Inflammatory biomarkers in blood of patients with acute brain ischemia

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.     

Fever and feeding in the rat: Actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1β (MIP-1β)

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1β, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (T_b) of MIP-1β with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor T_b continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 μl of pyrogen-free artificial CSF, recombinant murine MIP-1β, or recombinant human IL-6. MIP-1β in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in T_b of 2.4 ± 0.21°C reached by 3.7 ± 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in T_b of 1.2 ± 0.25°C, 1.8 ± 0.15°C, and 2.1 ± 0.22°C and duration of 6.2 ± 1.28 hr, 6.7 ± 0.49 hr, and 6.8 ± 0.65 hr when given in doses of 25, 50, and 100 ng, respectively. These results show that MIP-1β and the highest dose of IL-6 induce a fever of comparable intensity, but MIP-1β exerts its action in a much lower concentration. Thus, the de novo synthesis and subsequent action of the MIP-1 family of cytokines on neurons of the AH/POA in response to a pyrogen challenge apparently play a functional role in the pathogenesis of fever. Further, the endogenous activity of IL-6 in the hypothalamus which is enhanced in response to a lipopolysaccharide also may reflect its essential part in the acute phase response to a bacterial challenge. Copyright © 1994 Wiley-Liss, Inc.     

Unilateral lesion of the nigrostriatal pathway decreases the firing rate and alters the firing pattern of globus pallidus neurons in the rat

Activities of spontaneously firing neurons in the globus pallidus of intact rats and rats that survived unilateral lesions of the nigrostriatal pathway for 3 days, 1 week, or 6-11 weeks were compared. No significant differences in neuronal firing rate, firing pattern, and number of cells per pass were observed between chloral hydrate-anesthetized control and lesioned animals. However, in locally anesthetized animals, pallidal cells fired significantly faster than in chloral hydrate-anesthetized animals, and the lesion caused a decrease in the firing rates of pallidal cells 1 week and 6-9 weeks postlesion. In addition, significant differences in the firing pattern of pallidal cells, as determined by the ratio of the mean to median interspike intervals, were seen between locally anesthetized controls and animals surviving 3 days, 1 week, and 6-9 weeks postlesion. This altered firing pattern tended to return to normal with time. The number of cells per pass was not significantly altered by the lesion. Data from this study suggest that, in locally anesthetized animals, the removal of the tonic dopaminergic input to the basal ganglia causes pallidal cells to decrease their firing rates in a time-dependent fashion and causes reversable firing pattern changes. This suggests that tonically active dopamine neurons, probably acting through the striatopallidal pathway, regulate the firing rate and mechanisms controlling the temporal ordering of spontaneous discharges of globus pallidus neurons.     

乳腺癌组织中STAT3激活的意义

目的:分析STAT3在乳腺癌及癌旁乳腺组织中的激活水平与乳腺癌临床分期的关系,探讨STAT3在乳腺癌发病机制中的作用.方法:乳腺癌手术标本36例,免疫组化SP法检测STAT3蛋白在乳腺癌组织中的表达;凝胶迁移电泳率实验测定STAT3在乳腺癌及癌旁乳腺组织中的激活水平.结果:在临床ⅡA,ⅡB和ⅢA期乳腺癌组织中STAT3激活水平均明显高于同期癌旁乳腺组织(P均＜0.01),ⅡA,ⅡB和ⅢA期乳腺癌组织中STAT3激活水平无显著差异(P＞0.05);STAT3蛋白主要表达于细胞质和细胞核.结论:STAT3可能在乳腺癌的发生发展中有重要的作用;抑制STAT3的激活可能成为治疗乳腺癌的一种新的途径.     

Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

原发性胆囊癌CD44v6和bcl-2的表达及其与临床病理的关系

目的　探讨CD44v6和bcl 2蛋白在原发性胆囊癌组织中的表达及其与癌组织类型、病理分级和转移状况的关系 ,以及CD44v6表达与bcl 2表达的相关性。方法　应用免疫组织化学方法检测 50例原发性胆囊癌、2 0例胆囊腺瘤和 1 0例慢性胆囊炎组织中CD44v6和bcl 2蛋白的表达。结果　胆囊癌组织中CD44v6和bcl 2表达阳性率分别为82 .0 %和 60 .0 % ,均明显高于胆囊腺瘤 (分别为 45 .0 %和 30 .0 % ,P<0 .0 5) ,并随着胆囊癌细胞分化程度的减低、病理分级的增高和转移而明显增高 (P<0 .0 5)。同时 ,CD44v6的表达与bcl 2表达呈正相关 (r =0 .36 ,P<0 .0 5)。结论　CD44v6和bcl 2均是胆囊癌高度恶性和预后不良的重要指标。胆囊癌CD44v6表达与bcl 2蛋白表达可能具有相互协同作用。     

恙虫病东方体在无生命培养基内生长的研究

目的　恙虫病东方体 (Orientiatsutsugamushi;Ot)被认为属专性细胞内寄生。特别是制备大量抗原培养难的问题 ,是近一个世纪以来人们渴望解决的难题。为证实是否能在无生命培养基生长。方法　用Vero -E6个单层组织细胞培养OtJL - 90株与标准Gilliam株 ,在合适时取该培养物接种于Ⅲ号无生命固体培养基培养 ,置 36℃ (± 1℃ )培养 18- 2 4h。结果　可见生长一群无色透明或半透明光滑、湿润、圆形或枫叶样小菌落 ,并产生一种难闻的臭味。两种方法培养物分别做了生物学性状鉴定、形态染色、小白鼠致病力、血清学特异性间接免疫荧光检测。各株Ot经两种培养获得培养物特性基本一致。结论　Ot能在细胞内生长也能在无生命培养基内生长 ,解决了Ot大量抗原培养难的困扰。