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991.
Investigation of rifampicin-induced hepatotoxicity in rat hepatocytes maintained in gel entrapment culture 总被引:1,自引:0,他引:1
Rifampicin-induced hepatotoxicity has been well recognized in animals and patients. However, it is undetectable in cultured
hepatocyte monolayers in vitro at the equivalent toxic concentration in vivo. This study investigated the rifampicin-induced
toxicity on rat hepatocytes in gel entrapment vs. in monolayer culture. Thiazolyl tetrazolium reduction and albumin secretion
were routinely detected to identify the toxic responses of rat hepatocytes to rifampicin, while reactive oxygen species (ROS)
accumulation and intracellular glutathione (GSH) content were assayed as biomarkers of oxidative stress. In addition, Nile
red staining and malondialdehyde (MDA) generation were, respectively, used as endpoints for lipid accumulation and peroxidation.
After treatment of hepatocytes for 96 h at a serum rifampicin concentration (12 μM), gel-entrapped rat hepatocytes showed
significant cellular damage indicated by alternations of all parameters indicated above, while hepatocyte monolayers did not
show severe responses. In contrast to a lack of protections by cytochrome P 450 inhibitors, the ROS scavenger (glycyrrhizic
acid) and thiol compounds (N-acetylcysteine and GSH) significantly reduced rifampicin toxicity in gel-entrapped hepatocytes. It appears that gel-entrapped
rat hepatocytes reflected significant hepatotoxicity of rifampicin in vivo, and this toxicity was most possibly associated
with oxidative stress and lipid accumulation. 相似文献
992.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the symptom of cognitive impairment. The deposition of amyloid β (Aβ) peptide is believed to be the primary cause to neuronal dystrophy and eventually dementia. Aβ is the proteolytic product from its precursor amyloid precursor protein (APP) by β- and γ- secretase. An optional cleavage by α-secretase happens inside the Aβ domain. ADAM17 is supposed to be the regulated α-secretase of APP. Enhanced activity of ADAM17 leads to the increasing secretion of neuroprotective soluble APP α fragment and reduction of Aβ generation, which may be benefit to the disease. ADAM17 is then considered the potential therapeutic target for AD. Microglia activation and neuroinflammation is another important event in AD pathogenesis. Interestingly, ADAM17 also participates in the cleavage of many other membrane-bound proteins, especially some inflammatory factors related to microglia activation. The facilitating role of ADAM17 in inflammation and further neuronal damage has also been illustrated. In results, the activation of ADAM17 as the solution to AD may be a tricky task. The comprehensive consideration and evaluation has to be carried out carefully before the final treatment. In the present review, the distinct role of ADAM17 in AD-related APP shedding and neuroinflammatory microglial activation will be carefully discussed. 相似文献
993.
卧床前后压力感受性反射机能变化的研究 总被引:2,自引:0,他引:2
许多数据表明长期失重以后立位耐力降低可能与压力感受性反射功能的改变有关。本文比较了两组被试者15天低动力卧床前后的立位耐力。以血压调节模型为基础分析了两种不同方式卧床前后单纯立位和下身负压加立位时压力感受性反射功能的改变,并用颈部加压及下身负压对中枢调节功能改变进行了观察。结果表明严格的头低位卧床后,立位耐力下降及压力感受性反射功能改变明显大于半日平卧半日倚坐者。而压力感受性反射功能的改变,特别是中枢神经系统调节功能的紊乱,是卧床后立位耐力降低的主要原因。从这种考虑为基础,作者提出了改变失重或模拟失重状态下的血液分布,调整对压力感受器的刺激,可能是预防心血管失调的有效方法。 相似文献
994.
995.
Du L Zhao G Lin Y Sui H Chan C Ma S He Y Jiang S Wu C Yuen KY Jin DY Zhou Y Zheng BJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(2):948-956
We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile. 相似文献
996.
D Su D You X Ren G Luo Y Mu G Yan Y Xue J Shen 《Biochemical and biophysical research communications》2001,285(3):702-707
The steady state kinetic study and some enzymic characterization of a selenium-containing scFv catalytic antibody (Se-scFv2F3) was carried out. A novel reaction formula of this abzyme-catalyzed reaction was proposed and a rate equation was gotten according to the formula. The constants in the equation were compared with Dalziel's parameters and the exact meanings of these constants were analyzed. The gotten kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed and compared with that of native glutathione peroxidase. 相似文献
997.
Tang C Inman MD van Rooijen N Yang P Shen H Matsumoto K O'Byrne PM 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):1471-1481
In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-gamma) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-gamma, but exacerbated when macrophages were depleted before IFN-gamma treatment. In addition, Th1-promoting activity of lung macrophages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-gamma, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses. 相似文献
998.
Comparative mapping of QTLs for agronomic traits of rice across environments by using a doubled-haploid population 总被引:11,自引:0,他引:11
Chaofu Lu Lishuuang Shen Ping He Ying Chen Lihuang Zhu Zhenbo Tan Yunbi Xu 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1997,94(1):145-150
We report here the RFLP mapping of quantitative trait loci (QTLs) which affect some important agronomic traits in cultivated
rice. An anther culture-derived doubled-haploid (DH) population was established from a cross between indica and japonica rice
varieties. A molecular linkage map comprising 137 markers was constructed based on this population which covered the rice
genome at intervals of 14.8 cM on average. The linkage map was used to locate QTLs for such important agronomic traits as
heading date, plant height, number of spikelets per panicle, number of grains per panicle, 1 000-grain weight and the percentage
of seed set, by interval mapping. Evidence of genotype-by-environment interaction was found by comparing QTL maps of the same
population grown in three diverse environments. A total of 22 QTLs for six agronomic traits was detected which were significant
in at least one environment, but only seven were significant in all three environments; seven were significant in two environments
and eight could only be detected in a single environment. However, QTLs-by-environment interaction was trait dependent. QTLs
for spikelets and grains per panicle were common across environments while traits like heading date and plant height were
more sensitive to environment.
Received: 22 February 1996 / Accepted: 10 May 1996 相似文献
999.
1000.
An ATP signalling pathway in plant cells: extracellular ATP triggers programmed cell death in Populus euphratica 总被引:2,自引:0,他引:2
Sun J Zhang CL Deng SR Lu CF Shen X Zhou XY Zheng XJ Hu ZM Chen SL 《Plant, cell & environment》2012,35(5):893-916
We elucidated the extracellular ATP (eATP) signalling cascade active in programmed cell death (PCD) using cell cultures of Populus euphratica. Millimolar amounts of eATP induced a dose‐ and time‐dependent reduction in viability, and the agonist‐treated cells displayed hallmark features of PCD. eATP caused an elevation of cytosolic Ca2+ levels, resulting in Ca2+ uptake by the mitochondria and subsequent H2O2 accumulation. P. euphratica exhibited an increased mitochondrial transmembrane potential, and cytochrome c was released without opening of the permeability transition pore over the period of ATP stimulation. Moreover, the eATP‐induced increase of intracellular ATP, essential for the activation of caspase‐like proteases and subsequent PCD, was found to be related to increased mitochondrial transmembrane potential. NO is implicated as a downstream component of the cytosolic Ca2+ concentration but plays a negligible role in eATP‐stimulated cell death. We speculate that ATP binds purinoceptors in the plasma membrane, leading to the induction of downstream intermediate signals, as the proposed sequence of events in PCD signalling was terminated by the animal P2 receptor antagonist suramin. 相似文献