可注射性藻酸钙凝胶载体组织工程性软骨的实验研究

目的 对经体外培养的软骨细胞与藻酸钙凝胶载体复合形成的组织工程性软骨进行组织形态学观察。方法 取 2周龄新西兰白兔的膝关节软骨细胞,经体外培养两次传代后与藻酸钠溶液复合,使细胞密度为 5× 10 6/ml、 NaCl 0.135 mol/L、 K 2HPO 4 0.1 mol/L、藻酸钠的质量分数为 1％,然后注入葡萄糖酸钙使终浓度为 40 mmol/L。在实验组 (A、 B组 )兔的背部皮下注入复合藻酸钙载体的软骨细胞悬液,对照组 (C、 D组 )动物或注入无载体的软骨细胞悬液或注入无细胞的藻酸钙载体,分别于注射后第 2周、第 4周取材,进行 HE和甲苯胺蓝染色。结果 实验组,于注射复合软骨细胞的藻酸钙凝胶载体第 2周时, HE染色结果显示皮下注射点出现大量软骨细胞增殖,第 4周时有软骨组织形成;甲苯胺蓝染色见有软骨细胞和软骨基质形成。在注入无载体的软骨细胞悬液组 (C组 ),部分动物的皮下注射点有少量软骨组织形成,而在注入无细胞的藻酸钙载体组 (D组 )则未见软骨形成。结论 应用可注射性藻酸钙凝胶载体复合软骨细胞可在同种异体动物体内形成新生软骨组织。     

益气化瘀方减轻HIF-1α条件性基因敲除小鼠膝关节软骨退变的研究

目的:观察低氧诱导因子-1α(HIF-1α)条件性基因敲除(HIF-1αcKO)小鼠膝关节软骨退变情况,以及中药复方益气化瘀方对减缓HIF-1αcKO小鼠椎间盘软骨退变的作用。方法:①将杂交繁殖获得同窝的HIF-1α+/+小鼠和HIF-1α-/-小鼠,分为HIF-1α+/+小鼠4月龄组、HIF-1α-/-小鼠4月龄组,HIF-1α+/+小鼠6月龄组、HIF-1α-/-小鼠6月龄组,每组3只。在4、6月龄依次处死相应的小鼠,取膝关节软骨,分别进行Mankin评分、藏红固绿、HE及免疫组化相关指标染色及分析,研究软骨组织的改变情况。②将2月龄HIF-1α-/-小鼠随机分为生理盐水组和益气化瘀方组,以生理盐水组小鼠作为正常对照,每组6只,共12只。灌胃给药2个月后,取各组小鼠的膝关节,分别进行Mankin评分、HE染色和藏红固绿染色,ColⅡ、ColX、VEGF、MMP-13和Sox9免疫组化染色及分析。结果:①HIF-1α-/-小鼠4月龄组膝关节软骨组织出现破损和骨化,细胞分布不均匀,软骨细胞减少。HIF-1α-/-小鼠6月龄组膝关节软骨损伤更加严重。HIF-1α-/-小鼠4月龄组椎间盘软骨中Ⅱ型胶原(ColⅡ)和Sox9表达降低,X型胶原(ColX)、基质金属蛋白酶-13(MMP-13)、VEGF蛋白表达增加。HIF-1α-/-小鼠6月龄组ColⅡ蛋白与Sox9表达进一步降低,ColX、MMP13、VEGF蛋白表达进一步上升。②与生理盐水组比较,益气化瘀方干预后膝关节软骨部位的骨化和缺损减轻,软骨细胞分布较均匀,细胞总数增加。免疫组化染色显示,益气化瘀方组ColⅡ和Sox9蛋白的表达升高,ColX、VEGF、MMP-13蛋白表达减少。结论:HIF-1α基因敲除小鼠出现了膝关节软骨退变,并且这种退变随着小鼠增龄而加重;益气化瘀方可以减轻HIF-1α基因敲除小鼠的膝关节软骨退变。     

SIRT1基因敲除对骨关节炎小鼠VEGF/AKT信号通路的影响

目的通过研究沉默信息调节因子1(SIRT1)基因敲除对骨关节炎小鼠VEGF/AKT通路的作用,探讨骨关节炎关节软骨退变的可能机制。方法将小鼠分为两组:SIRT1~(+/+)小鼠骨关节炎模型组(A组,n=6);SIRT1~(-/-)小鼠骨关节炎模型组(B组,n=6)。荧光定量聚合酶链反应检测SIRT1基因表达情况;HE染色、番红O-固绿双染色观察膝关节软骨形态结构改变,Mankin评分评价膝关节关节软骨退变,免疫组化染色检测膝关节软骨细胞中SIRT1、VEGF和AKT蛋白水平。结果 B组SIRT1 m RNA表达量为2.24417±1.316569,明显低于A组(P0.01)。HE染色和番红O-固绿双染色结果显示,B组膝关节关节软骨退变明显,Mankin评分分值为9.8333±1.94079分,明显高于A组(P0.05),B组SIRT1、VEGF和AKT免疫组化染色积分分别为3.3333±1.96638、10.0000±2.44949和1.3333±1.21106,B组SIRT1蛋白表达与A组相比差异不显著(P0.05);B组VEGF蛋白表达明显高于A组(P0.05);B组AKT蛋白表达明显低于A组(P0.01)。结论 SIRT1基因敲除可能通过激活VEGF/AKT通路加重骨关节炎关节软骨的退变,因此SIRT1基因可能对骨关节炎起到保护作用。     

降钙素在体内体外实验中对兔关节炎关节软骨退变及软骨下骨骨代谢的影响

[目的]研究降钙素(calcitonin, CT)对骨性关节炎关节软骨退变和软骨下骨骨代谢的影响.[方法]30只3个月龄雌性日本大耳白兔随机分为三组,其中两组行右膝关节前交叉韧带切断术(anterior cruciate ligament transaction,ACLT),分为ACLT+CT组和ACLT+NS组,第3组为Sham组.ACLT+CT给予每日1次皮下注射降钙素5 IU/(kg·d),持续8周,ACLT+NS组给予同样剂量生理盐水.术后8周后处死所有动物.取股骨髁制成切片行MMP-13和Ⅱ型胶原免疫组化染色.取胫骨近端制成硬组织切片行骨形态计量学检测.体外实验中,取兔膝关节软骨,经消化、培养,将第3代软骨细胞分三组:向IL-1β组加入人重组IL-1β(10 ng/ml). IL-1β+CT组加入人重组IL-1β (10 ng/ml)2 d后,再向培养液中加入CT(50 ng/ml).正常组不加任何诱导剂和干扰剂培养.然后行MMP-13、Ⅱ型胶原免疫组化检测和Realtime RT-PCR法检测.[结果]Sham组和ACLT+CT组软骨下骨骨小梁相对体积和厚度等均显著高于ACLT+NS组.Sham组和ACLT+CT组的Ⅱ型胶原的光密度值均显著高于ACLT+NS组,而MMP-13的光密度值显著低于ACLT+NS组(P<0.05).正常组和IL-1β+CT组的Ⅱ型胶原光密度值均显著高于IL-1β组而MMP-13的光密度值都显著低于IL-1β组(P<0.05).在正常组和IL-1β+CT组中Ⅱ型胶原的mRNA含量均显著高于IL-1β组而MMP-13的mRNA含量均显著低于IL-1β组(P<0.05).[结论]降钙素5 IU/(kg·d)皮下注射能够增加ACLT兔膝关节软骨Ⅱ型胶原的分泌和抑制MMP-13的表达,并可能通过调节软骨下骨的骨代谢和微结构来保护关节软骨; CT(50 ng/ml)能增加体外培养的含有IL-1β(10 ng/ml)的软骨细胞中Ⅱ型胶原的含量和抑制MMP-13分泌.     

增强绿色荧光蛋白标记比较腺病毒、腺相关病毒体外转染兔软骨细胞的效果

目的 通过增强绿色荧光蛋白(eGFP)标记,比较腺病毒(Ad)、腺相关病毒(AAV)对体外培养软骨细胞的转染效果.方法 体外培养正常3月龄新西兰兔关节软骨细胞,以rAd5-eGFP、rAAV2-eGFP分别转染原代关节软骨细胞,计算最佳传染复数.之后以最佳传染复数的病毒重组体转染软骨细胞,分别应用流式细胞仪检测绘制转染率的时间一反应曲线,倒置荧光显微镜下观察转染后细胞的大体形态、绿色荧光的表达情况并应用荧光定量PCR检测转染前后软骨细胞Ⅱ型胶原mRNA表达水平的变化.结果 rAd5-eGFP、rAAV2-eGFP的最佳传染复数分别为1×103 vp/cell和1×105 vg/cell.分别应用最佳传染复数体外转染原代培养的软骨细胞后,rAd5-eGFP在转染后1～2 d荧光表达即可达到高峰,但之后迅速衰减,在转染后第28天基本检测不到荧光表达.rAAV2-eGFP在转染第7天荧光表达达高峰,随之缓慢衰减,在转染后第56天仍可检测到绿色荧光表达.荧光定量PCR检测显示,rAd5-eGFP在转染软骨细胞后,软骨细胞合成Ⅱ型胶原mRNA的水平明显下降,而rAAV2-eGFP则影响不显著.结论 Ad转染体外培养的关节软骨细胞后,目的基因的表达迅速,但维持时间短,对软骨细胞表型的影响较明显;AAV转染软骨细胞后,目的基因的表达缓慢,但维持时间长,且对软骨细胞表型的影响较小.AAV更适于作为软骨细胞的体外转染载体.     

白藜芦醇激活PI3K/Akt信号通路对软骨细胞细胞外基质合成的影响

[目的]通过白藜芦醇刺激体外培养的小鼠膝关节软骨细胞,探讨白藜芦醇通过PI3K/Akt信号通路对软骨细胞细胞外基质合成的影响。[方法]体外分离培养小鼠膝关节软骨细胞,采用HE染色、甲苯胺蓝染色和Ⅱ型胶原免疫荧光染色观察鉴定软骨细胞。根据作用药物的不同分为3组:空白对照组、白藜芦醇组(100μmol/L白藜芦醇)和LY294002组(100μmol/L白藜芦醇+25μmol/L LY294002)。采用RT-PCR检测软骨细胞中Akt1,Aggrecan、Collagen II的m RNA表达水平。[结果]荧光显微镜下可见软骨细胞胞核呈蓝色荧光,胞质呈红色荧光。显示Ⅱ型胶原染色阳性细胞数占90%以上,证实所培养细胞为软骨细胞。RT-PCR检测结果显示白藜芦醇组Akt1、Aggrecan、Collagen II m RNA表达量较空白组明显升高(P<0.05)。LY294002组Akt1、Aggrecan、Collagen II m RNA表达量较白藜芦醇组下降,但仍高于空白组(P<0.05)。[结论]白藜芦醇可以通过激活PI3K/Akt信号通路,增加软骨细胞细胞外基质合成,起到保护关节软骨的作用。     

应用碱性成纤维细胞生长因子体外扩增猪耳软骨细胞老化的规律

目的探讨碱性成纤维细胞生长因子(bFGF)体外扩增软骨细胞的老化规律。方法细胞取自猪耳弹性软骨,实验分两组:培养液含10μg/L b-FCF组(简称bFGF组),培养液无bF- GF组(简称对照组),分别收集两组多代细胞,按5×107个/ml浓度与30%Pluronic F-127/Ham’s F-12混合,按每一样本0.5 ml注射到猪自体皮下,8周后取材,从大体观察、称重及组织学染色,对再生的软骨组织进行评价。结果bFGF组和对照组从第3代开始均未能形成软骨组织,bFGF组第2代软骨细胞和原代比较,在两周内扩增70倍,是对照组的12.7倍,且体内能形成很好的软骨。结论应用bFGF体外扩增的软骨细胞在第3代开始老化,失去成软骨能力,种子细胞应取第2代,可兼顾适量细胞数与具备成软骨能力。     

负载miRNA-27b的BMSCs来源的外泌体治疗实验性骨关节炎

[目的]探讨负载miRNA-27b的间充质干细胞来源的外泌体(MSC-27b-Exos)对炎症环境下的软骨细胞的保护作用。[方法]体外利用10 ng/ml白介素-1β(IL-1β)建立软骨细胞炎症环境模型,采用超速离心法收集外泌体,分别以80μg/ml的MSC-27b-Exos,普通外泌体MSC-Exos、inhibitor沉默的MSC-27boff-Exos作用炎症环境下的软骨细胞,并设PBS处理为对照组,检测各处理组软骨细胞凋亡水平,Western blot检测软骨细胞中MMP-13,及凋亡蛋白Caspase的表达水平。体内实验:20只雄性SD大鼠随机分为4组,建立创伤性骨关节炎(post-traumatic osteoarthritis, PTOA)模型,分别注射等量的MSC-miR27b-Exos、MSC-miR27b~(off)-Exos,并设立单纯PBS组和假手术组,6周后取材,观察关节软骨形态;ELISA检测关节液中IL-1β、TNF-α的含量;免疫组化对比各组Ⅱ型胶原表达。[结果]体外实验中,MSC-27b-Exos组的软骨细胞增殖能力较MSC-miR27b~(off)-Exos组增强,较空白组明显旺盛(P0.05),在炎症环境下软骨细胞凋亡明显减弱(P0.05),MSC-27b-Exos组软骨细胞中cleave-Caspase-9水平降低(P0.05),cleave-Caspase-3水平降低(P0.05),MMP-13相对含量减少。SD大鼠体内实验显示, MSC-27bExos组对软骨缺损修复效果优于空白组和MSC-miR27b~(off)-Exos组。MSC-27b-Exos组关节液中IL-1β、TNF-α的含量低于空白组,明显低于MSC-27b~(off)-Exos组。[结论]在实验型SD大鼠PTOA模型中,利用MSC-27b-Exos关节腔内注射具有明显抗炎的作用和减缓关节软骨退行性变。     

创伤后关节软骨细胞凋亡及其预防的实验研究

目的探讨关节软骨创伤后软骨细胞凋亡情况及其预防方法。方法32只新西兰大白兔,4只行膝关节囊切开,不损伤软骨(正常组),另28只双侧膝关节钻孔造成软骨急性损伤,一侧关节腔在术毕和术后每周1次注射1％透明质酸钠1 mL(治疗组),另一侧不做处理作为损伤对照(损伤组);利用TUNEL、流式细胞仪两种方法检测软骨受损区软骨细胞凋亡情况。结果损伤后软骨细胞出现坏死和凋亡,至第4天软骨细胞凋亡率最大,凋亡细胞全层分布;透明质酸钠治疗组软骨细胞凋亡较损伤组明显减少,差异有极显著性意义(P<0．01)。结论创伤后关节软骨细胞发生凋亡会导致创伤后骨关节炎的发生。早期关节腔内注射透明质酸钠能有效抑制软骨细胞凋亡,可能对预防和降低创伤后骨关节炎的发生有重要意义。     

医用臭氧对膝骨关节炎兔软骨基质金属蛋白酶-1的影响

目的 探讨医用臭氧对膝骨关节炎兔软骨基质金属蛋白酶-1(MMP-1)的影响.方法 新西兰大白兔30只,体重2.2～2.8 kg,雌雄不拘,并以左膝关节作为对比,随机分为3组,每组10只,建立右膝骨关节炎(OA)模型,分别于造模成功后第3天和第5天向右膝关节腔内注入空气(A组)、40μg/L(B组)和80 μg/L(C组)医用臭氧3 ml.造模成功后第7天处死动物,取两膝关节,光镜下观察关节软骨一般形态,甲苯胺蓝染色行Mankin评分;免疫组化法检测软骨基质金属蛋白酶-1(MMP-1)的表达水平;分别于造模成功时和处死前即刻测定兔两膝关节活动度.结果 与左膝关节比较,各组造模成功时右膝关节活动度降低,软骨组织Mankin评分、软骨细胞MMP-1表达升高(P＜0.05);B组和C组处死前即刻右膝关节活动度较造模成功时升高(P＜0.05).与A组比较,B组软骨组织Mankin评分、软骨细胞MMp-1表达降低(P＜0.05);与B组比较,C组上述指标升高(P＜0.05).A组和C组软骨明显退变,程度重于B组.结论 关节腔内注射40 μg/L医用臭氧3ml治疗兔膝骨关节炎的机制可能与下调软骨MMP-1有关.     

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.     

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.     

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.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.