多模式镇痛对下肢骨折患者术后疼痛、炎性因子及免疫功能的影响

目的：探讨多模式镇痛（MMA）对下肢骨折患者术后疼痛和炎性因子的影响。方法120例下肢骨折患者,随机均分为对照组（C组）、MMA Ⅰ组、MMA Ⅱ组、MMA Ⅲ组。C组不给镇痛,Ⅰ组仅术前给予氟比洛芬酯（经静脉）和舒芬太尼（经硬膜外）,Ⅱ组术后给药,Ⅲ组术前和术后均给药。记录术后6、12、24 h VAS评分和术前、术后24、72 h白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平和外周血CD4＋／CD8＋、CD25＋比例、NK细胞（CD3－CD16＋CD56＋）比例。结果 MMA Ⅰ组、MMA Ⅱ组、MMAⅢ组术后12、24 h VAS评分明显低于C组（P＜0．05）;MMA Ⅲ组术后24 h VAS评分显著低于MMA Ⅰ组、MMA Ⅱ组（P＜0．05）。MMAⅠ组、MMAⅡ组、MMAⅢ组术后24、72 h IL-6和TNF-α浓度明显低于C组（P＜0．05）,MMAⅠ组、MMA Ⅱ组显著高于MMA Ⅲ组（P＜0．05）;术后24、72 h MMAⅠ组、MMA Ⅱ组、MMA Ⅲ组IL-6和TNF-α浓度明显高于C组（P＜0．05）;MMA Ⅰ组和MMA Ⅲ组CD4＋／CD8＋术后72 h恢复到术前水平（P＞0．05）。MMA Ⅲ组NK细胞术后72 h恢复到术前水平,无统计学差异（P＞0．05）。术后24 h血清IL-6、TNF-α水平和外周血CD4＋／CD8＋、NK细胞水平均呈负相关关系（P＜0．05）。而术后72 h血清炎性因子和外周免疫细胞相关性不明显。结论 MMA有效改善下肢骨折患者术后疼痛,减轻炎性反应。     

白细胞滤器合用乌司他丁对大出血患者全身炎性反应的影响

目的：探讨大出血手术患者自体血回收时应用白细胞滤器联合乌司他丁对术后全身炎性反应的影响。方法选取大出血手术治疗的患者60例,随机分为A、B、C、D 4组（每组15例）,A组为对照组、B组为白细胞滤器组（ LDF组）、C组为乌司他丁组（ UTI组）、D组为乌司他丁＋白细胞滤器组（ LDF＋UTI组）。术中均使用自体血回输机,回输时B、D组均使用白细胞滤器,C、D组术中静脉滴注乌司他丁20万U,其他组给予等量0．9％氯化钠溶液静脉滴注。4组患者术中和术后连续监测血压和心率的变化。分别于术前（T1）、手术结束时（T2）、术后1 h（T3）、6 h （T4）、12 h（T5）、24 h（T6）、72 h（T7）,抽取动脉血5 ml检测白细胞计数（WBC）和中性粒细胞计数（PMN）,用酶联免疫吸附法检测血浆炎性细胞因子IL-6、TNF-α浓度水平。结果与对照组A组比较,治疗组B、C、D组各时间点血浆炎性细胞因子IL-6、TNF-α浓度随着时间进行性降低,B、C组比较无明显变化,差异无统计学意义（ P ＞0．05）,D组与其他3组比较各时间段血浆炎性细胞因子水平呈明显下降（ P均＜0．01）。结论白细胞滤器及乌司他丁具有抑制炎性细胞因子IL-6及TNF-α释放作用,两者合用效果更显著,能有效的减轻SIRS,阻断MODS的发生,能够有效的保护患者的心肺功能,有助于患者平稳的度过围术期。     

多模式超前镇痛对全膝关节置换术患者白介素-6影响的临床观察

目的：通过对全膝关节置换术后不同时间点机体应激指标血清白介素-6（IL-6）的检测,证实采用多模式联合超前镇痛较常规镇痛可以更有效的降低由手术引起的应激反应程度;从而为制定围手术期综合镇痛方案提供客观依据。方法根据入选条件选择在天津医院行择期单侧全膝关节置换术患者60例。随机单盲分成3组,分别给予腰硬联合（A组）、静脉全麻（B组）、腰硬联合复合手术前后局部浸润麻醉（C组）的不同镇痛方法。3组术后均采用静脉自控镇痛泵（ PCIA）进行术后镇痛。分别于术前1 h、术毕、术后3、24 h 4个时间点采集静脉血检测IL-6的血清含量,观察术后不良反应情况。结果3组术前血清IL-6浓度差异无统计学意义（ P ＞0．05）。术毕、术后24 h C组和A、B组比较差异有统计学意义（ P ＜0．01）;术后3 h A、C 2组,A、B 2组,差异有统计学意义（ P ＜0．01）。表明术后B、C 2组IL-6浓度均低于A组（ P ＜0．05）。以C组最为明显,各组术后不良反应情况比较,差异无统计学意义（ P ＞0．05）。结论应用多模式超前镇痛可较常规镇痛明显减轻行全膝关节置换术患者术后的应激反应,并且额外追加药物实施超前镇痛并没有增加术后不良反应的发生率。     

丹参对大鼠重症急性胰腺炎肠道微循环及炎性因子的实验研究

目的 确良观察重症急性胰腺炎（SAP）时肠道微循环血流量和内毒素、肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β及IL-6的变化以及丹参的作用.方法 将雄性SD大鼠192只,完全随机分为对照组、SAP组和治疗组各64只,各组又按模型制备后2、6、12、24 h分为4个亚组,每组16只,其中8只用于肠道血流量测定,其余8只用于抽取血样及组织学观察.以4%牛磺胆酸钠逆行胰胆管注射复制SAP模型,治疗组经颈静脉注射丹参.采用放射生物微球技术在造模后2、6、12、24 h分别测定肠道组织微循环血流量,同时检测血浆内毒素及血清TNF-α、IL-1β、IL-6,并观察肠黏膜病理改变.结果 SAP组在造模后2、6、12、24 h肠道组织血流量[分别为（0.52±0.14）、（0.43±0.04）、（0.38±0.53）、（0.33±0.47）ml/（min·g）]较对照组[分别为（1.24±0.13）、（1.27±0.27）、（1.36±0.42）、（1.14±0.63）ml/（min·g）]明显减少（P＜0.01）,血浆内毒素及血清TNF-α、IL-1β、IL-6水平较对照组明显升高（P＜0.01）,肠黏膜损伤程度较对照组明显加重（P＜0.01） 治疗组2、6、12 h肠道组织血流量[分别为（0.72±0.21）、（0.68±0.35）、（0.64±0.28）ml/（min·g）]与SAP组比较明显升高（P＜0.01）,24 h变化不明显.血清TNF-α、IL-1β、IL-6活性2、6、12 h时段与SAP组比较明显减少（P＜0.01）,24 h变化不明显.肠黏膜损伤程度较SAP组明显改善（P＜0.01）.结论 SAP时肠组织血流量减少同时伴有内毒素血症及炎性因子TNF-α、IL-1β、IL-6的升高,丹参能通过提高肠道血流量改善微循环,减轻肠道损伤.     

大黄对急性胆囊炎患者炎性反应的影响

目的探讨大黄对急性胆囊炎患者炎性反应的影响。方法70例急性胆囊炎患者按数字表法随机分成对照组和治疗组各35例,对照组给予常规治疗,治疗组在对照组治疗的基础上给予大黄粉5g吞服,3次／d,观察两组治疗前后内毒素、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-2（IL-2）水平变化。结果两组内毒索、TNF-α、IL-6在治疗后均明显下降（P〈0．05）,而治疗组的疗效更优于对照组（P〈0．05）;两组IL-2水平在治疗后均明显提高（P〈0．05）,而治疗组较对照组更明显（P〈0．05）。结论大黄能降低急性胆囊炎患者内毒素、TNF—α、IL-6水平,提高IL-2水平,从而减轻炎性反应。     

硼替佐米为主化疗方案辅以中药治疗多发性骨髓瘤骨病疗效观察

目的：探讨硼替佐米为主化疗方案辅以中药治疗多发性骨髓瘤骨病临床疗效及安全性。方法选取收治多发性骨髓瘤骨病患者共150例,以随机区组法分为A、B、C组,每组50例,分别给予VAD方案、VAD方案＋硼替佐米及VAD方案＋硼替佐米＋祛瘀散结汤治疗,比较3组临床疗效,生活质量改善率、治疗前后疼痛数字评分（NRS评分）、白介素-6（IL-6）、C-反应蛋白（CRP）水平及药物毒副作用发生率等。结果 C组患者临床疗效均显著优于A组和B组,差异有统计学意义（ P ＜0．05）;C组患者生活质量改善率均显著高于A组和B组,差异有统计学意义（ P ＜0．05）;C组患者治疗后NRS评分均显著低于A组、B组及治疗前,差异有统计学意义（ P ＜0．05）;C组患者治疗后IL-6和CRP水平均显著低于A组、B组及治疗前,差异有统计学意义（ P ＜0．05）;同时C组患者药物毒副作用发生率均显著低于A组、B组,差异有统计学意义（ P ＜0．05）。结论祛瘀散结汤辅助硼替佐米为主化疗方案治疗多发性骨髓瘤骨病可有效控制病情进展,改善生活质量,减轻疼痛程度和炎性反应水平,且有助于降低药物不良反应发生风险。     

Preemptive analgesia and effects of parecoxib on IL-6 and IL-10 expressions in burned patients

目的 探讨帕瑞昔布超前镇痛对术后镇痛及血清IL-6和IL-10水平的影响.方法 36例烧伤患者随机均分为两组:A组术毕前50 min缓慢静注帕瑞昔布40 mg;B组不施行超前镇痛.术后不行自控镇痛,在患者主诉疼痛难忍时肌注哌替啶75 mg/次.记录术后4、8、12、24 h静息VAS疼痛评分,并用放射免疫分析方法测定血清IL-6和IL-10浓度.结果 A组术后4、8、12h的VAS评分均显著低于B组(P＜0.01),血清IL-6水平低于B组,而IL-10水平高于B组(P＜0.05).结论 术毕前预用帕瑞昔布可明显减少烧伤术后疼痛和炎性反应.     

氯诺昔康用于颅脑手术后镇痛及对白细胞介素－6的影响

目的研究观察氯诺昔康用于颅脑手术后患者自控镇痛（PCA）的效果及对患者血清白细胞介素-6（IL-6）的影响。方法60例ASA Ⅰ－Ⅱ级择期颅脑手术患者，采用随机、对照的方法将患者分为三组，每组20例。A组用生理盐水作对照组；B组用氯诺昔康PCA；C组用曲马多PCA。术后患者完全清醒后静脉连接PCA泵。术后接泵即刻、术后4、12、24、48h分别记录各时间点的心率、平均动脉压、呼吸频率、血氧饱和度、VAS评分。于诱导前、术后3h、术后24h分别抽取静脉血测定各组患者血清IL-6的含量。结果B组和C组VAS评分均比A组低（P〈0．05），两组镇痛效果相近（P〉0．05）。三组患者术后血浆IL-6的值均较麻醉前升高（P〈0．05），术后3h升高的幅度无明显差异；术后24hC组和B组则有所下降，幅度无明显差异（P〉0．05）。结论氯诺昔康用于颅脑术后患者PCA是安全、有效的，能降低术后24h血浆IL-6的水平。     

急性胆囊炎患者手术前后血清炎性因子水平变化的临床意义

目的：检测急性胆囊炎患者血清白介素-8（IL-8）、白介素-15（IL-15）、超敏C-反应蛋白（hs-CRP）、内毒素、超氧化物歧化酶（SOD）手术前后水平的变化情况,并分析其意义。方法选取经临床和影像学（B超,CT）诊断确诊急性胆囊炎并行胆囊切除手术的患者300例为病例组,同时选取年龄性别相匹配的健康体检人100例为对照组。检测病例组患者术前、术后第7天及对照组血清胆固醇（TC）、三酰甘油（TG）、总胆红素（TBIL）、间接胆红素（IBIL）、钙（CA）等指标的水平;酶联免疫吸附试验（ELISA）方法检测各组血清IL-8、IL-15、hs-CRP、内毒素、SOD的水平。结果与对照组比较,病例组患者TC、TG、TBIL、IBIL、CA的水平明显高于正常对照组（ P ＜0：．05）。病例组患者术前血清IL-8、IL-15、hs-CRP、内毒素水平明显高于对照组（ P ＜0．05）;术后第7天血清IL-8、IL-15、hs-CRP、内毒素水平逐渐下降,但仍高于正常对照组（ P ＜0．05）;血清SOD水平术前则明显低于正常对照组（ P ＜0．05）,术后第7天血清SOD水平逐渐升高,但仍低于正常对照组（ P ＜0．05）。结论急性胆囊炎患者有明显的应激反应存在,持续时间较长。动态监测IL-8、IL-15、hs-CRP、内毒素、SOD水平变化有助于急性胆囊炎的严重程度的判断及临床治疗。     

乌司他丁对老年人七氟烷吸入麻醉术后认知功能的影响

目的探讨使用乌司他丁调节全身炎性反应对老年人七氟烷吸入麻醉术后认知功能的影响。方法60例择期行上腹部手术的患者随机双盲法分为持续静脉泵注乌司他丁0．2万u·kg^-1·h^-1（A组）和持续静脉泵注等量0．9％氯化钠注射液（B组）,每组30例。观察睁眼、拔管、应答时间,观察不同时间点简易精神状态量表得分及超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）、IL-10的浓度变化。结果两组患者应答时间A组少于B组（F=4．399,P=0．040）。两组患者术后1h较术前均出现了MMSE评分下降（t=7．732、11．916,均P〈0．01）,评分小于术前值超过2分,认为患者认知功能下降,但A组MMSE评分下降的幅度低于B组（F=7．582,P=0．012）;两组患者术后6h较术前均出现了MMSE评分下降（t=4．606、8．615,均P〈0．05）,A组评分小于术前值未超过2分,B组评分小于术前值超过2分,但两组闯差异无统计学意义（P〉0．05）。两组患者术后1d、3d、7d的hs-CRP、IL-6、IL-10均出现升高（均P〈0．01）,高峰出现在术后1d,术后7d仍未降至术前水平;A组术后1d、3d的hs-CRP、IL-6升高的幅度低于B组（F=14．885,P=0．000;F=4．405,P=0．040;F=18．204,P：0．000;F=8．074,P=0．006）,但A组术后1d、3d的IL．10升高的幅度高于B组（F=5．197,P=0．026;F=12．236,P=0．000）。结论乌司他丁可以促使老年人七氟烷吸入麻醉术后认知功能的快速恢复,其机制可能与其调节全身炎性反应有关。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.