靶向中期因子反义寡核苷酸的体内抗肿瘤双应

目的 观察靶向中期因子反义寡核苷酸的体内抗肿瘤效应.方法 构建人肝癌裸鼠原位移植瘤模型48只,随机分6组,生理盐水对照组,MK-AS(每日25、50、100mg/kg)组,MK-Sen(每日50mg/kg)组和5-Fu(每日10 mg/kg)组,放免法检测血清AFP浓度,Western blot检测组织MK、p53、bax、bcl-2和Caspase-3蛋白水平.结果 (1)与生理盐水对照组比较,MK-AS治疗组的肿瘤体积明显减小,[(807.75±195.19)mm3比(552.75±84.38)、(532.00±121.57)、(294.50±70.66)mm3],差异有统计学意义(P<0.01);(2)MK.AS治疗组的肿瘤瘤重与生理盐水对照组比较显著降低,[(1.29±0.13)g比(0.70±0.14)、(0.64±0.18)和(0.44±0.18)g],差异有统计学意义(P<0.01);(3)MK-AS明显下调肿瘤组织MK和bcl-2蛋白的表达,而p53、bax、Caspase-3表达上调.结论 MK-AS具有明显的体内抗肿瘤效应;MK-AS的抗肿瘤效应可能与凋亡相关蛋白p53、bax、Caspase-3表达水平的上调和bcl-2的下调有关.     

凋亡相关基因 bcl-2、bax、bad与乳腺癌

目的探讨乳腺癌发生、发展过程中bcl-2、bax及bad基因表达水平变化及与乳腺癌其他生物因素的相关性。方法复习国内、外相关文献并进行综述。结果在从正常乳腺组织到乳腺癌逐渐演化的过程中凋亡抑制基因bcl-2的表达水平变化尚有待进一步研究,而凋亡促进基因bax、bad的表达水平呈递减趋势。bcl-2基因表达水平与乳腺癌中一些公认的正性因子如雌激素受体(ER)、孕激素受体(PR)呈正相关,与其他一些负性因子如p53、表皮生长因子受体、c-erbB-2、腋窝淋巴结转移情况等呈负相关。bax基因的表达水平与乳腺癌ER、PR水平以及p53表达水平等无关。对于bad基因与乳腺癌其他生物因素的相关性尚未见报道。结论乳腺癌中bcl-2基因表达水平的变化对乳腺癌预后以及治疗的作用尚存在争议,bad基因与乳腺癌预后的关系亦不清楚,而bax基因表达水平与乳腺癌的预后呈正相关。对于它们的研究将为我们评价乳腺癌的预后提供新的指标,为乳腺癌的治疗开辟新的思路。     

在非何杰金胃淋巴瘤患者中bax,bcl-2和p53蛋白表达的预后意义

原发性胃淋巴瘤是一种罕见的肿瘤,在所有胃肿瘤中所占比率不到5%。研究表明近10年其发病率有所增加。已证实多种基因与胃淋巴瘤的病因有关,其中包括p53、bcl-2、bax和c-myc。p53蛋白的突变属于最常见的人体恶性肿瘤基因变化,bcl-2蛋白的表达也见于淋巴瘤、上皮肿瘤和淋巴组织,bax蛋白的表达可诱导凋亡。在此项研究中,作者从病理学与临床表现分析p53、bcl-2和bax基因的相互表达以及这些基因在36例原发性胃淋巴瘤胃切除术后的预后价值。雅典大学Hippocration医院外科曾于1990～1995年间收治36例胃淋巴瘤,计男21例,女15例,平均年龄58岁(33～82…     

羟基磷灰石纳米粒子肝动脉灌注对兔VX2肝种植瘤生长和bax/bcl-2蛋白表达的影响

目的 探讨羟基磷灰石纳米粒子（NanoHAP）在体内对兔VX2肝种植瘤生长的抑制作用及对肿瘤细胞bax／bcl-2凋亡蛋白表达的影响。方法 将56只VX2肝荷瘤兔随机分成四组，通过肝动脉灌注NanoHAP溶胶、5-Fu以及5-Fu与NanoHAP的混合液，并与生理盐水组对照。观察各组动物的一般情况，对肿瘤体积进行监测并比较。采用免疫组织化学染色观察bax／bcl-2蛋白的表达。结果 各治疗组对肿瘤生长都有明显的抑制作用。NanoHAP溶胶组肿瘤体积明显小于对照组（P〈0．05），肿瘤生长抑制率达到28．1％；5-Fu组抑瘤率达到43．7％，但动物表现出明显毒副作用；联合治疗组抑瘤率达到51．2％，而且毒副反应明显小于5-Fu组。NanoHAP组及联合治疗组免疫组织化学染色显示bcl-2蛋白表达率分别为41．7％（5／12）、38．5％（5／13），较对照组72．7％（8／11）明显降低；bax蛋白表达率为50．0％（6／12）、61．5％（8／13），明显高于对照组127．3％（3／11）。结论 NanoHAP在体内对兔VX2肝种植瘤生长有明显的抑制作用，而且能明显降低5-Fu的毒性作用。其抑瘤机制可能是通过影响bax／bcl-2的表达加速肿瘤细胞凋亡。     

对成骨性肿瘤及瘤样病变bcl-2表达的分析

目的探讨bcl-2基因蛋白在成骨性肿瘤及瘤样病变中表达的方式和意义.方法免疫组织化学染色,对骨肉瘤、骨化性纤维瘤、骨纤维结构不良及骨痂组织中PCNA、p53、Fas和bcl-2蛋白检测,对其表达与肿瘤转移、组织形态学等指标进行比较分析.结果 PCNA和p53在低分化骨肉瘤中呈高表达,bcl-2在高分化骨肉瘤及骨化性纤维瘤中呈高表达.PCNA和p53与bcl-2均高表达者肿瘤发生转移的机率较高,而仅bcl-2高表达者预后较好.结论成骨性肿瘤中良性与高恶性的发病机制有所不同bcl-2高表达导致异常细胞因生存期延长而过度积累可能是良性和低度恶性肿瘤的主要发病机制.恶性肿瘤的主要发病机制则可能是多种基因异常共同作用的结果.     

乳腺癌p53，ki-67和bcl-2的表达与新辅助化疗的关系

目的 研究乳腺癌p53,ki-67和bcl-2基因蛋白表达与新辅助化疗临床效果的关系,以寻找指导治疗、判断预后的生物学指标.方法 采用免疫组化SABC法测定118例可手术的乳腺癌标本的p53,ki-67和bcl-2的蛋白表达,并分析其与新辅助化疗疗效的关系.结果 术前辅助化疗有效率为68.6%.p5 3表达阳性,化疗效果差（P＜0.05）;而ki-67阳性表达者有效率明显高于ki-67不表达者（P＜0.05）;bcl-2表达与疗效无明显关系.p53蛋白阳性表达者bcl-2表达下降.p53与ki-67蛋白表达有明显关系.结论 p53和ki-67蛋白表达可作为指导新辅助化疗及预后判断的分子生物学指标.     

乳腺癌患者高危型人乳头状瘤病毒感染、p53蛋白表达及淋巴结转移分析

目的分析乳腺癌患者高危型人乳头状瘤病毒（HPV）感染、p53蛋白表达和淋巴结转移率。 方法选取2016年5月至2018年5月于西北妇女儿童医院治疗的乳腺癌患者共90例作为观察组,选取同期于本院治疗乳腺增生患者90例作为对照组。对癌组织行HPV基因分型和p53蛋白检测,增生组织行HPV基因分型。观察入组患者高危型HPV感染率,分析乳腺癌患者肿瘤大小、TNM分期、淋巴结转移率与p53蛋白表达等。 结果观察组患者中共60例发生高危型HPV感染,对照组中共36例发生高危型HPV感染,观察组患者中HPV16、18基因型感染率分别为21.11%（19/90）和22.22%（20/90）,均高于对照组[2.22%（2/90）和2.22%（2/90）],差异均有统计学意义（χ² = 7.108、P = 0.001,χ² = 8.063、P = 0.001）。观察组HPV阳性患者淋巴结转移率为93.33%（56/60）,显著高于HPV阴性患者（21/30、70.00%）,差异有统计学意义（χ² = 4.072、P = 0.002）。观察组患者中p53蛋白阳性者39例（39/90、43.33%）,其中肿瘤大小≤ 2 cm者27例（27/39、69.23%）、TNM分期Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期分别占15.38%（6/39）、30.77%（12/39）、35.90%（14/39）和17.95%（7/39）,淋巴结转移率为82.05%（32/39）;p53蛋白阴性患者51例（51/90,56.67%）,肿瘤大小≤ 2 cm者35例（35/51、68.63%）、TNM分期Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期分别占7.84%（4/51）、19.61%（10/51）、49.02%（25/51）和23.53%（12/51）,淋巴结转移率为86.27%（44/51）,p53蛋白阴性组与p53蛋白阳性组患者肿瘤大小、TNM分期及淋巴结转移率差异均无统计学意义（χ² = 0.682、P = 0.462,χ² = 0.491、P = 0.507,χ² = 0.572、P = 0.461）。 结论检测乳腺癌患者高危型人乳头状瘤病毒感染、p53蛋白表达及淋巴结转移率有助于对乳腺癌的诊疗;p53蛋白阳性率下降可能促进HPV感染相关肿瘤的发生和发展。     

乳腺癌病理生物学特性与多肿瘤基因表达的关系

目的 观察多肿瘤基因在乳腺癌组织中的表达,探讨其与乳腺癌病理生物学特性的关系.方法 采用免疫组织化学SP染色法对120例乳腺癌组织中多肿瘤基因的表达进行检测[雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(C-erB-2)、p53、转移抑制基因(mn23)、bcl-2、增殖细胞核抗原(PCNA)、多药耐药蛋白(MRP)],分析其与乳腺癌病理生物学特性的关系.结果 p53、bcl-2的表达在不同乳腺癌激素受体状态中差异有统计学意义,且与ER、PR的表达有显著相关性:p53在ER(-)、PR(-)的乳腺癌中呈现高表达,在ER(+)、PR(+)的乳腺癌中呈现低表达(P<0.01);而bcl-2则相反(P<0.01).bcl-2的表达与月经状态有关,在绝经前乳腺癌组织中的表达明显高于绝经后乳腺癌(P<0.01).PCNA的表达与肿瘤的大小相关,在直径较大的肿瘤(>3 cm)中的表达显著高于直径较小的肿瘤(≤3 cm,P<0.01).结论 p53、bcl-2的表达与ER、PR的状态相关,可作为判断乳腺癌生物学特性和预后的重要指标.     

肝癌bcl-2基因异常及与p53蛋白表达的关系

为探讨bcl-2和p53基因与肝细胞癌的关系，采用半套式原位聚台酶链反应和免疫组化技术原位检测40例肝细胞癌中bcl-2／JH融合基因、bcl-2蛋白及突变型p53蛋白的表达。结果显示40例肝细胞癌中6例bcl-2蛋白阳性，发生bcl-2基因重排10例，25例p53蛋白阳性，bcl-2蛋白表达与bcl-2／JH融合基因间无相互相对应关系。p53蛋白与bcl-2蛋白表达及bcl-2基因重排间无明显关系。结果说明，bcl-2和p53基因均与肝细胞癌的发生有一定关系。bcl-2／JH融合基因不是引起bcl-2蛋白表达的唯一原因。bcl-2和p53基因在肝细胞癌变过程中无协同作用。     

新辅助化疗对结肠癌细胞凋亡及相关调控蛋白表达的影响

目的 观察新辅助化疗(NACT)对结肠癌细胞凋亡及相关调控蛋白表达的影响.方法 收集结肠癌患者114例,采用原位末端标记法和免疫组织化学方法分别观察经NACT的FOLFOX4方案治疗前后结肠癌细胞凋亡和癌组织中B细胞淋巴瘤/白血病-2相关X蛋白(bax)、B细胞淋巴瘤/白血病-2(bcl-2)、环氧合酶-2(COX-2)、p53蛋白的表达,并判定NACT的近期疗效.结果 NACT化疗后结肠癌细胞发生典型凋亡形态学变化,细胞凋亡系数(3.87％比1.17％)和凋亡阻性率(59.65％比23.68％)显著高于化疗前.经NACT治疗后患者结肠癌细胞bcl-2(54.39％比70.15％)、COX-2(28.07％比50.00％)和p53(45.61％比70.05％)的阳性表达率与化疗前比较均有不同程度降低,差异有统计学意义(P＜0.05或P＜0.01),而bax阳性表达率(22.81％比50.88％)显著增强,差异有统计学意义(P＜0.01).同时bcl-2/bax比值(3.08比1.07)也显著降低.NACT治疗组的总有效率(39.47％)显著高于对照组(1.75％),治疗后患者无严重药物不良反应.结论 结肠癌患者经NACT化疗后癌组织中bcl-2、COX-2和p53蛋白表达明显降低,而bax蛋白的表达显著增加,促进癌细胞凋亡,且NACT的近期疗效显著.     

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.     

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.     

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.     

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.