糖尿病合并去势大鼠骨微结构退化的研究

目的探讨糖尿病合并去势大鼠骨微结构的改变。方法 6月龄雌性大鼠40只,随机分为对照组、假手术组、去势组、糖尿病组和糖尿病合并去势组。6 w和15 w后应用Micro-CT测定股骨检测骨密度和骨微结构;利用Van Gieson胶原纤维染色法观察胶原纤维沉积变化;HE染色分析大鼠股骨头骨小梁厚度(Tb.Th)和骨小梁间距(Tb.Sp)变化。结果与对照组相比,去势6 w和15 w组骨β-胶原降解产物水平和Tb.Sp明显升高,骨密度值和Tb.Th明显下降。去势15 w组骨胶原纤维明显下降,差异有统计学意义(P0.05)。糖尿病组15 w松质骨β-胶原降解产物水平、胶原纤维和Tb.SP明显升高,骨密度值、胶原纤维和Tb.Th明显下降,差异有统计学意义(P0.05)。糖尿病合并去势组6 w和15 w组松质骨β-胶原降解产物水平、胶原纤维和Tb.Sp明显升高,骨密度值和Tb.Th明显下降,差异有统计学意义(P0.05)。结论糖尿病合并去势早期是以去势为主导致的骨质疏松,后期则由糖尿病缓慢的骨分解加持,骨质疏松继续加重。     

骨质疏松绵羊模型松质骨及皮质骨的微观结构及力学性能变化的研究

目的观察去势手术对绵羊皮质骨和松质骨的骨密度、骨小梁结构及力学性能的影响。方法20只雌性成年绵羊（4±1.5）随机分为去势4个月组（OVX-4months）（4只）、去势12个月组（OVX-12months）（8只）和假手术（Sham）组（8只）。OVX组行双侧卵巢切除术,假手术组仅显露双侧卵巢,术中测定腰椎骨密度。分别与术后4、12个月处死动物,测定股骨颈、股骨干及股骨髁的骨密度,并行MicroCT分析及生物力学测试。结果去势12个月后（OVX-12months）组腰椎、股骨颈及股骨髁的骨密度较对照组显著降低,而皮质骨骨密度无明显降低。其松质骨的相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）较对照组显著降低,表面积体积比（BS/BV）、骨小梁间隙（Tb.Sp）则较对照显著增高。生物力学测试表明,去势12个月后,腰椎松质骨的最大压缩应力分别较Sham组和OVX-12months组下降82.5%和85.9%,力学强度显著下降,而皮质骨的力学强度无显著变化。结论去势12个月后,绵羊腰椎、股骨部的松质骨BMD及骨小梁空间结构参数明显降低,力学强度也显著下降,可以作为骨质疏松的大动物模型。而皮质骨的骨密度和力学强度下降不明显,需要更长的去势时间。     

化瘀补肾方对卵巢切除小鼠骨折愈合的作用

目的观察化瘀补肾方对卵巢切除小鼠骨折愈合的作用。方法 3月龄雌性C57BL/6小鼠48只分为假手术组、模型组和化瘀补肾方组各16只。模型组和化瘀补肾方组小鼠采用双侧卵巢切除术(OVX)建立骨质疏松症模型。术后12周,各组小鼠建立左侧胫骨中段骨折模型。术后给予化瘀补肾方组小鼠化瘀补肾方灌胃,给予假手术组与模型组小鼠等体积生理盐水灌胃,至骨折术后4周取材。检测各组小鼠血清雌二醇水平,采用Micro-CT检测小鼠第4腰椎及左侧胫骨的骨密度,检测左侧胫骨最大应力,对左侧胫骨石蜡切片进行阿尔辛蓝/橙黄G染色,观察骨组织形态学变化。结果 OVX后4周开始,模型组小鼠体重明显升高,并持续高于假手术组(P0.01)。骨折术后4周,模型组小鼠血清雌二醇和第四腰椎骨密度(BMD)明显低于假手术组(P0.01),化瘀补肾方组小鼠血清雌二醇水平和第四腰椎BMD高于模型组(P0.01)。Micro-CT三维重建显示,模型组左侧胫骨仍有明显的骨折线,骨痂生长不明显,化瘀补肾方组骨折线模糊,骨痂形成明显。与假手术组相比,模型组小鼠的BV/TV(P0.01)、Tb.Th(P0.05)和Tb.N(P0.01)均明显降低,Tb.Sp明显升高,化瘀补肾方组小鼠的BV/TV(P0.05)、Tb.Th(P0.05)相较于模型组则显著升高,但Tb.N、Tb.Sp差异无统计学意义。与假手术组比较,模型组小鼠胫骨的最大应力在骨折术后28 d时显著低于假手术组(P0.01),化瘀补肾方组小鼠胫骨的最大应力显著高于模型组(P0.01)。阿尔辛蓝/橙黄G染色显示,假手术组和化瘀补肾方组骨痂组织处于塑形期,可见明显骨小梁结构,而模型组骨痂组织内见大量脂肪组织,骨小梁稀疏。结论化瘀补肾方能有效促进去卵巢小鼠的骨折愈合,改善愈合骨组织的生物力学性能。     

耐力运动对骨质疏松小鼠骨量、骨形态学及Linc-ROR表达的影响

目的研究长链非编码RNA-linc-ROR在运动预防卵巢切除小鼠骨量丢失、改善骨形态学破坏中的作用。方法 24只3月龄雌性C57BL小鼠随机分为假手术组(Sham)、卵巢切除组(Ovx)、卵巢切运动组(Ex)。Ex小鼠接受8周下坡跑训练,8周后所有小鼠处死,收集血液、骨骼标本检测血清激素(ELISA)、骨密度(bone mineral density,BMD)、骨形态学指标(micro-CT)及相关基因(PCR)与蛋白(Western blot)表达。采用STATA 15软件统计组间差异。结果 Ovx小鼠出现BMD下降,骨体积(bone volume/total volume,BV/TV)、骨小梁厚度(trabecular thickness,Tb.Th)、骨小梁数量(trabecular number,Tb.N)减小,骨小梁间距(trabecular separation,Tb.Sp)增加;运动增加Ovx小鼠BMD、BV/TV、Tb.Th和Tb.N,减少Tb.Sp。相比Ovx组,Ex小鼠骨组织中碱性磷酸酶阳性(alkaline phosphatase positive,ALP~+)成骨细胞数量增多。Ovx小鼠血清雌二醇(estradiol,E_2)、骨保护素(osteoprotegerin,OPG)下降,核因子κB受体配体(receptor activator of NF-κB ligand,RANKL)升高,运动明显增加血清E_2、OPG水平,降低RANKL浓度。Ovx小鼠骨组织Linc-ROR及Wnt3、β-catenin mRNA和蛋白表达下降,运动上调这些基因、蛋白的表达。结论耐力运动可预防骨质疏松小鼠骨量丢失、改善骨微观结构,Linc-ROR/Wnt/β-catenin信号通路可能参与这一过程。     

卵巢切除对大鼠骨骼结构与力学特征的早期影响

[目的]评估雌性大鼠卵巢切除术后早期椎骨和股骨的骨结构和抗压应力变化特点。[方法] 50只12周龄的雌性SD大鼠随机分为两组,每组25只。分别行双侧卵巢切除和假手术处理。于术后1、4、8、12、16周时每组各随机选取5只大鼠,测量体重,行Micro-CT骨计量、压应力模量检测和组织形态观察。[结果]随时间推移,两组动物体重均显著增加(P0.05)。术后4～16周,去势组的体重均显著大于假手术组(P0.05)。Micro-CT骨计量检测方面,随时间推移,去势组椎骨和股骨标本的BV/TV、Conn. D和Tb.N显著下降,而Tb.Sp显著增加(P0.05),但是Tb.Th无显著改变(P0.05);相比之下,假手术组不同时间点间的BV/TV、Conn. D、Tb.N、Tb.Th和Tb.Sp均无显著变化(P0.05)。术后4～16周,去势组BV/TV显著低于假手术组(P0.05)。力学测试方面,术后4～16周,去势组标本的弹性模量均小于假手术组,但相应时间点,两组间差异均无统计学意义(P0.05)。组织学方面,随时间推移,与假手术组相比,去势组骨小梁数量减少,间隙增宽,骨小梁连续性变差。[结论]相比力学测试,Micro-CT骨计量检测能更早期反映雌激素缺失造成的骨变化。     

小鼠非酒精性脂肪肝纤维化对骨微结构的影响及姜黄素治疗作用

目的探讨非酒精性脂肪肝(NAFLD)小鼠模型肝纤维化对骨微结构影响及姜黄素的治疗作用。方法 6周龄雌性野生型C57BL/6小鼠30只,随机分为野生小鼠对照组(WT组,n=10),高脂饮食组(HFD组,n=10)和姜黄素治疗组(HFD+Cur组n=10)。对照组给予普通饲料饲养,高脂饮食组给予高脂饮食饲养,姜黄素治疗组除了给予高脂饮食外,在24周时给予姜黄素治疗。各组小鼠于32周末处死,检测小鼠血清生化指标,以及小鼠血清中TNF-α,IL-6,IGF-1和IGFBP-1的水平,肝组织HE染色后进行光镜病理学检测,micro-CT分析骨微结构及骨密度。结果与WT组相比,HFD组血清中AST、IL-6、TNF-α明显升高(P0.05),而体重、TC、ALT、IGF-1、IGFBP-1变化更加明显(P0.01);小鼠肝组织纤维化增生明显,同时胫骨近端参数BV/TV、Tb.Th、Tb.N、Tb.Sp、Conn.D/mm~3、C.Th、v BMD、t BMD及骨干形态与WT组相比差异具有统计学意义(P0.05、P0.01);通过姜黄素治疗后除IGF-1水平明显升高(P0.05),小鼠体重以及血清中其余各指标水平明显下降(P0.05),更接近于WT组(P0.05);肝脏病理学未见明显坏死灶及纤维化,小鼠骨微结构参数及骨干形态较HFD组明显好转(P0.05、P0.01),部分参数接近WT组(P0.05)。结论小鼠非酒精性脂肪肝纤维化期可出现明显骨量丢失,血清中TNF-α、IL-6、IGF-1和IGFBP-1变化在其发病机制中起到重要的作用,其中IGF-1和IGFBP-1作用尤为重要,而姜黄素通过调节这些细胞因子可减轻脂质聚集,增加骨小梁、骨皮质及骨密度。     

血清中骨质疏松相关蛋白分子标志物的筛选研究

目的：通过蛋白芯片筛选血清中反映早期绝经后骨质疏松症发生、发展的标志性分子。方法3月龄雌性SD大鼠20只，随机分为卵巢切除（ovariectomized, OVX）组和假手术（sham operation, Sham）组，每组10只，分别进行卵巢去势手术和假手术处理。术后2、4、6、8周对两组大鼠进行活体显微CT扫描，测量股骨远端骨密度及相关松质骨形态计量学动态参数；同时经内眦静脉取血，利用蛋白芯片检测血清中不同蛋白因子的含量。结果显微CT检测结果显示OVX组大鼠骨密度（BMD）、相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）从第4周开始下降，骨小梁分离度（Tb.Sp）开始上升， Sham组未见明显变化；到第8周各指标在OVX组与Sham组之间差异有统计学意义（P＜0.05）。蛋白芯片检测结果显示OVX组中干扰素?γ（IFN?γ）、β神经生长因子（b?NGF）分别从术后4周和6周后开始升高，同Sham组比较均至第8周具有明显差异（P＜0.05）。结论 IFN?γ和b?NGF水平在绝经后骨质疏松早期开始增高，可考虑作为诊断早期绝经后骨质疏松症发生的新型蛋白分子。     

异补骨脂素对去卵巢骨质疏松小鼠骨髓间充质干细胞作用机制研究

目的探讨异补骨脂素对去卵巢骨质疏松小鼠骨髓间充质干细胞(bone mesenehymal stem cells,BMSCs)作用机制。方法18只C57/BL6雌鼠随机平均分为假手术组(Sham)、去卵巢组(OVX)和去卵巢加异补骨脂素组(OVX+ISO),各组6只。OVX组和OVX+ISO组分离背部近髂脊处肌肉,取出双侧卵巢,结扎上部输卵管,剪去双侧输卵管。Sham组相同入路后剪去包裹卵巢周围的部分脂肪组织。OVX+ISO组在去卵巢前5天开始灌胃异补骨脂素,灌胃剂量为20 mg/(kg·d),灌胃持续时间2个月,Sham组以等剂量生理盐水灌胃。造模后12周处死小鼠,取股骨下段评价骨髓腔中脂肪细胞量,行micro-CT扫描评价股骨下段骨量改变及RUNX2、PPAR-γ免疫荧光检测。结果异补骨脂素能明显减少由于去卵巢引起的股骨下段脂肪细胞增多;与此同时,异补骨脂素治疗能明显改善由于去卵巢引起的股骨下段骨量丢失,即OVX+ISO组骨小梁厚度(Tb.Th)、骨体积/总体积(BV/TV)、骨小梁数量(Tb.N)大于OVX组,差异具有统计学意义(P0.05);而OVX+ISO组骨小梁体积(Tb.Sp)小于OVX组,差异具有统计学意义(P0.05)。对去卵巢C57/BL6小鼠股骨下段进行RUNX2和PPAR-γ免疫荧光提示,异补骨脂素治疗能增加股骨下段由于去卵巢引起的RUNX2表达降低,同时能抑制PPAR-γ表达增加,即OVX+ISO组股骨下段RUNX2、PPAR-γ免疫荧光表达强度高于OVX组,差异具有统计学意义(P0.05)。结论异补骨质素对去卵巢小鼠BMSCs的作用机制为治疗骨质疏松提供了新的临床治疗手段。     

PM2.5对去势后雌性SD大鼠骨微结构micro-CT的影响

目的探讨不同浓度的PM_(2.5)暴露对去势SD雌性大鼠骨微结构的影响。方法用不同浓度(35、70、150μg/m3)的PM_(2.5)对SD大鼠进行气道滴注,随机分为低剂量组、中剂量组和高剂量组,滴注后5个月末行去势手术;滴注后9个月末取股骨、胫骨、腰椎,运用显微计算机断层扫描术(micro-CT)分别检测三者骨微结构。结果与对照组相比,PM_(2.5)暴露组胫骨、股骨、腰椎的骨小梁骨密度(Tb.BMD)减小、骨体积分数(BV/TV)减小、结构模型指数(SMI)增大、骨小梁厚度(Tb.Th)减小、骨小梁数量(Tb.N)减少、骨小梁分离度(Tb.Sp)增加; PM_(2.5)暴露组中,胫骨骨小梁的BV/TV、Tb.Th、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05),股骨骨小梁的Tb.BMD、BV/TV、SMI、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05),腰椎骨小梁的SMI、Tb.Th、Tb.N、Tb.Sp指标改变与对照组比较差异有统计学意义(P0.05)。从micro-CT三维重建图结果看,与对照组比较,PM_(2.5)暴露组胫骨骨髓腔内明显空虚,骨小梁缺如;股骨Ward三角区骨小梁数量稀疏、间隙变大;腰椎骨小梁结构的完整性被破坏,杆状结构增多。结论表明PM_(2.5)暴露可使去势后雌性SD大鼠胫骨、股骨、腰椎骨小梁结构遭到破坏,数量减少,由片状结构转为杆状结构,由此可见PM_(2.5)暴露可加重绝经后骨量丢失。     

朝藿定C联合骨髓间充质干细胞移植对糖皮质激素性骨质疏松小鼠骨密度和骨代谢的影响

目的 探讨朝藿定C联合骨髓间充质干细胞移植对糖皮质激素性骨质疏松小鼠骨密度和骨代谢的影响。方法 75只雄性C57BL/6小鼠分为空白对照组、模型组、朝藿定C组、干细胞移植组、联合组，每组各15只。空白对照组以0.1 mL生理盐水肌肉注射，其余4组以0.1mL地塞米松肌肉注射，2次/周，连续干预8周，以骨密度值确定造模成功。造模成功后7 d分别进行骨髓间充质干细胞移植和朝藿定C灌胃治疗，连续8周。测定骨密度和骨结构参数、血清骨代谢指标水平以及AKT蛋白磷酸化（p-AKT）水平。结果 与空白对照组比较，模型组体质量、骨矿物质含量（BMC）、骨矿物质密度（BMD）、组织矿物质含量（TMC）、组织矿物质密度（TMD）、骨体积分数（BV/TV）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）以及骨源性碱性磷酸酶（BALP）、Ⅰ型前胶原羧基端前肽（PINP）、AKT蛋白磷酸化水平显著降低，骨小梁分离度（Tb.Sp）显著增加，血清骨钙素（OCN）和抗酒石酸酸性磷酸酶（Trap）水平显著升高（P＜0.05）。与模型组比较，朝藿定C组、干细胞移植组和联合组小鼠体质量、BMC、BMD、TMC、TMD、BV/TV、Tb.N、Tb.Th显著增加，BALP、PINP、AKT蛋白磷酸化水平显著升高，Tb.Sp、血清OCN和Trap水平显著降低，且联合组上述指标改善优于其余2组（P＜0.05）。结论 朝藿定C联合骨髓间充质干细胞移植可促进糖皮质激素性骨质疏松小鼠骨形成，增加骨密度，改善骨微结构，其机制可能与提高骨代谢水平和活化PI3K/AKT通路有关。     

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.     

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.     

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.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

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.     

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery

Background: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i. e. in patients subjected to arthroscopic knee joint surgery.
Method: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group.
Results: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5–Th7, was reached within 30 min with a median duration of 3.6–3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i. v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33).
Conclusion: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.     

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.