Glutamate is a major excitatory neurotransmitter in the central nervous system(CNS)and plays an important role in neuronal damage induced by cerebral ischemia. Several mechanisms contribute to modulation of glutamate release during cerebral ischemia, such as vesicular release dependent on calcium, release by reversed operation of glutamate transporters, release through swelling-activated anion channel and receptor-modulating release, etc. This review addresses the mechanisms of glutamate release during cerebral ischemia.

Aim To study the involvements of nuclear factor of activated T-cells (NFATc) and NFκB in calcineurin-mediated ischemic brain damage in vivo. Methods The rat transient forebrain ischemia conducted through 15 min ischemia followed by 8, 24, and 72 h reperfusion was induced using the fourvessel method. The rats were divided randomly into five groups; sham control group, ischemia/reperfusion (I/R) group, CsA treated groups (for 8, 24, and 72 h reperfusion). Western blotting was performed to detect changes of FasL, NFATc, I-κB-α, and phospho-I-κB-α protein expression, and gel shift assays for NFAT FasL-DNA binding activities. Results Western blotting showed that the expressions of both FasL and NFATc protein were significantly increased in the hippocanpus of rat subjected to transient forebrain ischemia in comparison with those of the sham control group, which were markedly reduced by CsA. The I-κB-α protein showed no changes in all groups, and phospho-I-κB-α protein was not observed in this study. Proximal and distal FasL promoter NFAT sites bind NFAT proteins from the hippocampal neurons subjected to transient forebrain ischemia, and DNA-binding activities increased significantly compared with those of the sham control group. CsA markedly inhibited these changes. Conclusion NFATc may be involved in calcineurin-mediated ischemic brain damage and transcription factor NF-κB may not be involved.

AIM To study the effect and mechanism of valdecoxib, a selective COX 2 inhibitor, on human gastric cancer BGC 823 cells. METHODS MTT assay and flow cytometry were used to observe the effect of valdecoxib on proliferation, apoptosis and the cell cycle distribution of BGC 823 cells. Laser confocal microscopy, transmission electron microscope and DNA fragmentation assay were further used to detect the apoptosis. The content of LDH was examined using LDH kit. RESULTS Valdecoxib in 25～400 ?mol?L -1 significantly inhibited the proliferation of BGC 823 cell in a time and dose dependent fashion, the inhibition rate of proliferation was 24 0%～92 0% after 72 h, and the rate of apoptosis was increased from (2 6?0 7)% to (7 6?1 5) %～(16 5?1 5)%. 100～400 ?mol?L -1 valdecoxib also decreased the proliferation index and the proportion of cells in the S phase, increased the proportion of cells in the G 0/G 1 phase, but had no effect on the proportion of cell in the G 2/M phase. CONCLUSION Valdecoxib inhibits human gastric cancer BGC 823 cells growth by inducing apoptosis and cell cycle arrest. The growth inhibitory effect of 400 ?mol?L -1 valdecoxib is also associated with cell necrosis.

Aim To study the effects of dipfluzine (Dip) on cell apoptosis after focal cerebral ischemia-reperfusion injury in rats. Methods Endothelin-1 induced focal cerebral ischemia-reperfusion model in rat was used in experiment. The cell apoptosis, the expressions of Bcl-2 and Bax proteins were observed by flow cytometric analysis. Results The tissues from the solvent group showed remarkably high apoptotic percentages with(9.34?1.22)% in cortex and(10.58?1.44)% in striatum, respectively, in contrast with(1.26?0.15)% in cortex and(2.50?0.35)% in striatum in sham group. Dipfluzine could decrease the cell apoptosis in cortex and striatum and showed a close correlation with the dose increment, which were (7.92?0.76)% in 10mg?kg -1 group, (6.78?0.77)% in 20 mg?kg -1 group, and (6.00?0.71)% in 40 mg?kg -1 group in cortex (r=0.9559, P0.05). The determination of Bcl-2 and Bax by flow cytometric analysis indicated that sham group showed high expression of Bcl-2 both in cortex and striatum and the ratio of Bcl-2 and Bax were the highest,they were 1.30?0.08 in cortex and 1.64?0.10 in striatum, respectively. The expression of Bax in solvent group was increased and the the ratio of Bcl-2 and Bax were 1.03?0.12 in cortex and 1.00?0.04 in striatum, significantly lower than those in sham group (P

AIM To establish an Endothelin 1 induced focal cerebral ischemia and reperfusion model. METHODS Endothelin 1(ET 1), a potent vasoconstrictor, was injected near the middle cerebral artery to induce reduction in cerebral blood flow and ischemic neuronal damage. The changes of cerebral blood flow in striatum were characterised using hydrogen clearance technique. The neurologic scores were performed and the infarct volume was identified by TTC staining at 6 h and 24 h after ET 1 application, respectively. RESULTS ET 1 induced a dose dependent reduction of cerebral blood flow in striatum and the CBF at 10 min after ET 1 injection were the lowerest. CBF at 10 min post injection was (27 1?2 9)% in group 300 pmol, (12 7?2 1) % in group 360 pmol, (11 9?1 8)% in group 400 pmol and (9 5?1 6)% in group 500 pmol , respectively. Neurologic score showed that ET 1 could induce variable grade neurologic deficit. The infarct volume were increased with the increment of ET 1 concentration and showed a close correlation, which were (3 9?0 3)% in group 300 pmol, (7 4?0 5)% in group 360 pmol, (11 3?1 3)% in group 400 pmol, and (16 2?1 8)% in group 500 pmol respectively, r =0 992 6 ( P

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode's solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 μmol·L-1), but remained no change in the presence of Str (1 and 100 nmol·L-1). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol·L-1), but had no obvious effects on the action of Str (10 μmol·L-1). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 μmol·L-1) or the removal of Ca2+ from Tyrode's solution. In Na+, K+-free Tyrode's solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 μmol·L-1) was attenuated, while remained no change to Str (1 and 100 nmol·L-1). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+-free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+-ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.

Objective To investigate the status of blood donation in Shanghai streets,understanding the motivation of the donors for blood donation and how many times they had donate their blood.Here,we intend to improve work efficiency in order to better serve the blood donators and to provide a theoretical basis.Methods To gain insight into the understanding and attitude of citizens for blood donation,we analyzed the volunteer blood donors in 387 vehicles and 436 outdoor pre mobilization object by six months,questionnaire in blood collection vehicle or at scene etc.Results The survey specifically reflected the understanding,attitude and motivation of citizens and foreign workers for blood donation in Shanghai.Conclusion There existed many problems such as wrong recognition,diversified motivation among many citizens for blood donation.More publicity and education for the knowledge of blood donation are needed and it plays significant and longlasting role for blood donation.

A new instrument, furnished with hydrogen clearance technique for measuring local blood-flow, was designed by use of new electronic components and a microcontroller. The corresponding program was developed. The curve of hydrogen clearance was sampled automatically by microcomputer, fitted into an exponential function by least square method, and then the local blood-flow was calculated. The cerebral blood-flow in the rat's striatum had been measured using the system. The fitted curve corresponds with the curve of hydrogen clearance and the obtained parameter was correct. The design of the instrument was reasonable. It can work reliably and stably. The calculated results are more accurate and they can be acquired more quickly, because the curve of hydrogen clearance is automatically sampled and analyzed by the microcomputer.
Animals ; Cerebrovascular Circulation ; physiology ; Equipment Design ; Hydrogen ; analysis ; pharmacokinetics ; Male ; Microcomputers ; Monitoring, Physiologic ; instrumentation ; Rats ; Rats, Wistar ; Regional Blood Flow ; physiology ; Rheology ; instrumentation ; Signal Processing, Computer-Assisted

ObjectiveTo investigate the principle and scientific connotation of Euodiae Fructus（EF） processed with Glycyrrhizae Radix et Rhizoma（Gly） by comparing the effects of unprocessed products of EF（UEF） and processed products of EF with the different proportions of Gly（GEFs） at toxic doses on oxidative stress and autophagy in the liver of mice. MethodSeventy mice were randomly divided into 7 groups， namely the control group， the UEF group， the group of the processed products of EF without Gly（PEF） and 4 groups of GEFs（the mass ratios of EF to Gly were 100∶3， 100∶6， 100∶12 and 100∶24， respectively， hereinafter referred to as the processed products of EF with the mass ratios of 100∶3， 100∶6， 100∶12 and 100∶24 of Gly）. The mice were given purified water， the decoction of UEF， PEF and GEFs by gavage at a dose of 30 g·kg^-1. PEF and GEFs were prepared according to the method under EF in the 2020 edition of Chinese Pharmacopoeia. Levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were determined by ultraviolet-visible spectrophotometry， hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of liver tissue， the level of reactive oxygen species（ROS） was detected by fluorescence method， the mRNA expression of heme oxygenase-1（HO-1）， quinone oxidoreductase-1（NQO1）， glutathione-S-transferase 1（GSTA1）， Kelch-like epichlorohydrin-associated protein 1（Keap1） and p62 were measured by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， western blot was used to detect the protein expression of phosphorylated mammal target of rapamycin（p-mTOR）， phosphorylated ribosomal p70 S6 protein kinase（p-p70S6K）， p62， microtubule-associated protein 1 light chain 3Ⅰ（LC3Ⅰ） and LC3Ⅱ. ResultCompared with the control group， after 7 d of administration， the increase in body mass of mice in the UEF group began to slow down and the difference gradually increased， and the liver body index significantly increased（P<0.01）， pathomorphological observation showed that the structure of hepatic lobules was disordered， and local hepatic sinuses were narrowed or disappeared， and there were inflammatory infiltration and local bleeding， the levels of ALT and AST in serum and ROS in liver tissue were significantly increased（P<0.01）， and the expressions of Keap1， HO-1， NQO1， GSTA1， p62 mRNA and p-mTOR， p-p70S6K， p62 protein in liver tissue were significantly decreased（P<0.01）， and LC3Ⅱ/LC3Ⅰ was significantly increased（P<0.01）. Compared with the UEF group， the body mass of mice increased， and the liver body index， the levels of ALT and AST in serum， and the level of ROS in liver tissue all decreased in the groups of PEF and GEFs. Among these groups， only the liver lobules in GEF（100∶6） group were intact， and the size of liver sinuses was close to that in the control group. The mRNA expressions of Keap1， HO-1， NQO1， GSTA1 and p62 in liver tissue showed an overall upward trend in the groups of PEF and GEFs. Among these groups， only the ones of the above mRNA in the GEF（100∶6） group had a significant increase（P<0.05， P<0.01）. The protein expressions of p-mTOR， p-p70S6K， p62 and LC3Ⅱ/LC3Ⅰ had a callback in the groups of PEF and GEFs， of which the protein expressions of p-mTOR， p-p70S6K and LC3Ⅱ/LC3Ⅰ in the GEF（100∶6） group and the expression of p62 protein in the GEF（100∶24） group had the largest callback. Except for p-mTOR protein， other protein expressions were statistically significant（P<0.05， P<0.01）. ConclusionThe hepatotoxicity of EF is closely related to its ability to induce oxidative stress， which leads to pathological autophagy and hepatocyte damage. This ability can be reduced by the processing with different proportions of Gly， especially the ratio of 100∶6.