肠源性内毒素血症对急性病毒性肝炎患者免疫功能的影响

目的：观察急性甲型病毒性肝炎患者内毒素对细胞免疫功能的影响及中药双利肝的临床疗效。方法：26例急性甲型病毒性肝炎患者，正常组10例为健康人，肝功能正常，各型肝炎病毒标志物均为阴性。分三组：正常组、对照组（一般用药组）、治疗组（一般用药＋双利肝组）。检测以下指标：血浆内毒素（ET）、肿瘤坏死因子－α（TNF－α）、白细胞介素－6（IL－6）、T细胞亚群和肝功能。结果：急性甲型病毒性肝炎患者，治疗前血浆ET、TNF－α、IL－6及ALT水平明显升高，治疗后明显下降；治疗前T淋巴细胞亚群CD3^ 、CD4^ 下降，CD8^ 上升，CD4^ ／CD8^ 下降，治疗后CD3^ 与CD4^ 升高，CD8^ 下降，CD4^ ／CD8^ 升高。对照组与治疗组ET、CD3^ 、CD4^ 及CD8^ 治疗前后差值比较均有明显差异（P＜0．05）。血浆中ET水平与CD3^ 、CD4^ 、CD4^ 、CD8^ 呈显著负相关，相关系数分别为－0．638（P＜0．05）、－0．676（P＜0．05）、－0．612（P＜0．05）。结论：急性甲型病毒性肝炎患者血浆内毒素水平明显升高，且与免疫功能的变化密切相关。双利肝通过降低内毒素水平，可调整机体免疫功能，达到治疗目的。     

血浆置换联合连续性血液滤过治疗急性肝衰竭

目的：研究血浆置换（PE）联合连续性静脉静脉血液滤过（CVVH）治疗急性肝衰竭（ALF）疗效及机制。方法：11例急性肝衰竭患者行PE联合CVVH治疗，治疗时间平均持续3．1d，于治疗前，PE后，CVVH6、12h，结束时分别抽血测肝肾功能、血氨、血清内毒素（ET）、TNF－α及IL－6的水平，并进行ICU监护。结果：在治疗过程中，血流动力学稳定，治疗后肝昏迷程度减轻，8例患者神志转清，清醒率为72．7％，SIRS积分从2．33分降到1．56分（P＜0．05），器官衰竭数从2．73降到1．36（P＜0．05），存活率为45．45％（5／11），肝脏病理检查发现能阻断肝细胞的进一步坏死。血浆置换后Bil-T、TBA、ET、TNF－α、IL－6明显下降（P＜0．01），凝血酶原活动度显著升高（P＜0．01）。CVVH治疗后TNF－α、IL－6、血氨、BUN、Cr呈进行性下降，而Bi1-T、TBA、ET变化不明显，与治疗前相比差异显著（P＜0．05）。结论：PE联合CVVH连续性治疗能有效清除急性肝衰竭ET和炎性介质TNF－α、IL－6水平，阻断肝细胞坏死，改善肝肾功能，在病程早期治疗能改善急性肝衰竭的预后。     

3种温病治法制剂对家兔内毒素血症治疗效果的比较

目的：比较及分析3种治疗温病的常用中医治法对家兔内毒素血症的影响。方法：采用大肠杆菌内毒素E.ColiO111:B4静注复制家兔内毒素血症模型，检测血中白介素－1（IL－1），肿瘤坏死因子－α（TNF－α）、前列环素（PGI2）、内皮素－1（ET－1）及血浆内毒素（ETX）等炎性细胞因子及血管活性介质的水平，观察清热解毒、活血化瘀、养阴增液3种温病治法制剂对内毒素血症的治疗效果。结果；静注内毒素0．5小时后模型组动物体温急剧上升，IL－1、TNF－α、ET－1、ETX水平均明显升高，PGI2下降，与正常组比较均有显著性差异（P均＜0．05）。与模型比较，3个治疗组给予药物治疗后发热症状得到明显的改善，清热解毒组和养阴增液组血浆IL－1、TNF－α、ET－1水平均明显降低（P均＜0．01），而PGI2显著升高（P均＜0．05），活血化瘀组IL－1水平下降不明显，TNF－α水平略有上升，但其ET－1、PGI2改变均非常显著（P均＜0．01）；3个治疗组ETX水平无明显变革。结论：3例温病治法制剂对内毒素血症均有明显的改善作用，但其作用途径可能不一致，分别通过拮抗内毒素所诱生炎性细胞因子及血管活性介质而阻止毒素血症的进展。     

补锌对重型烧伤患者细胞因子的影响

目的：探讨补锌对重型烧伤患者细胞因子水平的影响。方法：对32例重型烧伤患者随机分为治疗组（A），组服用葡萄糖酸锌口服液，口服等渗盐水为对照组（B组），于伤后当天开始用药，持续28d，检测伤后1、3、14和28d时血清内毒素，肿瘤坏死因子－α（TNF－α）和白细胞介素－6（IL－6）含量。结果：（1）在伤后1、3d,2组间血清内毒TNF－α和IL－6水平无明显差别（P＞0．05）。（2）在伤后14d及28d，A组血清内毒素、TNF－α和IL－6含量显著低于B组。结论：补锌能降低重型烧伤患者细胞因子的水平。减轻烧伤后全身炎症反应综合征（SIRS）和多器官功能障碍综合征（MODS），提高治愈率。     

维拉帕米对重症急性胰腺炎大鼠肺损伤的保护作用

目的：探讨钙通道阻滞剂维拉帕米对重症急性胰腺炎（SAP）大鼠肺损伤的影响。方法：wistar大鼠45只，随机分为假手术组、SAP组和维拉帕米治疗组，观察动物血清中白细胞介素－1（IL－1）、白细胞介素－6（IL－6）和肿瘤坏死因子－α（TNF－α）的含量，肺组织病理学变化。结果：SAP时，大鼠血清中IL－1、IL－6和TNF－α的含量均显著升高（P＜0．01），肺损伤严重，维拉帕米治疗组炎性细胞因子水平显著下降（P＜0．05），肺病理损害程度显著减轻（P＜0．05）。结论：维拉帕米可抑制SAP大鼠炎性细胞因子IL－1、IL－6、TNF－α的产生释放，减轻肺损伤的程度。     

重型肝炎患者血清TNF—α的变化及临床意义

目的：通过观察各期重型肝炎患者血清TNF－α的水平及其在ALSS治疗前后的变化,探讨TNF－α在重型肝炎发病中的作用机制及临床意义。方法：设重型肝炎组,急性肝炎组,慢性肝炎组,肝炎后肝硬化组和正常对照组,测定每组血清TNF－α,内毒素,TGF－β1的水平,以及重型肝炎组患者血清TNF－α,内毒素,TGF－β1在ALSS治疗前后的水平。结果：重型肝炎组患者血清TNF－α（等精性因子水平明显高于急性肝炎组,慢性肝炎组,肝炎后肝硬化组和正常对照组,ALSS治疗后,重型肝炎患者血清TNF－α等炎性明显低于治疗前水平。TNF－α逐渐下降的重型肝炎患者。病情逐渐好转。结论：高水平的TNF－α在重型肝炎患者肝细胞损伤中起着重要作用。ALSS治疗可清除TNF－α对重型肝炎有明显疗效,血清TNF－α水平的变化趋势对评估重型肝炎的疗效及预后有一定意义。     

急性腔隙性脑梗塞脑底动脉血流变化与血浆IL—6及TNF—α关系的临床研究

目的：探讨急性腔隙性脑梗塞患脑底动脉血流变化与血浆白介素6（IL－6）及肿瘤坏死因子－α（TNF－α）关系。方法：对110例急性腔隙性脑梗塞患通过经颅多普勒超声（TCD）检测分成脑动脉狭窄组及脑动脉供血不足组，计算脑血管搏动指数（PI）及阻力系数（RI），并进行血浆IL－6及TNF－α测定，与40例正常人做对照，结果：脑动脉狭窄组的PI、RI及血浆IL－6及TNF－α的含量明显高于对照组（P＜0．01）。较脑动脉供血不足组显增高（P＜0．05）。脑动脉供血不足组血浆IL－6及TNF－α含量较对照组显增高（P＜0．05）。结论：急性腔隙性脑梗塞患脑底动脉血流变化与血浆IL－6及TNF－α水平密切相关，脑底动脉狭窄较脑底动脉供血不足脑组织缺血坏死程度及炎性反应更明显，更应引起临床高度重视。     

内毒素血症时肝组织内促炎因子抗炎因子的变化及其与肝损伤的关系

目的：观察内毒素性肝损伤过程中肝组织内致炎因子肿瘤坏死因子－α（TNF－α）、白介素－6（IL－6）和抗炎因子IL－4、IL－10的变化规律及其与急性肝损伤的关系。方法：建立小鼠内毒素肝损伤模型，酶联免疫吸附法（ELISA）检测肝组织内TNF－α、IL－6、IL－4和IL－10的水平，同时观察肝损伤程度。结果：内毒素肝损伤过程中，肝组织内TNF－α和IL－6水平显著升高，均与内毒素呈明显的量效关系，肝组织内抗炎症介质IL－4和IL－10的水平也显著增高，抗炎症介质的释放要迟于致炎症介质，且随着内毒素剂量的增大，抗炎症介质的释放进一步延迟，峰值后移；随着内毒素剂量的增大，血浆丙氨酸转氨酶（ALT）和总胆红素（TBIL）进一步升高，肝组织结构受损进一步加重。结论：内毒素致肝损伤后，肝组织内抗炎症介质的释放要迟于致炎症介质；抗炎症介质释放的延迟可能是导致致炎反应和抗炎反应失衡的原因，是内毒素肝损伤的重要机制。     

全身炎症反应综合征患者致炎因子与抗炎因子的变化及相关性研究

目的 观察全身炎症反应综合征（SIRS）患者血浆中致炎因子肿瘤坏死因子－α（TNF-α）、白介素－6（IL－6）和抗炎因子转化细胞生长因子－β（TGF-β）、白介素－10（IL－10）的变化规律及其相关性。方法 符合SIRS诊断48例，分别在入院后第1、8小时和第2、3、4天清晨空腹抽肘静脉血3mL，测定TNF－α、IL－6、TGF－β和IL－10，并设对照组。结果 TNF－α和IL－6各监测点均比对照组显著升高（P＜0．05，P＜0．01），TGF－β和IL－10入院后第小时与对照组比较无显著差异，第8小时以后各监测点均比对照组显著升高（P＜0．05，P＜0．01），TNF－α和IL－6峰值出现早于TGF－β和IL－10，致炎因子与抗炎因子具有显著的相关性。结论 拮抗炎症因子的同时提高机体免疫功能，达到致炎因子与抗炎因子的平衡是治疗SIRS的新思路。     

急性心肌梗死与再灌注后血浆肿瘤坏死因子α、白细胞介素-6的变化

目的：观察急性心肌梗死（AMI）再灌注治疗患者血浆肿瘤坏死因子α（TNF－α）、白细胞介素－6（IL－6）浓度的动态变化评价其意义，方法：对发病6h内AMI患者48例进行溶栓治疗。测定患者溶栓前、溶栓后0．5、1、2、4、12、48h及1周血浆TNF－α、IL－6浓度。结果：36例再通，12例未通。溶栓前TNF－α、IL－6浓度都升高。溶栓后未通组TNF－α、IL－6均于48h达高峰。峰值都大于再通组。再通组TNF－α高峰不明显。IL－6于12h达峰后回落。结论：AMI患者血浆TNF－α、IL－6动态变化反映AMI炎性反应。再灌注挽救心肌而减轻的炎症足以抵消再灌注损伤。     

Fresh-frozen plasma, pathogen-reduced single-donor plasma or bio-pharmaceutical plasma?

Three types of therapeutic plasma are available that differ in their manufacturing processes, composition, clinical efficacy, and side effects. Quarantine-stored, not pathogen-reduced fresh-frozen plasma (QFFP) is prepared from single whole blood or plasma donations. The manufacture of pathogen-reduced single-donor plasmas such as methylene blue-light treated (MLP) or amotosalen-ultraviolet light treated plasma (ALP) involves the addition of a chemical followed by irradiation and subsequent removal of the chemical. Both plasma types show substantial fluctuation of clotting factor and inhibitor levels according to interindividual variations, and both carry the risk of inducing transfusion-associated lung injury (TRALI). Photo-oxidation in pathogen-reduced single-donor plasmas reduces clottable fibrinogen and other clotting factors markedly, and there is a lack of clear evidence showing whether this is harmful or not. MLP also appears to be less effective clinically than QFFP. Like clotting factor or inhibitor concentrates, solvent/detergent-treated plasmas (SDP) are bio-pharmaceutical preparations derived from large plasma pools, and variations in plasma protein levels from batch-to-batch are for that reason low. The SD manufacturing process inevitably involves a considerable reduction of plasmin inhibitor (PI), and moderate reduction of all other clotting factors and inhibitors in the final plasma bags. Clinical studies and broad clinical use have however shown that this does not significantly reduce clinical efficacy or increase adverse events. SDPs obviously do not induce TRALI and the risk of allergic reactions is significantly lower than for QFFP. Common to all three plasma types is that the time between donation and freezing the plasma, and whether plasma from whole blood or apheresis plasma is used as starting material, are decisive determinants for the clotting factor and inhibitor potencies in the final bags. Plasma frozen 3-6h after donation, and apheresis plasma, contain markedly greater amounts of clotting factors and inhibitors than plasma frozen 15-24h after collection or plasma from whole blood. Lyophilisation and the pooling of single-donor plasma units with ABO blood group in suitable proportions (Uniplas) facilitate SDP handling and logistics without loss of clinical efficacy. SDP is obviously at least as cost-effective as QFFP if non-infectious adverse events including TRALI are taken into account, at least in younger patients and patients with good prognosis.     

Dissemination of contact activation in plasma by plasma kallikrein

The dissemination of contact activation of plasma was examined by measuring the cleavage of Hageman factor (HF) molecules on two separate sets of kaolin particles, one of which contained all of the components of the contact activation system, HF, prekallikrein (PK) and high molecular weight kininogen (HMWK) in whole normal plasma, and the second set of particles containing only HF and HMWK, being prepared with PK-deficient plasma. After mixing of the particles, cleavage of HF on the second set of particles occurred at a rate similar to that occurring on the first set of particles. This indicated that rapid dissemination and burst of activity of the contact reaction takes place in fluid phase. A supernatant factor, responsibel for the dissemination of the contact reaction, was identified as kallikrein. A rapid appearance of cleaved PK (kallikrein) and HMWK on both the kaolin surface and in the supernate was observed. Within 40 s, > 70-80% of the PK and HMWK in the supernate was cleaved. On the surface, approximately 70% of each radiolabeled protein was cleaved at the earliest measurement. Cleavage of PK by activated HF occurred at least 17 times faster on the surface than in the fluid phase, as virtually no cleavage of PK occurred in fluid phase. Each molecule of surface-bound, activated HF was calculated to cleave at a minimum, 20 molecules of PK per minute. It is concluded that the contact activaton of plasma may be divided into three phases: (a) the reciprocal activation of a few molecules of zymogen HF and PK on the surface, with HMWK acting as cofactor to bring these molecules into apposition; (b) the rapid release of kallikrein into the fluid phase and the continued conversion of PK to kallikrein by each surface-bound molecule of activated HF; and (c) the activation by fluid-phase kallikrein of multiple surface-bound HF molecules, and the cleavage of multiple molecules of MHWK both in fluid phase and on the surface by the soluble kallikrein. The evidence suggests that steps b and c account for a great majority of the generation of contact activation of plasma.     

Range of fractionated plasma products to optimize plasma resources

<正>HUMAN PLASMA is a source material that is crucial for the production of unique therapeutic fractionated products.Indeed,plasma contains hundreds of proteins ensuring many physiological functions.The most abundant proteins,albumin and immunoglobulin G (IgG),are present at about 35 and 10 g/L,respectively,representing about 80% of all plasma proteins.However,other important therapeutic proteins include the coagulation factors (factor Ⅷ (FⅧ); FⅨ; Von Willebrand Factor (VWF),fibrinogen) various protease inhibitors (alpha 1-antitrypsin; antithrombin; C1-esterase) and anticoagulants (protein C) which exhibit potent physiological activity.Currently over 10 different protein therapeutics can be extracted from plasma to treat life-threatening diseases or injuries associated to bleeding and thrombotic disorders,immunological diseases,infectious conditions as well as tissue degenerating diseases,thus addressing the clinical needs of many patients.Considering that plasma is a very valuable resources available in limited supply at national levels,it is important,for ethical,medical,and economical reasons,to optimize its use by producing,at satisfactory yields,an appropriate range of safe products meeting the needs of patients.     

Partial plasma protein replacement in therapeutic plasma exchange

We wished to determine whether subtotal replacement of protein in plasma removed at plasma exchange would be adequate to prevent hypovolemia and hypoproteinemia. Seven well nourished outpatients with chronic progressive multiple sclerosis underwent 60 plasma exchanges in which two liters of plasma were replaced with 750 ml saline followed by 1250 ml of a 5% albumin solution (62.5% albumin replacement). Total serum protein, protein electrophoresis, and immunoglobulin levels were measured before and after each exchange. Clinically, the exchanges were well tolerated. Total serum protein dropped by a mean of only 18% during the study and mean preexchange serum albumin levels were unchanged, even though immunoglobulins decreased by 57–72%. We conclude that in well nourished patients, partial albumin replacement of this magnitude is an adequate substitute for plasma removed in a plasma exchange.     

The efficacy of plasma exchange in the removal of plasma components

The efficacy of plasma exchange in the removal of immunoglobulins (IgG, IgM, IgA), complement components (C1q, C4, C3), alpha 1-antitrypsin, alpha 2-macroglobulin, and transferrin was studied by analysis of pre- and postexchange serum samples and the plasma removed both in a healthy volunteer and in five patients undergoing therapeutic plasma exchange. In the healthy volunteer, the measured reduction in serum concentration and the measured amount removed for each component was compared with values predicted by a physical model. For all components except IgM, the sum of the measured amount removed during the procedure and the calculated amount present in the circulation progressively exceeded the calculated intravascular amount present before plasma exchange. This was particularly the case for C4, C3, alpha 1-antitrypsin, and alpha 2-macroglobulin and may be explained by influx from the extra- to the intravascular compartment during the procedure. Influx also occurred in the patients. We conclude that, except for IgM, the actual amount of a component that has been removed should be assessed for proper evaluation of the efficacy of PE.     

The concentration of plasma fibronectin in burns patients treated with fresh frozen plasma or plasma protein fraction

A group of 10 patients with 30-70% burns were given intravenous infusions during the first 48 h following hospital admission either with fresh frozen plasma (FFP) or human plasma protein fraction ( HPPF ). FFP contained 300-400 mg/dl plasma fibronectin whereas none was detectable in HPPF . Circulating plasma fibronectin levels fell quickly in those patients receiving HPPF and levels remained low for 2-3 weeks. In those receiving FFP, plasma fibronectin remained normal during the 48-h transfusion period but fell subsequently. Fibronectin may be an important determinant in the resistance to shock and infections. Consideration should therefore be given to the use of blood products which contain fibronectin and to the monitoring of plasma levels both during the acute and recovery periods after burn injury.     

Influence of plasma exchange pheresis on plasma elimination of ceftriaxone.

The plasma elimination rates of serial 2-g intravenous injections of ceftriaxone were studied in a patient who also was treated with therapeutic plasma exchange pheresis. Plasmapheresis had negligible influence on the total clearance of ceftriaxone.     

磁处理不同溶液对血浆中某些生化指标的影响

采用调磁、静磁场处理不同溶液测定血浆生化指标,探讨其影响机理,指导临床。方法用正常人血浆,实验分对照组、调磁组、静磁组,各组用同份血浆,每组设测定管,标准管,测K 、Na 。P、BUN、MMS、血糖、CK、LDH、GPDA等测得数据经统计学处理后进行分析比较。结果静磁场和调磁场处理溶液均能显著降低GPDA的活性,但调磁场的作用极为显著。两种磁场均能使血浆Na 含量降低,而静磁场对BUN测定时呈色反应具有显著的影响,校对照组和调磁场组的颜色明显谈浅。结论两种磁场均可升高血浆K 含量和降低Na 的含量,调磁场磁化溶液可显著低GPDA的活性,而静磁场磁化溶液可显著升高CK、LDH的活性降低GPDA的活性。同时观察到调磁场对GPDA的活性有极强的抑制作用。静磁场使BUN测定时的呈色反应明显变浅．而调磁场却不明显,另外,静磁场和调磁场均具有显著降低血浆MMS效应。