补肾固本方对大鼠骨质疏松模型中PI3K/AKT/mTOR信号通路表达的调控研究

目的观察补肾固本方对去卵巢骨质疏松(osteoporosis,OP)大鼠骨组织中PI3K/AKT/mTOR信号通路的影响,探讨补肾固本方干预OP的作用机制。方法将100只SD大鼠随机分为5组:正常组(C组)、模型组(M组)、补肾固本方组(B组)、补肾固本方+PI3k受体特异性阻断剂LY294002组(B+L组)、PI3k受体特异性阻断剂LY294002组(L组),除正常组外,其余4组建立去卵巢大鼠OP模型。药物连续干预12周后,采用ELISA方法检测血清中E2、BGP、ALP水平,实时荧光定量聚合酶链式反应(Real-time PCR)检测各组股骨组织中LC3、Beclin1、caspase-9 mRNA的表达情况,蛋白质印迹法(Western blot)检测各组股骨组织中PI3K、AKT、mTOR蛋白的表达。结果补肾固本方可显著增高OP大鼠血清E2水平,降低BGP、ALP水平,显著上调LC3、Beclin1表达水平,降低caspase-9、PI3K、p-AKT、mTOR的表达;而上述变化能够被PI3k受体特异性阻断剂LY294002所阻断,且其差异具有统计学意义(P0.05)。结论补肾固本方减少去卵巢后大鼠OP的发生,其机制可能与抑制PI3K/AKT/mTOR信号通路及其下游基因蛋白表达有关。     

DESI2基因干扰联合PI3K抑制剂对人胰腺癌细胞ASPC-1的影响

目的 研究人凋亡相关新基因DESI2基因和PI3K抑制剂对人胰腺癌细胞ASPC-1的影响。方法 构建DESI2慢病毒干扰载体,并将细胞分为四组：（1）溶剂对照组;（2）PI3K抑制剂组;（3）DESI2干 扰+PI3K抑制剂组;（4）DESI2空载+PI3K抑制剂组。采用MTT检测细胞活性,流式检测细胞周期和调亡, Transwell检测细胞侵袭情况,qRT-PCR检测细胞DESI2、Caspase3、AKT、PI3K和mTOR mRNA的表达, Western blotting检测细胞DESI2、Caspase3、AKT、p-AKT、PI3K、p-PI3K、mTOR和p-mTOR蛋白表达情 况。结果 与溶剂对照组相比,PI3K抑制剂组和DESI2空载+PI3K抑制剂组细胞活性明显下降,G1期比 例升高,S期和G2期比例降低,凋亡明显升高,细胞侵袭能力明显下降,DESI2和Caspase3的mRNA和蛋 白水平表达明显升高,AKT、PI3K和mTOR及其磷酸化的蛋白表达量明显下降。与PI3K抑制剂组相比, DESI2干扰+PI3K抑制剂组细胞活性明显升高,G1期比例降低,S期比例升高,凋亡明显下降,细胞侵袭能 力明显升高,DESI2和Caspase3 mRNA和蛋白水平表达明显下降,AKT、PI3K和mTOR及其磷酸化的蛋白 表达量明显升高,研究数据组间比较均达到统计学显著水平（P<0.05）。 结论 PI3K抑制剂通过阻断PI3K/ AKT/mTOR信号通路,可以抑制人胰腺癌细胞ASPC-1的增殖及侵袭,促进细胞调亡;PI3K/AKT/mTOR信 号通路的功能状态能反馈调节上游DESI2基因的表达。     

阻断PI3K/AKT/mTOR通路增强顺铂诱导的人皮肤黑素瘤细胞株A375凋亡的机制研究

目的:本实验探讨抑制PI3K/AKT/mTOR通路对顺铂诱导人皮肤黑素瘤细胞株A375细胞凋亡作用及其机制。方法:用顺铂处理人皮肤黑素瘤细胞株A375细胞后Western blot检测细胞凋亡、PI3K/AKT/mTOR通路的活化情况以及细胞增殖-毒性检测试剂盒(Cell Counting Kit-8,CCK-8)。用PI3K的抑制剂LY294002(LY)和mTOR的抑制剂雷帕霉素(Rapamycin,Rap)分别预处理以研究其对顺铂处理后人皮肤黑素瘤细胞株A375细胞凋亡的协同作用。为进一步探索阻断PI3K/AKT/mTOR通路对顺铂处理后人皮肤黑素瘤细胞株A375细胞凋亡的协同作用机制,采用Western blot检测阻断PI3K/AKT/mTOR后联用顺铂处理人皮肤黑素瘤细胞株A375细胞中Bcl-2、Bcl-xl蛋白表达。结果:顺铂处理后的A375黑素瘤细胞中PARP的活化剪切体表达量水平呈浓度和时间依赖性增加,细胞活力呈浓度和时间依赖性降低(P0.05)。顺铂处理A375黑素瘤细胞后PI3K/AKT/mTOR通路的活化。阻断PI3K/AKT/mTOR通路再用顺铂联合处理A375黑素瘤细胞后PARP的活化剪切体表达量明显上调以及细胞活力明显降低(P0.05)。阻断PI3K/AKT/mTOR通路后再用顺铂联合处理A375黑素瘤细胞发现Bcl-2蛋白和Bcl-xl表达水平下调。结论:阻断PI3K/AKT/mTOR通路对顺铂诱导的细胞凋亡具有协同作用,该协同作用可能与Bcl-2和Bcl-xl蛋白下调有关。     

PI3K/AKT通路和S1PR2在急性梗阻性胆管炎诱导大鼠全身炎症反应中的作用

目的研究急性梗阻性胆管炎(AOC)大鼠模型中外周血单个核细胞(PBMCs)中磷脂酰肌醇-3-羟激酶(PI3K)/AKT通路和鞘氨醇-1-磷酸受体2(S1PR2)的激活情况以及其对大鼠全身炎症反应的影响。方法①体外实验:分离和培养清洁级大鼠PBMCs,然后将其分为磷酸盐缓冲溶液对照组、单独PI3K抑制剂LY294002处理组、脂多糖处理组和脂多糖+LY294002处理组4组,收集各组细胞的上清液和总蛋白,检测细胞上清液中炎性因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平以及细胞中PI3K、AKT磷酸化水平和S1PR2蛋白的变化。②体内实验:60只清洁级SD大鼠被随机分为假手术组、单独PI3K抑制剂LY294002处理组、AOC模型组及AOC模型+LY294002处理组4组,记录大鼠存活情况,检测大鼠血清中肝功能丙氨酸转氨酶(ALT)、门冬氨酸氨基转移酶(AST)和总胆红素(TBIL)水平及血清中TNF-α和IL-6的水平以及大鼠PBMCs中PI3K、AKT磷酸化水平和S1PR2蛋白的变化。结果①体外实验结果:脂多糖+LY294002处理组细胞上清液中TNF-α和IL-6水平均明显低于脂多糖处理组(P0.050),PI3K、AKT磷酸化水平和S1PR2的蛋白水平亦明显低于脂多糖处理组(P0.050)。②体内实验结果:AOC模型+LY294002处理组大鼠的生存率高于AOC模型组,血清中肝功能ALT、AST、TBIL和炎性因子TNF-α和IL-6水平均明显低于AOC模型组(P0.050),PI3K和AKT磷酸化水平及S1PR2蛋白表达水平也明显低于AOC模型组(P0.050)。结论抑制AOC模型大鼠中PBMCs中PI3K/AKT通路的活化,可降低S1PR2的表达,且能抑制AOC诱导的大鼠全身炎症反应。     

糖尿病性勃起功能障碍大鼠阴茎海绵体组织中神经生长因子的表达及其治疗作用的研究

目的:本研究通过检测糖尿病性勃起功能障碍(ED)大鼠阴茎组织中神经生长因子(NGF)表达,并使用hNGF进行治疗,以探讨糖尿病性ED发病机制及NGF治疗作用的机制。方法:成年雄性SD大鼠60只,随机取50只大鼠用于制作糖尿病模型,饲养8周后,取正常组和糖尿病组大鼠阴茎海绵体组织,采用RT-PCR和W estern印迹法检测NGF的mRNA及蛋白水平。从造模成功的糖尿病大鼠中筛选出有ED大鼠,把所有大鼠分为5组:正常组、糖尿病性ED组、糖尿病性ED单用NGF组(NGF组)、糖尿病性ED单用胰岛素组(R I组)、糖尿病性ED联合应用NGF和胰岛素组(NGF+R I组,胰岛素通过颈部皮下注射给药,NGF通过腹腔内注射给药),8周后测海绵体内压(ICP),并取所有大鼠阴茎海绵体组织用免疫组化法观察nNOS神经纤维的变化。结果:与正常组相比,糖尿病性ED组大鼠阴茎海绵体组织中NGF的mRNA表达增加,蛋白含量增加。与糖尿病性ED组相比,NGF组、R I组、NGF+R I组ICP水平显著升高(P<0.05);NGF组、R I组、NGF+R I组阴茎组织中nNOS神经纤维水平显著升高(P<0.05)。结论:糖尿病晚期勃起神经出现损伤并发生ED,推测可能与NGF分泌增加的幅度小于高血糖状态对勃起神经的损伤程度有关,也可能与NGF与其相应受体结合转运能力损害有关,给予外源性NGF可能有助于糖尿病性ED局部神经病变减轻和勃起功能改善。提示NGF的异常在糖尿病性ED的发病及治疗中可能具有重要作用。     

西黄丸及其主要成分抑制PI3K/Akt/mTOR信号通路促进PC-3荷瘤小鼠前列腺癌细胞的凋亡

目的:评估西黄丸及其主要成分对裸鼠去势抵抗性人前列腺癌PC-3细胞皮下移植瘤的PI3K/AKT/mTOR信号通路及细胞凋亡的影响.方法:通过西黄丸、麝香、牛黄、多西他赛、麝香+牛黄干预动物模型,计算各组抑瘤率及HE染色观察肿瘤细胞形态,采用qPCR方法检测各组PI3K/Akt/mTOR mRNA水平,Western印迹...     

MiR-494通过激活PI3K/AKT通路减轻大鼠肝缺血-再灌注损伤

目的探讨微小核糖核酸(miRNA)-494对肝缺血-再灌注损伤(HIRI)的影响及相关作用机制。方法 24只雄性SD大鼠随机均分为4组(每组6只):假手术组行腹部手术而未行肝脏缺血-再灌注;HIRI组大鼠行部分肝缺血60 min后,再灌注6 h;HIRI+agomir-miR-494组在术前7 d内每日腹腔注射agomir-miR-494(20μL);HIRI+agomir-NC组在术前7 d内每日腹腔注射等量的agomir-NC。采用逆转录聚合酶链反应(RTPCR)法检测各组肝组织中miR-494的信使核糖核酸(mRNA)表达水平。采用相关试剂盒检测各组的肝损伤指标和氧化应激指标表达水平。观察各组肝组织病理学改变。采用试剂盒检测各组大鼠肝组织中凋亡细胞数和胞质组蛋白相关DNA片段。采用免疫印迹法检测各组凋亡相关蛋白以及磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶(AKT)通路相关蛋白的表达量。结果 HIRI+agomir-miR-494组大鼠肝组织miR-494的mRNA水平显著高于HIRI+agomir-NC组(P0.01)。HIRI+agomir-miR-494组的血清肝损伤指标以及血清氧化应激指标均显著低于HIRI+agomir-NC组(均为P0.01)。与HIRI+agomir-NC组相比,HIRI+agomir-miR-494组肝细胞坏死明显减少和细胞完整性提高(P0.05),TUNEL阳性细胞数量明显减少(P0.05)。HIRI+agomir-miR-494组的cleaved-多聚二磷腺苷核糖聚合酶(PARP)、cleaved-含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、Bax水平明显低于HIRI+agomir-NC组(均为P0.05)。HIRI+agomir-miR-494组大鼠DNA片段显著少于HIRI+agomir-NC组(P0.01)。HIRI+agomir-miR-494组大鼠肝脏p-AKT、p-哺乳动物雷帕霉素靶蛋白(mTOR)和p-p70S6K表达量明显高于HIRI+agomir-NC组(均为P0.05)。结论 miR-494可以减轻大鼠HIRI,其作用机制与激活PI3K/AKT信号通路有关。     

黄芪多糖通过PI3K/AKT/mTOR促进激素性骨质疏松症大鼠成骨细胞增殖

目的 探讨黄芪多糖在体内外通过PI3K/AKT/mTOR信号通路对糖皮质激素诱导的骨质疏松症（glucocorticoid-induced osteoporosis,GIOP）的保护作用。方法 从分化的骨髓间充质干细胞（bone marrow mesenchymal stem cells,BM-MSCs）中培养成骨细胞,分为PBS组、模型组、LY294002组、黄芪多糖组和LY294002+黄芪多糖干预组。通过CCK-8法和碱性磷酸酶（alkaline phosphatase,ALP）染色检测细胞增殖和分化。MDC染色观察自噬体的形成。Western blot检测Beclin-1、p62等信号通路及自噬相关因子的蛋白表达。大鼠分为对照组、模型组、LY294002组、黄芪多糖组和LY294002+黄芪多糖组。比较各组大鼠的骨密度、骨组织形态学参数、组织中通路和自噬相关因子的表达。结果 黄芪多糖促进成骨细胞的增殖和分化能力（P＜0.05）。与模型组相比,黄芪多糖组PI3K/AKT/mTOR通路相关磷酸化蛋白的表达、成骨细胞的增殖分化能力、自噬体及自噬相关因子的表达均升高,但在LY294002组中发现了相反的结果（P＜0.05）。在体内实验中,与模型组相比,GIOP大鼠通过黄芪多糖干预改善了骨密度和骨形态参数,并提高了软骨组织中自噬相关因子的表达,而LY294002干预则表现出相反的结果（P＜0.05）。LY294002部分逆转了黄芪多糖对GIOP中成骨分化和骨形态参数的影响。结论 黄芪多糖通过PI3K/AKT/mTOR通路对GIOP发挥保护作用,可能与诱导自噬和促进成骨细胞增殖有关。     

NGF/MAG双基因共表达腺病毒修复大鼠周围神经损伤的实验研究

目的构建携带NGF及髓磷脂相关糖蛋白(myelin associated glycoprotein,MAG)基因序列的双基因共表达腺病毒(adenovirus expressing NGF and MAG,Ad-NGF-MAG),探讨其在大鼠坐骨神经损伤修复中的作用。方法将NGF和MAG共同克隆至5型腺病毒穿梭质粒p CA 13,并在HEK 293细胞中包装得到重组腺病毒Ad-NGF-MAG并测序鉴定。取雄性SD大鼠32只,体质量180~200 g;随机分成4组(n=8):对照组(正常对照)、空病毒组(Ad组)、单独表达NGF组(Ad-NGF组)和共表达NGF、MAG组(Ad-NGF-MAG组)。Ad组、AdNGF组和Ad-NGF-MAG组大鼠制备右侧坐骨神经损伤模型后,分别于术侧腓肠肌注射空腺病毒、Ad-NGF及AdNGF-MAG(1×108 PFU),隔天1次,共3次。对照组仅暴露右侧坐骨神经后关闭切口,术后对应时间点注射生理盐水10μL。术后31 d,分别行坐骨神经功能指数(sciatic nerve function index,SFI)、神经电生理检测;切取坐骨神经标本,行RT-PCR及Western blot检测NGF及MAG m RNA及蛋白表达水平,以及组织学观察。结果实验成功构建重组腺病毒Ad-NGF和Ad-NGF-MAG。32只大鼠术后均成活,切口Ⅰ期愈合。Ad-NGF-MAG组SFI、神经传导速度、诱发电位波幅、潜伏期均明显优于Ad-NGF组和Ad组,但未达对照组水平,比较差异均有统计学意义(P0.05)。Ad-NGF-MAG组内MAG m RNA和蛋白表达最高,NGF m RNA和蛋白表达高于对照组和Ad组,比较差异均有统计学意义(P0.05)。组织学观察显示,对照组神经连续性好,Ad组神经纤维层次混乱,Ad-NGF组神经纤维层次结构清晰,局部断端再生良好,但神经纤维结构紊乱;Ad-NGF-MAG组神经纤维生长有序,神经直径较Ad-NGF组粗,神经纤维结构良好。结论坐骨神经损伤后修复过程中,腺病毒介导NGF与MAG共表达,既可促进神经纤维生长,又可抑制神经异常分支形成,促进神经结构与功能的恢复。     

纤维蛋白胶载神经生长因子促进周围神经再生的研究

目的　探讨纤维蛋白胶 (FG)作为神经生长因子 (NGF)载体对周围神经再生的促进作用。方法　将Wistar大鼠 96只随机分为 4组 ,即对照组、FG组、NGF组、FG +NGF组 ,每组 2 4只 ,以大鼠左侧坐骨神经为修复神经模型进行实验。术后 2、4、8周进行组织学检查 ,术后 8周进行电生理检查、肌湿重检测、图像分析和透射电镜观察。结果　FG +NGF组的神经传导速度、肌张力、肌湿重、有髓纤维截面积恢复率分别为 ( 84.10± 2 .33) %、( 83 .88± 2 .96 ) %、( 6 2 .5 4± 5 .94) %、( 71.0 1± 3 .6 2 ) % ,吻合口有髓纤维通过率为 ( 6 5 .5 1± 4.5 4) % ,高于对照组、FG组 ( P <0 .0 1) ,高于NGF组 (P <0 .0 5 ) ,FG +NGF组大鼠坐骨神经再生优于单纯NGF组。结论　纤维蛋白胶可作为NGF的载体 ,用纤维蛋白胶载NGF修复周围神经损伤 ,有促进周围神经再生的作用。     

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 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.     

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.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.