Effects of antimicrobial agents on spontaneous and endotoxin-induced cytokine release of human peripheral blood mononuclear cells

 Because the immunomodulatory effects of antibiotics could possibly influence the degree of the systemic and local response to infection, knowledge of their intrinsic influence on the host's inflammatory response appears to be essential. Therefore, this study investigated the effects of frequently used antimicrobial agents (β-lactams, quinolones gentamicin, vancomycin and metronidazole) on the in-vitro tumor necrosis factor (TNF)-α and interleukin (IL)-6 production of isolated human peripheral blood mononuclear cells (PBMNC), cultured with or without endotoxin, in comparison with those effects obtained in a whole-blood assay system. In the presence of ciprofloxacin, ofloxacin, gentamicin, vancomycin, and metronidazole, a significant inhibition of the endotoxin-stimulated TNF-α production of human peripheral blood mononuclear cells (PBMNC) was found at therapeutic levels. Only ofloxacin showed a significant inhibitory influence on the endotoxin-induced IL-6 production of PBMNC. In the whole-blood assay, significant effects were not detectable. None of the antibiotics showed cytotoxicity. It is concluded that, at present, the direct immunological effects of antibiotics should be interpreted carefully with regard to the experimental conditions, and regardless of the therapeutic implications. To assess the potential direct immunomodulatory effect of antimicrobial agents, different cell culture procedures should be used. Received: October 19, 2001 / Accepted: February 15, 2002     

青少年特发性胸椎侧凸患者的脊髓偏移及临床意义

[目的]揭示青少年胸椎特发性侧凸患者椎管内脊髓的偏移，明确其变化趋势，并探讨其可能的发生机制和临床意义。[方法]本研究包括39名以右胸弯为主弯的青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）患者。测量主胸弯节段内（T5-12）椎管内脊髓与凸凹侧椎弓根之间的距离，计算脊髓的偏移，揭示其变化趋势，并分析顶椎区脊髓偏移与主胸弯Cobb＇s角和顶椎相对偏移之间的相关性。[结果]在T5-12节段椎管内，脊髓与凸侧椎弓根之间的距离显著大于与凹侧椎弓根之间的距离（P〈0．05），即脊髓向凹侧椎弓根偏移，且以顶椎区最为显著，而逐渐向两侧端椎区递减。顶椎区脊髓偏移与主胸弯Cobb’s角和顶椎相对偏移存在显著的正相关（相关系数分别为0．631和0．546）。[结论]胸椎特发性脊柱侧凸患者存在侧凸节段椎管内脊髓偏移的现象，且以顶椎区最显著。研究结果提示脊髓偏移可能与脊椎偏移后凹侧脊神经的牵拉有关，而且凹侧置钉的风险高于凸侧。     

神经干细胞静脉移植治疗脊髓损伤的实验研究

[目的]观察神经干细胞静脉移植对损伤大鼠脊髓功能的治疗作用。[方法]取孕14—16dSD胎鼠的脑室下区组织，体外培养后鉴定细胞。制作脊髓全切模型，伤后1周将Brdu标记好的神经干细胞通过尾静脉注射移植到大鼠体内，移植后及8周行皮层体感诱发电位（CSEP）检测和BBB功能评分，并留损伤脊髓处作病理切片及免疫组化染色。[结果]（1）移植后8周BBB评分损伤组、移植组都有所恢复，但都未达到正常水平，移植组恢复较好；（2）模型制作后，CSEP波均消失，细胞移植后8周移植组的波形有不同程度的恢复，但潜伏期延长；（3）移植组大鼠脊髓损伤处存在大量Brdu染色阳性细胞，表明移植的细胞在体内可到达损伤脊髓处并能存活；脊髓损伤部位NF-200及GFAP染色阳性的细胞表明移植的细胞可以分化为具有神经元和胶质细胞特性的细胞。[结论]静脉移植的神经干细胞能到达损伤区代替受损的神经元及神经胶质细胞，使损伤的脊髓功能得到一定程度的恢复。     

推拿治疗老年高血压及对动态血压负荷的影响

目的研究推拿治疗老年高血压及对动态血压负荷的影响。方法选择60例轻、中度高血压患者，随机分为推拿治疗组30例，药物对照组组30例。结果推拿治疗组总有效率为83．3％。药物对照组为86．7％；治疗组主要症状疗效前后对比有显著性差异（p〈0．05），治疗组治疗后动态血压负荷值明显降低，较治疗前差异有显著性（p〈0．01，p〈0．05）。结论推拿治疗老年高血压疗效显著，推拿可降低动态血压负荷。     

Blood velocity assessment using 3D bright-blood time-resolved magnetic resonance angiography.

Blood velocity is a functional parameter that is not easily assessed noninvasively, especially in small animals. A new noninvasive method that uses magnetic resonance angiography (MRA) to measure blood flows is proposed. This method is based on the time-of-flight (TOF) phenomenon. By initially suppressing the signal from the stationary spins in the area of interest, it is possible to sequentially visualize only the signal from the moving spins entering a given volume. With this method, 3D cine images of the blood flow can be generated by positive contrast, with unparalleled spatial (<200 microm) and temporal resolutions (<10 ms/image). As a result, it is possible to measure flow in sinuous paths. The present method was applied in vivo to measure the blood velocity in mouse carotid arteries. Because of its robustness and simplicity of implementation, this method has numerous potential applications for fundamental studies in small animal models.     

Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

近红外光谱仪监测窒息新生儿听觉刺激诱发时的脑氧合代谢及脑血流变化

目的了解窒息新生儿在听觉刺激诱发脑神经活动时的脑氧合代谢和脑血流量的改变。 方法1998~2003年北京中日友好医院儿科选择窒息新生儿34例为窒息组，健康新生儿40名为对照组。使用近红外光谱仪，观察听觉刺激试验诱发的脑氧合血红蛋白\[Hb O2\]、还原血红蛋白\[Hb H\]和总血红蛋白\[Hb tot\]浓度的变化，并比较两组脑氧合代谢和脑血流量的改变。根据\[Hb O2\]、\[Hb H\]和\[Hb tot\]不同的变化，将氧合代谢曲线分为A(\[Hb O2\]、\[Hb H\]和\[Hb tot\]均增加)； B(\[Hb O2\]和\[Hb tot\]增加,\[Hb H\]降低)；C(\[Hb O2\]和\[Hb tot\]降低,\[Hb H\]增加)3种曲线类型。 结果窒息组中25例(25/34、73.5%)显示C型变化，对照组中28例(28/40、70.0%)显示A型变化，两组中A、C两型例数比较差异显著(P<0.05)。两组\[Hb O2\]和\[Hb tot\]数值变化幅度比较差异显著(P<0.05)。 结论窒息新生儿听觉刺激诱发相应皮层的神经活动时，显示局部脑血流量下降、氧合代谢降低，重度窒息儿更明显。