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11.
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Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases 总被引:1,自引:0,他引:1
Microglia are the resident immune cells of the CNS, which are important for preserving neural tissue functions, but may also contribute to neurodegeneration. Activation of these cells in infection, inflammation, or trauma leads to the release of various toxic molecules, including reactive oxygen species (ROS) and the excitatory amino acid glutamate. In this study, we used an electrophysiologic approach and a d‐[ 3 H] aspartate (glutamate) release assay to explore the ROS‐dependent regulation of glutamate‐permeable volume‐regulated anion channels (VRACs). Exposure of rat microglia to hypo‐osmotic media stimulated Cl? currents and d ‐[3H]aspartate release, both of which were inhibited by the selective VRAC blocker, DCPIB. Exogenously applied H2O2 potently increased swelling‐activated glutamate release. Stimulation of microglia with zymosan triggered production of endogenous ROS and strongly enhanced glutamate release via VRAC in swollen cells. The effects of zymosan were attenuated by the ROS scavenger, MnTMPyP, and by two inhibitors of NADPH oxidase (NOX), diphenyliodonium and thioridazine. However, zymosan‐stimulated glutamate release was insensitive to other NOX blockers, apocynin and HEBSF. This pharmacologic profile pointed to the potential involvement of apocynin‐insensitive NOX4. Using RT‐PCR we confirmed that NOX4 is expressed in rat microglial cells along with NOX1 and NOX2. To check for potential involvement of phagocytic NOX2, we stimulated this isoform using protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate or inhibited it with the broad spectrum PKC blocker, Gö6983. Both agents potently modulated endogenous ROS production by NOX2 but not VRAC activity. Taken together, these data suggest that the anion channel VRAC may contribute to microglial glutamate release and that its activity is regulated by endogenous ROS originating from NOX4. 相似文献
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Using equilibrium dialysis and sedimentation velocity analysis, we have characterized the binding of the anti-tumor drug daunomycin to chicken erythrocyte chromatin before and after depletion of linker histones and to its constitutive DNA under several ionic strengths (5, 25, and 75 mM NaCl). The equilibrium dialysis experiments reveal that the drug binds cooperatively to both the chromatin fractions and to the DNA counterpart within the range of ionic strength used in this study. A significant decrease in the binding affinity was observed at 75 mM NaCl. At any given salt concentration, daunomycin exhibits higher binding affinity for DNA than for linker histone-depleted chromatin or chromatin (in decreasing order). Binding of daunomycin to DNA does not significantly affect the sedimentation coefficient of the molecule. This is in contrast to binding to chromatin and to its linker histone-depleted counterpart. In these instances, preferential binding of the drug to the linker DNA regions induces an unfolding of the chromatin fiber that is followed by aggregation, presumably because of histone-DNA interfiber interactions. 相似文献
15.
Guobao Zhang Pingda Ren Nathanael S. Gray Taebo Sim Xia Wang Yi Liu Jianwei Che Weitong Dong Shin-Shay Tian Mark L. Sandberg Tracy A. Spalding Russell Romeo Maya Iskandar Zhiliang Wang H. Martin Seidel Donald S. Karanewsky Yun He 《Bioorganic & medicinal chemistry letters》2009,19(23):6691-6695
A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs. 相似文献
16.
Cui-Ping Cao Oliver Gailing Iskandar Z. Siregar Ulfah J. Siregar Reiner Finkeldey 《Tree Genetics & Genomes》2009,5(3):407-420
Shorea is the largest and most important genus of the Dipterocarpaceae. The genetic diversity and structure of nine Shorea species from two different locations, namely Nanjak Makmur in Sumatra and Sumalindo in Borneo, were evaluated using amplified
fragment length polymorphism (AFLP) markers. A total of 274 trees were investigated at 85 polymorphic AFLP loci. Levels of
genetic diversity of these species ranged from = 0.100 for S. acuminata to = 0.165 for S. blumutensis. The population of rare species S. blumutensis possessed the highest genetic diversity suggesting that geographically restricted species can have levels of genetic variation
comparable to closely related widespread common congeners. Analyses of molecular variance revealed that the genetic variation
was mainly found among species in both locations (57.7% in Sumatra; 56.3% in Borneo). The unweighted pairgroup method using
arithmetic averages dendrogram of all samples revealed an almost complete separation of species. Thus, AFLP markers proved
appropriate for phylogenetic studies of Shorea species. Specific markers have been detected showing high-frequency differences among species and between regions within
species. Sequence information of these markers can be used to develop specific polymerase chain reaction markers for wood
identification. The possibility of interspecific hybridization was discussed. 相似文献
17.
There is a prohibition on the use of modern external inputs, such as chemical fertilizers, in Baduy swidden farming. Ordinarily, the consequence of this in a situation of acute forest pressure would be a decrease in fallow times, and an inevitable depletion of soil fertility. The Baduy (particularly Outer Baduy) have several ways of alleviating this problem, one of which is the introduction of Paraserianthes (Albizia) falcataria. By alternating this commercially valuable perennial leguminous tree with rice, soil fertility is maintained and the socio-economic position of the Baduy improved. As a result, swidden farming, which is considered by the Baduy to be central to their cultural identity, continues to be viable, despite increasing population density and the continuing depletion of mature forest. 相似文献
18.
Ranita Hisham Su May Liew Chirk Jenn Ng Kamaliah Mohd Nor Iskandar Firzada Osman Gah Juan Ho Nurazira Hamzah Paul Glasziou 《PloS one》2016,11(3)
Background
Evidence-based medicine is the integration of individual clinical expertise, best external evidence and patient values which was introduced more than two decades ago. Yet, primary care physicians in Malaysia face unique barriers in accessing scientific literature and applying it to their clinical practice.Aim
This study aimed to explore the views and experiences of rural doctors’ about evidence-based medicine in their daily clinical practice in a rural primary care setting.Methods
Qualitative methodology was used. The interviews were conducted in June 2013 in two rural health clinics in Malaysia. The participants were recruited using purposive sampling. Four focus group discussions with 15 medical officers and three individual in-depth interviews with family medicine specialists were carried out. All interviews were conducted using a topic guide and were audio-recorded, transcribed verbatim, checked and analyzed using a thematic approach.Results
Key themes identified were: (1) doctors viewed evidence-based medicine mainly as statistics, research and guidelines, (2) reactions to evidence-based medicine were largely negative, (3) doctors relied on specialists, peers, guidelines and non-evidence based internet sources for information, (4) information sources were accessed using novel methods such as mobile applications and (5) there are several barriers to evidence-based practice, including doctor-, evidence-based medicine-, patient- and system-related factors. These included inadequacies in knowledge, attitude, management support, time and access to evidence-based information sources. Participants recommended the use of online services to support evidence-based practice in the rural settings.Conclusion
The level of evidence-based practice is low in the rural setting due to poor awareness, knowledge, attitude and resources. Doctors use non-evidence based sources and access them through new methods such as messaging applications. Further research is recommended to develop and evaluate interventions to overcome the identified barriers. 相似文献19.
Sandia B. Pezerico Helio Langoni Aristeu V. Da Silva Rodrigo C. Da Silva 《Experimental parasitology》2009,123(2):168-177
Toxoplasma gondii infection is common worldwide and highly important to pregnant women as it can be transmitted to the fetus via the placenta. This study aimed at evaluating the prevention of placental transmission in two different strains after chronic infection with each one of the strains. A BALB/c mice model was inoculated 30 days before breeding (immunization) and re-infected 12 and 15 days after pregnancy (challenge). Seven experimental groups were assayed: G1: ME49-immunization (type II), M7741-challenge (type III); G2: M7741-immunization, ME49-challenge; G3, ME49-immunization; G4: M7741-immunization; G5: ME49-challenge; G6: M7741-challenge; G7: saline solution inoculation. Serology, mouse bioassay, PCR and RLFP of the uterus, placenta and fetus were performed to determine the congenital transmission of the strains challenged after chronic infection. IgG T. gondii antibodies were detected in G1, G2, G3 and G4, but not in G5, G6 and G7. All animals of G5 and G6 were IgM-positive. Congenital infection was not detected by bioassay and PCR. Nonetheless, placentas from G3 and G4 resulted positive but no corresponding fetal infection was detected. G1 and G2 did not show the genotype of the strain challenged during pregnancy, only those of chronic infection. Thus, the chronically infected BALB/c mice showed no re-infection after inoculation with another strain during pregnancy. Further studies with different parasite loads and different mice lineages are needed. 相似文献
20.
Six species of the genus Thermocyclops have hitherto been known from Chinese freshwaters. A new species is here recorded from a sample collected from an eutrophic pool in central China. It is described and compared using classical morphology and mapping of its pore signature. Thermocyclops dumonti differs from T. kawamurai by absence of ornamentation on prominences of intercoxal plates of P1‐P3, by relative length of apical spines of Enp3P4 and caudal ramus. It differs from T. dybowskii by ornamentation of P4 intercoxal plate, relative length of Enp3P4 and caudal ramus, by shape of Tmi. As in other species of Thermocyclops, the perforations are bilaterally symmetrical and, species‐specific patterns occur on the cephalosome, metasome, and urosome. Conserved patterns are found elsewhere on the rostrum, cephalosome, metasome, and furcal branches. Based on pore pattern, Thermocyclops dumonti is separated from two close relatives, T. schmeili and T. dybowskii. 相似文献