-5) mol/L睾丸酮作用48 h时,细胞生长抑制率为22.21%,细胞凋亡率为(58.60±5.41)%,但可使细胞周期由G_1 期进入S期,并可使细胞周期素D1蛋白表达量增加,雄激素受体蛋白表达量下降.低浓度睾丸酮(1×10~(-9) mol/L)作用后细胞周期素D1蛋白表达量无明显变化,雄激素受体蛋白表达量升高,在短时间内(24 h)可促进MCF-7细胞增殖.结论 高浓度睾丸酮在体外可使MCF-7乳腺癌细胞株细胞周期素D1蛋白表达增加,使细胞周期由G_1进入S期,而同时促使细胞凋亡,表现出抗肿瘤作用.低浓度睾丸酮有短暂的促进MCF-7乳腺癌细胞增殖的作用.     

过表达核心蛋白聚糖基因对胆管癌细胞周期及凋亡的影响

目的 观察过表达核心蛋白聚糖(DCN)基因对胆管癌细胞周期及凋亡的影响.方法 脂质体介导真核表达质粒pEGFP-DCN和空载体pEGFP-N1转入人胆管癌细胞株QBC939,Westernblot检测DCN蛋白的表达,实时定量反转录-聚合酶链反应(RT-qPCR)检测DCN mRNA的表达,克隆形成实验计算克隆形成率,噻唑蓝(MTT)法检测细胞增殖活力,流式细胞术检测细胞周期及凋亡.结果 RT-qPCR示过表达DCN相对空载体上调32.34倍;Western blot结果示过表达组DCN上调2.00倍.pEGFP-DCN转染组细胞克隆形成数[(210.9±19.3)个]显著低于空质粒转染组[(608.7±56.3)个],差异有统计学意义(P＜0.05).转染pEGFP-DCN细胞与空载体比较,细胞增殖能力显著降低,差异有统计学意义(P＜0.05).流式细胞周期检测显示,胆管癌细胞转染pEGFP-DCN后G1～ Go期细胞比例明显升高,而G2～S期细胞减少,细胞周期被阻滞在G1～Go期,凋亡分析转染pEGFP-DCN的QBC939细胞较转染空载体细胞凋亡显著增加,半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3明显增高,而B细胞淋巴瘤/白血病-2(bcl-2)的表达水平明显降低(0.787±0.068比1.276±0.157).结论 转染DCN能够显著抑制胆管癌细胞的增殖,明显促进胆管癌细胞凋亡,而DCN促进胆管细胞凋亡与上调Caspase-3和下调bcl-2蛋白相关.     

反义寡核苷酸阻断雄激素受体表达对前列腺癌细胞生长活性的影响

目的　探讨反义技术阻断雄激素受体 (AR)基因表达对前列腺癌细胞生长的影响。　方法　设计、合成针对AR基因反义寡核苷酸 (ASODN) ,在脂质体介导下转染前列腺癌细胞。采用RT PCR方法检测AR基因表达 ;MTT比色法检测细胞增殖活性 ;透射电镜、TUNEL检测细胞凋亡 ;流式细胞术分析细胞周期时相。　结果　 0 .5～ 2 .0 μmol LASODN作用 12～ 36h ,癌细胞ARmRNA水平降低 10 .45 %～ 82 .10 %(P <0 .0 5 ) ,细胞增殖活性抑制 11.8%～ 5 6 .9%(P <0 .0 5 ) ,细胞周期阻滞于G2 M期 ,部分细胞呈现典型凋亡形态学改变 ,凋亡比率为 34.2 5 %(P <0 .0 1)。　结论　应用ASODN封闭AR基因表达能抑制前列腺癌细胞体外生长活性 ,有望成为前列腺癌基因治疗的有效策略。     

酪蛋白激酶2抑制剂降低前列腺癌雄激素受体功能和细胞增殖

目的 观察人工合成酪蛋白激酶2(CK2)选择性抑制剂四溴肉桂酸(TBCA),对各种前列腺癌细胞株雄激素受体(AR)反式激活、细胞增殖和活力的效应.方法 TBCA和基因特异性小干扰RNA(siRNA)应用到前列腺癌细胞株,Alamar blue法检测细胞生长,流式细胞术检测细胞周期分布,荧光素酶基因报道分析检测AR反式激活,免疫荧光法检测AR核定位以及定量聚合酶链反应(PCR)检测AR介导的基因表达.结果 TBCA呈剂量依赖性抑制细胞增殖和细胞周期停滞在G2/M期,半抑制浓度值(IC50)为25 mol/L.TBCA阻断AR核转位和基因表达(P＜0.01).2种CK2催化亚单位都参与雄激素刺激的核转位和AR介导的基因表达(P＜0.05).结论 CK2α和CK2α’亚单位都参与了AR信号转运表达,TBCA有可能成为一种有效的前列腺癌化学治疗药物.     

小干扰RNA抑制雄激素受体基因表达对人膀胱癌T24细胞增殖及凋亡的影响

目的 观察小干扰RNA技术(siRNA)抑制雄激素受体(AR)基因的表达对人膀胱癌T24细胞增殖及凋亡的影响.方法 化学合成针对AR的siRNA,用脂质体转染T24细胞.采用实时荧光定量逆转录-聚合酶链反应(RT-PCR)和Western blot检测AR mRNA和蛋白的变化.转染细胞48 h后用噻唑蓝(MTT)比色法检测细胞体外增殖活性的变化,流式细胞术检测细胞的凋亡状况.结果 成功的转染T24细胞,实时荧光定量RT-PCR筛选出一条AR mRNA抑制效率最高的siRNA,行Western blot检测可抑制AR蛋白表达至70.3%.转染细胞48 h后,T24细胞增殖活性抑制率达到(25.9±5.4)%,细胞凋亡率达到21.61%.结论 应用siRNA干扰技术能有效的抑制AR基因的表达,同时可抑制人膀胱癌T24细胞的体外增殖活性及促进其凋亡的发生.     

miR-9-5p调控雄激素受体的表达促进卵巢颗粒细胞增殖

目的分析微小RNA-9-5p(miR-9-5p)在多囊卵巢综合征(PCOS)中的诊断价值,并探讨对卵巢颗粒细胞(KGN)增殖的作用机制。方法采用荧光定量PCR(qRT-PCR)技术分析miR-9-5p在50例PCOS患者(实验组)及50例健康女性(对照组)血清中的表达特征。采用受试者工作特征曲线(ROC)评估miR-9-5p在诊断PCOS中的曲线下面积(AUC)、特异度及敏感度。培养KGN细胞并分为空白组、阴性转染组及转染组,分别采用MTT及流式细胞技术检测干扰miR-9-5p后KGN增殖和细胞周期的变化。利用双荧光素酶报告基因实验检测miR-9-5p对雄激素受体(AR)的直接调节作用。采用western blot技术分析干扰miR-9-5p后KGN中AR蛋白表达水平的变化。结果与对照组相比,miR-9-5p在PCOS患者血清中的表达显著升高(P<0.05)。ROC显示,miR-9-5p在诊断PCOS中AUC为0.76,敏感性为65.43%,特异性为74.09%。与空白及阴性转染组相比,转染拮抗剂后KGN中miR-9-5p表达水平显著降低(P<0.05)。干扰miR-9-5p显著降低KGN增殖(P<0.05),并抑制细胞周期G1到S期的转变,表现为G0/G1期细胞比例增加,而S期细胞比例减少。双荧光素酶报告基因实验显示,AR是miR-9-5p的靶基因,miR-9-5p可直接与AR mRNA 3’-非编码区互补结合而降低KGN中AR蛋白的表达水平。结论miR-9-5p在PCOS患者血清中表达上调,并可能是一种新的PCOS诊断标志物。在机制上,miR-9-5p通过直接调控AR而促进KGN增殖。     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Utilisation des médicaments prokinétiques en réanimation : indications et limites ?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.