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101.
M. Silvestri M. Bontempelli M. Giacomelli M. Malerba G. A. Rossi A. Di Stefano A. Rossi F. L. M. Ricciardolo 《Clinical and experimental allergy》2006,36(11):1373-1381
BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma. 相似文献
102.
目的探讨血清IL10、IL18在肝炎肝硬化的发病机制中的作用。方法62例肝炎肝硬化患者根据childpugh分级法分为3组:childpughA级组19例、childpughB级组23例和childpughC级组20例。采用ELISA法检测3组患者和20例健康献血员血清IL10、IL18的水平。结果childpughA、B、C级组血清IL18水平均明显高于对照组(P均<0.01),childpughA级组血清IL10水平略高于对照组,但无显著性差异(P>0.05);childpughB、C级组明显低于对照组(P<0.05);有腹水组、无腹水组血清IL18水平均明显高于对照组(P均<0.01),有腹水组血清IL10水平明显低于无腹水组、对照组(P<0.05,P<0.01);血清IL10水平与血清IL8水平呈负相关(r=-0.51,P<0.01);血清白蛋白水平与血清IL10水平呈正相关(r=0.566,P<0.01),与血清IL8水平呈负相关(r=-0.315,P<0.01);血清凝血酶原活动度与血清IL10水平呈正相关(r=0.506,P<0.01),与血清IL18水平呈负相关(r=-0.463,P<0.01);血清总胆红素水平与血清IL8水平呈正相关(r=0.677,P<0.01),与血清IL10水平呈负相关(r=-0.339,P<0.01)。结论IL10、IL18在肝炎肝硬化的发病机制中起一定的作用,其水平与肝损害程度密切相关。 相似文献
103.
T.H. Brun P. Lagier J.M. Dejode T. Attali F. Soula C. Granthil 《Annales fran?aises d'anesthèsie et de rèanimation》1990,9(6):553-556
A case is reported of fatal acute cerebral oedema occurring in a 15-year-old child suffering diabetic ketoacidosis. He had severe gastro-enteritis, with a weight lose of 8 kg over a period of 8 days (initial weight = 50 kg). He was admitted in a stupor with pH 7.15, 129 mmol.l-1 natraemia, and 31 mmol.l-1 blood glucose concentration. Blood osmolaity was calculated to be 310 mosmol.l-1. He was rehydrated with 416 ml.h-1 normal saline and 416 ml.h-1 of 1.4% sodium bicarbonate. At the same time a total dose of 75 i.u. of ordinary insulin was given. After 2 h, the patient's condition suddenly worsened with unreactive coma, bilateral fixed mydriasis, respiratory pauses, and impairment of haemodynamic state (heart rate 150 b.min-1, blood pressure 80/50 mmHg). The diagnosis of cerebral oedema with severe intracranial hypertension was confirmed by different investigations. Despite ventilatory support and continued intensive care, the patient died a few hours later. It is concluded that some degree of subclinical brain swelling could be common occurrence during diabetic ketoacidosis, present maybe even before the start of treatment. Such cases of cerebral oedema are often reported, but the pathophysiological mechanisms remain unclear. However, unlike this case, rehydration must be moderate (less than 41.m-2.day-1), especially in case of hyponatraemia. Insulin and sodium bicarbonate must be used with care. Early rigorous clinical and biological monitoring is essential. Treatment should aim at a progressive correction of the metabolic disturbances. 相似文献
104.
Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the
(NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A1 receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA1 area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects. 相似文献
105.
Trang T. Duong Joanne St. Louis Joseph J. Gilbert Fred D. Finkelman Gill H. Strejan 《Journal of neuroimmunology》1992,36(2-3)
SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE. 相似文献
106.
W. R. Coward H. Sagara S. J. Wilson S. T. Holgate M. K. Church 《Clinical and experimental allergy》2004,34(7):1071-1078
BACKGROUND: Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen-induced activation of eosinophil NF-kappaB and generation of granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8. METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF-kappaB activation by 10 microg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF-kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot. Cytokine production was assessed both by immuno-staining of eosinophils and by assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral blood eosinophils from atopic, but not non-atopic, donors induced activation of NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha. The activation of authentic NF-kappaB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB. Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF-kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo. 相似文献
107.
108.
Deep brain stimulation, DBS, is an accepted technique for the treatment of Parkinson's disease. DBS affects the electrical functions of neurons, but exactly how it alters those functions is not clearly explained. An electrical model is determined to simulate treatment with DBS of the sub thalamic nucleus. This model shows the difference in electrical fields between the inside and the outside the neurons. The generated electrical field near the electrodes is high enough to perform an electropermeabilization of the cell membranes, which most likely blockade normal nerve pulses or reduce the nerve impulse speed. Further away from the electrodes activation of large axons is performed. 相似文献
109.
肿瘤微环境对树突细胞功能状态的影响 总被引:2,自引:0,他引:2
目的:探讨肿瘤细胞分泌的可溶性细胞因子营造的微环境对树突细胞(DCs,dendritic cells)的分化发育的影响,以进一步揭示肿瘤的免疫逃逸机制。方法:用免疫磁珠从人外周血分离CD14^ 单核细胞,加入粒细胞巨噬细胞集落刺激因子(GM-CSF)、白细胞介素4(IL-4)和人白血病细胞Jurkat培养上清液体外培养DCs,以正常培养诱导的DCs作为对照,采用傅立叶变换红外光谱(FTIR)技术分析人白血病细胞培养上清液对DCs分化发育的影响。结果:正常培养DCs与肿瘤上清液培养的DCs相比,在细胞内蛋白质和核酸的相对含量和细胞内消耗葡萄糖重新合成磷脂的量方面差异无显著性,但是,在细胞的转录状态方面差异有显著性。结论:肿瘤细胞上清液培养液所营造的微环境细胞转录水平上对DCs的功能状态有明显的抑制作用。 相似文献
110.
The aim of this study was to identify the factors associated with better or worse quality of life in a sample of people with Menière's disease drawn from a UK self‐help group (the Menière's Society) and to assess the forms of support on which the respondents could draw. A postal survey was sent to 1000 randomly selected group members, containing validated questionnaires assessing: (1) quality of life (the Short Form 36 (SF‐36)); (2) factors that might predict quality of life; and (3) usage of resources provided to members by the Menière's Society. A total of 509 members completed the main survey, and 370 the second part of the survey. Factors associated with a less good quality of life included more severe vertigo, pressure in the ear, hearing loss and tinnitus, being younger, being female, living alone, having a lower occupational status and believing that the attitude of the consultant is unhelpful. Levels of vertigo severity in this sample were similar to those found in hospital samples, but it is possible that these respondents may differ in other respects from patients who do not join a self‐help group. 相似文献