CD4+CD25+调节性T细胞/辅助性T细胞17在脓毒症大鼠中的作用

目的 观察CD4+ CD25+调节T细胞(Treg)/辅助性T细胞17(Th17)细胞在脓毒症大鼠炎性免疫反应中的作用.方法 110只雄性SD大鼠随机分为正常对照组、假手术组、脓毒症(CLP)组,采用改良的盲肠结扎穿孔术(CLP)制作大鼠脓毒症模型.采用流式细胞术检测CD14+单核细胞表面人类白细胞抗原-DR基因(HLA-DR)表达率、Treg细胞及TH17细胞比例;酶联免疫吸附试验(ELISA)检测白细胞介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β、白细胞介素(IL)-17炎性因子蛋白表达.结果 与假手术组比较:(1)伴随着脓毒症病情的发展,大鼠出现明显的免疫抑制,CD14+单核细胞HLA-DR表达率＜30％,IL-10/TNF-α比值(27.41 ±7.04比6.63 ±2.60)明显增高(P＜0.01).(2)术后96 h脓毒症大鼠Treg细胞[(11.91±3.88)％比(6.57±2.60)％,P＜0.01]和Th17细胞[(5.14±0.29)％比(2.85±0.07)％,P＜0.01]表达明显增高.(3)术后96 h脓毒症组前炎性细胞因子IL-6[(42.31±15.89) ng/L比(6.32 ±3.18) ng/L,P＜0.01]、IL-10[(69.89 ±20.78) ng/L比(13.58±5.37) ng/L,P＜0.01]、TNF-α[(5.03±3.10) ng/L比(2.77±1.10) ng/L,P＜0.01]、TGF-β[(4.99±2.01) ng/L比(1.88±1.07) ng/L,P＜0.01]、IL-17[(92.77±11.64) ng/L比(7.58±2.30) ng/L,P＜0.01]表达明显增高.结论 伴随着脓毒症病情的发展,大鼠出现明显的免疫抑制;在大鼠脓毒症的发生发展中,Treg细胞介导的免疫抑制及Th17细胞介导免疫激活反应同时存在;脓毒症细胞因子微环境变化可能是导致Treg细胞/Th17细胞失衡的原因之一.     

血清IL-9、IL-18及IL-32水平对多发性骨髓瘤患者肾损伤的诊断价值

目的探讨多发性骨髓瘤(multiple myeloma, MM)患者血清白细胞介素-9(interleukin-9,IL-9)、白细胞介素-18(interleukin-18,IL-18)及白细胞介素-32(interleukin-32,IL-32)的表达及其预测肾损伤的价值。方法选取2016年1月至2019年12月我院收治的78例MM患者,依据国际分期系统(International Staging System, ISS)分为I期(n=15)、Ⅱ期(n=26)和Ⅲ期(n=37),根据肾功能情况,将其分为肾损伤组(n=28)和无肾损伤组(n=50)。另选取同期50例正常者作为对照组。检测各组血清IL-9、IL-18、IL-32及β_2-微球蛋白(β_2-microglobulin,β_2-MG)水平。应用受试者工作特征(receiver operating characteristic, ROC)曲线分析血清IL-9、IL-18、IL-32及β_2-MG水平诊断MM患者肾损伤的价值。采用Pearson相关分析MM患者血清IL-9、IL-18、IL-32水平与β_2-MG的相关性。结果 MM组与对照组相比血清IL-9[(63.15±18.36)ng/L比(22.78±7.15)ng/L]、IL-18[(580.64±70.35)ng/L比(174.30±26.82) ng/L]、IL-32[(817.62±112.36)ng/L比(260.85±34.70)ng/L]及β_2-MG[(6.50±2.52)mg/L比(1.66±0.58)mg/L]水平均明显高于对照组(P0.01)。随着ISS分期的增加,MM患者血清IL-9、IL-18、IL-32及β_2-MG水平增加(P0.01)。肾损伤组与无肾损伤组相比,血清IL-9[(91.26±19.42)ng/L比(45.30±14.20)ng/L]、IL-18[(812.46±95.27)ng/L比(407.28±53.60)ng/L]、IL-32[(1130.85±154.70)ng/L比(604.20±71.38)ng/L]及β_2-MG[(10.18±4.75)mg/L比(3.15±1.06)mg/L]水平均明显高于无肾损伤组(P0.01)。ROC曲线分析显示,IL-9、IL-18、IL-32及β_2-MG四项联合诊断MM患者发生肾损伤的曲线下面积(0.963,95%CI:0.905～0.997)最大,其灵敏度和特异度为98.6%和81.2%。相关分析显示,MM患者血清IL-9、IL-18、IL-32与β_2-MG均呈正相关(P0.01)。结论血清IL-9、IL-18、IL-32水平在MM患者中明显升高,且与MM患者的病情分期及肾损伤有关,联合β_2-MG检测对诊断MM患者发生肾损伤具有良好价值。     

透析膜对血液透析患者外周血转化生长因子β1及单核细胞趋化蛋白-1水平的影响

目的研究不同透析膜对维持性血液透析(MHD)患者外周血转化生长因子β1(TGP-β1)及单核细胞趋化蛋白-1(MCP-1)水平的影响.方法应用酶联免疫法(ELISA)测定长期用铜仿膜(CU)和聚砜膜(PSU)透析患者外周血TGF-β1及MCP-1水平.结果与正常对照组[(50.2±5.7)ng/ml]相比,CU[(82.9±9.8)ng/ml]和P5U[(65.5±9.2)ng/ml]透析患者外周血TGF-β1水平明显增加(P＜0.01,P＜0.05),但PSU组与CU组相比,外周血TGF-β1水平明显下降(P＜0.05).MHD患者外周血MCP-1水平也有所增加,其中PSU组[(72.2±5.3)pg/ml]与对照组[(56.4±7.8)ng/ml]相比有显著性差异(P＜0.05).另外,CU与PSU组内TGF-β1与MCP-1水平之间均呈明显负相关(r=-0.5425与-0.4562,P均＜0.05).结论MHD可增加尿毒症患者TGF-β1与MCP-1水平,但透析膜类型对它们的影响有所不同.     

半胱氨酰天冬氨酸特异性蛋白酶-1抑制剂VX-765对急性胰腺炎的保护作用及其机制

目的探讨半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-1抑制剂VX-765对急性胰腺炎的保护作用及其分子机制。方法将60只SD大鼠(2019年8月购自河南省实验动物中心)按照随机数字表法分为假手术组、模型组和VX-765组,模型组和VX-765组经手术注射5%牛黄胆酸钠制备急性胰腺炎模型,对照组只进行手术不注射5%牛黄胆酸钠。建模24 h后对照组和模型组大鼠经腹腔注射生理盐水,VX-765组大鼠经腹腔注射50 mg/kg VX-765,治疗48 h后,观察3组大鼠存活率,采用自动生化仪检测血清淀粉酶活性;采用苏木精-伊红(HE)染色观察胰腺病理学变化;采用荧光定量聚合酶链反应(PCR)和酶联免疫吸附试验(ELISA)分析3组大鼠外周血白细胞介素(IL)-1β和IL-18 mRNA和蛋白表达水平,计量资料比较采用单因素方差分析。结果VX-765组大鼠血清淀粉酶活性[(1530.40±280.45)U/L]低于模型组血清淀粉酶活性[(2910.43±429.12)U/L],差异有统计学意义(t=4.891,P<0.05)。VX-765组大鼠病理学评分(4.09±0.17)分低于模型组大鼠病理学评分(9.56±2.61)分,差异有统计学意义(t=3.018,P<0.05)。VX-765组大鼠胰腺组织中IL-1β和IL-18 mRNA表达水平(1.96±0.14、1.47±0.17)低于模型组大鼠胰腺组织中IL-1β和IL-18 mRNA表达水平[(3.18±0.21)、(2.67±0.17)],差异有统计学意义(t=2.999、2.104,P<0.05)。VX-765组大鼠外周血清IL-1β和IL-18水平[(159.43±7.09)、(99.50±5.09)ng/L]低于模型组大鼠外周血清IL-1β和IL-18水平[(310.48±25.55)、(190.65±10.43)ng/L],差异有统计学意义(t=2.801、2.466,P<0.05)。结论VX-765通过抑制Caspase-1活性,降低IL-1β和IL-18等炎性因子水平,进而缓解急性胰腺炎。     

乌司他丁对大鼠机械通气肺损伤时γ-氨基丁酸信号通路的影响

目的探讨乌司他丁对大鼠机械通气引起的呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)时γ-氨基丁酸(GABA)信号通路的影响。方法选取健康成年雄性Wister大鼠36只,采用随机数字表法分为三组:正常对照组(C组)、机械通气肺损伤组(VILI组)和机械通气肺损伤+乌司他丁处理组(UTI组),每组12只。VILI组与UTI组采用VT40ml/kg机械通气4h的方法制备大鼠VILI模型。机械通气前1h,UTI组腹腔注射乌司他丁1×10~5 U/kg,C组和VILI组给予等容量生理盐水。收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),检测BALF中白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的浓度;取肺组织,检测湿/干重比(W/D)、肺组织IL-1β、TNF-α和ICAM-1 mRNA的表达;采用免疫组化与Western blot法检测肺组织GAD与GABAA受体的表达量,观察病理学结果并进行肺损伤评分。结果与VILI组比较,UTI组W/D(6.7±2.4vs.8.5±2.3)、肺损伤评分[(6.9±2.3)分vs.(11.8±2.7)分]明显降低(P0.05);BALF中IL-1β[(56±11)ng/L vs.(77±15)ng/L]、TNF-α[(105±29)ng/L vs.(158±37)ng/L]及ICAM-1[(205±46)ng/L vs.(293±61)ng/L]浓度明显降低(P0.05);肺组织IL-1β(1.81±0.26vs.2.58±0.34)、TNF-α(1.61±0.15vs.2.94±0.27)、ICAM-1(1.74±0.27vs.2.79±0.31)mRNA表达量明显降低(P0.05);GAD(0.44±0.08vs.0.18±0.04)和GABAA(0.30±0.09vs.0.15±0.04)受体表达量明显增加(P0.05)。结论乌司他丁可减轻大鼠机械通气引起的呼吸机相关性肺损伤,其机制可能与激活γ-氨基丁酸信号通路有关。     

磷霉素氨丁三醇散对慢性细菌性前列腺炎模型大鼠前列腺组织TNF-α、IL-8、IL-6含量的影响

目的:探讨磷霉素氨丁三醇散(FT)对慢性细菌性前列腺炎模型大鼠肿瘤坏死因子-α(TNF-α)、白介素8(IL-8)、白介素6(IL-6)表达水平的影响。方法:70只雄性SD大鼠随机分为7组,每组10只。A组:假手术组;B组:模型对照组;C组:阳性对照组[左氧氟沙星:100 mg/(kg·d),30 d];D组:FT低剂量、14 d疗程组[200 mg/(kg·d),14 d];E组:FT低剂量、7 d疗程组[200 mg/(kg·d),7 d];F组:FT高剂量、14 d疗程组[300 mg/(kg·d),14 d];G组:FT高剂量、7 d疗程组[300 mg/(kg·d),7 d],各组均采用灌胃给药。实验结束后留取各组大鼠前列腺组织,制作病理切片并使用酶联免疫吸附实验(ELISA)检测各组大鼠前列腺组织匀浆中TNF-α、IL-8、IL-6的含量。结果:与空白对照组比较,模型组大鼠前列腺组织匀浆中的TNF-α、IL-8、IL-6含量均明显升高,差异均有统计学意义[(19.83±6.1)ng/g prot vs(32.93±6.21)ng/gprot,(8.26±0.52)ng/g prot vs(16.2±2.84)ng/g prot,(1.55±0.11)ng/g prot vs(2.51±1.06)ng/g prot,P0.05或0.01];与模型组[(32.93±6.21)ng/g prot、(16.2±2.84)ng/g prot]相比,各治疗组大鼠前列腺组织匀浆中的TNF-α、IL-8含量[(20.54±5.78)ng/g prot、(21.95±6.48)ng/g prot、(23.8±6.93)ng/g prot、(19.97±2.58)ng/g prot、(21.97±3.38)ng/g prot;(12.43±3.64)ng/g prot、(11.11±2.86)ng/g prot、(12.43±4.02)ng/g prot、(8.83±1.32)ng/g prot、(12.68±1.97)ng/g prot]明显降低,差异具有统计学意义(P0.05或0.01);各治疗组大鼠前列腺组织匀浆的TNF-α、IL-8、IL-6含量与阳性对照组比较差异均无统计学意义(P0.05);F组大鼠前列腺组织匀浆中的IL-6的表达量较模型组显著减少[(2.51±1.06)ng/g prot vs(1.76±0.46)ng/g prot,P0.05],其余治疗组及阳性对照组前列腺组织匀浆中的IL-6的表达与模型组比较均无显著性差异(P0.05),但较模型组均有下降趋势。结论:FT通过抑制TNF-α、IL-8、IL-6的表达,减轻前列腺组织的炎症反应,达到治疗大鼠CBP的目的,为临床研究提供了实验依据。     

Nod样受体家族3抑制剂CY-09对大鼠急性胰腺炎的保护作用及机制

目的探讨Nod样受体家族3(NLRP3)抑制剂CY-09对大鼠急性胰腺炎(AP)的保护机制。方法60只购自河南实验动物中心的远交群大鼠随机数字表法分为对照组、模型组和治疗组,每组20只。模型组和治疗组大鼠采用2%牛磺酸胆酸钠建立AP模型,对照组不做AP模型。建模后治疗组经腹腔注射CY-0950 mg/kg;模型组和对照组经腹腔注射等体积生理盐水。治疗24 h后苏木精-伊红(HE)染色观察胰腺组织病理学改变。采用酶联免疫吸附试验(ELISA)分析血清白细胞介素(IL)-1β和IL-18水平,采用自动生化仪检测血清淀粉酶水平;采用蛋白质印迹法(Western blot)分析半胱氨酰天冬氨酸特异性蛋白酶-1前体(pro-Caspase-1)和半胱氨酰天冬氨酸特异性蛋白酶-1(Caspase-1)表达水平。计量数据比较采用方差分析,进一步两两比较采用LSD-t检验。结果治疗组病理学评分[(6.81±2.01)分]低于模型组[(10.45±3.19)分],差异有统计学意义(t=3.819,P<0.05)。治疗组血清淀粉酶水平[(2091.44±302.81)U/L]低于模型组[(4912.45±590.32)U/L],差异有统计学意义(t=4.819,P<0.05)。治疗组血清IL-1β和IL-18水平[(210.49±19.58)、(310.40±28.71)ng/L]低于模型组血清IL-1β和IL-18水平[(409.34±29.81)、(529.59±38.39)ng/L],差异有统计学意义(t=6.019、7.012,P<0.05)。治疗组pro-Caspase-1和Caspase-1表达水平(0.51±0.11、0.32±0.11),模型组pro-Caspase-1和Caspase-1表达水平(0.19±0.09、0.53±0.08),治疗组pro-Caspase-1的表达水平高于模型组,治疗组Caspase-1表达水平低于模型组,差异均有统计学意义(t=2.193、2.891,P<0.05)。结论NLRP3抑制剂CY-09可显著抑制NLRP3炎症小体活性,降低pro-Caspase-1激活,降低IL-1β和IL-18水平,进而对急性胰腺炎起到保护作用。     

白细胞介素-10对蛛网膜下腔出血所致脑血管痉挛的治疗作用及机制

目的 观察白细胞介素(IL)-10在蛛网膜下腔出血(SAH)后的脑血管痉挛(CVS)中的治疗作用及其作用机制.方法 日本大耳白兔(30只)随机分为假手术组(A)、SAH组(B)、SAH+IL-10组(C)、SAH+锌原卟啉(ZnPP)+ IL-10组(D)、SAH+ ZnPP组(E),经枕大池2次注血法建立兔SAH后CVS动物模型,术后C、D、E组分别经腹腔注射给予IL-10、ZnPP,术后第5天采用酶联免疫吸附试验(ELISA)法检测血清中肿瘤坏死因子-α(TNF-α)、IL-6的水平,取基底动脉血管检测血管直径并检测血红素氧合酶-1(HO-1)的表达.结果 SAH后血管痉挛模型造模成功,SAH各组基底动脉直径比A组明显缩小(P＜0.05),TNF-α与IL-6含量升高(P＜0.05),其中基底动脉直径在C、D组[(733.94±17.28)、(646.11±9.79)μm]较B、E组[(595.64±10.15)、(532.81±17.09) μm]增加,TNF-α和IL-6含量在C组[(26.27±1.64)、(58.15±1.38) ng/L]、D组[(43.45±1.77)、(77.17±1.09) ng/L]较B组[(53.56±1.27)、(115.93±1.47) ng/L]、E组[(60.56±1.79)、(136.45±1.73) ng/L]降低;A组脑基底动脉未检测到HO-1蛋白,C组HO-1含量(0.446±0.019)较B、D、E(0.314±0.014、0.251±0.018、0.160±0.011)组含量增加.结论 IL-10能够缓解SAH后所致CVS,可能是经HO-1蛋白发挥其治疗作用.     

骨髓间充质干细胞对大鼠慢性胰腺炎炎性因子的影响

目的 观察骨髓间充质干细胞(BMSCs)对大鼠慢性胰腺炎(CP)炎性因子的影响。方法 将80只SD大鼠随机分为空白组(20只,注射无菌生理盐水),模型组[20只,尾静脉注射二丁基二氯化物(DBTC)制作大鼠CP模型],假治疗组(20只,尾静脉注射DBTC制作大鼠CP模型后,输入和BMSCs等量的无菌生理盐水)和治疗组(20只,于CP模型制作成功后尾静脉注射体外培养的同种异体BMSCs)。80 d后采用酶联免疫吸附试验(ELISA)法检测各组大鼠胰腺中白细胞介素(IL)-1、IL-6、IL-8、IL-10、肿瘤坏死因子(TNF)-d、转化生长因子(TGF)-β水平。结果 治疗组中IL-1 (652.326±36.424) ng/L,IL-6(8.347±1.094) ng/L,IL-8( 352.487±69.340) ng/L,rGF-β(0.020±0.006) μg/L,均低于假治疗组与模型组(P＜0.05),IL-10(603.799±89.374) ng/L,TNF-α( 507.450±90.130)μg/L则高于假治疗组和模型组(P＜0.05)。模型组和假治疗组之间IL-1、IL-6、IL-8、IL-10、TNF-α、TGF-β的表达水平差异无统计学意义(P＞0.05)。结论 同种异体BMSCs的输入可以降低CP中促炎因子的水平,提高抗炎因子的浓度,有助于减轻CP的炎症反应,减缓甚至阻止CP的发展。     

α7 烟碱型乙酰胆碱受体在电针减轻肢体缺血再灌注兔肺损伤中的作用

目的:观察α7烟碱型乙酰胆碱受体(α7nAChR)在电针减轻肢体缺血再灌注诱发兔肺损伤中的作用。方法:40只健康雄性新西兰大白兔,采用随机数字表法分为假手术组、模型组、电针组和α-银环蛇毒素(α-BGT)组(n=10)。采用夹闭股动脉3 h、再灌注4 h的方法制备兔肢体缺血再灌注模型;电针组、α-BGT组于模型制备前1～4 d(30 min/次,1次/d)及模型制备过程中电针足三里穴和肺俞穴(电流l～2 mA,频率2/15 Hz,疏密波);α-BGT组于模型制备前30min腹腔注射α7nAChR拮抗剂α-BGT(1μg/kg)。再灌注4 h时采集颈动脉血样,随后处死兔取肺组织,观察病理学结果并行肺损伤评分,计算肺湿/干重(W/D)比值。采用ELISA法检测肺组织肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)含量,Western blot法检测α7nAChR蛋白表达水平。结果:模型组、电针组和α-BGT组再灌注4 h时肺组织W/D比值分别为6.89±1.07、4.56±0.75、8.68±1.49,均明显高于假手术组(2.83±0.43,P0.05);肺损伤评分分别为7.52±1.05、4.16±0.68、9.23±1.57,均明显高于假手术组(1.19±0.22,P0.05);TNF-α分别为(13.3±2.3)pg/mg、(11.0±1.6)pg/mg、(14.1±3.0)pg/mg,均明显高于假手术组[(3.2±0.3) pg/mg,P0.05];IL-1β分别为(9.2±2.0)pg/mg、(7.4±1.7)pg/mg、(10.5±1.9)pg/mg,均明显高于假手术组[(2.1±0.5) pg/mg,P0.05];IL-6分别为(14.2±2.3)pg/mg、(11.7±2.0)pg/mg、(14.8±1.8)pg/mg,均明显高于假手术组[(4.2±0.7)pg/mg, P0.05];α7nAChR表达水平分别为(0.55±0.09)、(0.87±0.14)、(0.33±0.08),均明显高于假手术组(0.23±0.04,P0.05)。与模型组比较,电针组再灌注4h时肺组织W/D比值、肺损伤评分、肺组织TNF-α、IL-1β、IL-6含量均显著降低(P0.05),电针组α7nAChR表达均显著上调(P0.05)。与电针组比较,α-BGT组再灌注4h时肺组织W/D比值、肺损伤评分、肺组织TNF-α、IL-1β、IL-6含量升高(P0.05),α7nAChR表达下调(P0.05)。结论:α7nAChR表达上调,可能参与了电针减轻肢体缺血再灌注诱发兔肺损伤的过程。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

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.