The clinical features and plasma malondialdehyde(MDA) contents were studied in 91 patients with acute cerebral vascular disease (ACVD). The cerebrospinal fluid (CSF) MDA contents were also measured in 51 of them. The MDA contents increased significantly more than that of the control group. The difference of CSE MDA between the disease group and control was more significantly than that of plasma. It may be due to the fact that the CSE MDA level reflects the severity of lipid peroxidative reaction (LPR) in brain directly, whereas plasma MDA level reflects the severity of systemic LPR. The dynamic change of plasma MDA is closely related to the outcome of the disease. The plasma MDA decreases in ameliorated patients, but increases in the aggravated. The measurement of palsma MDA may be used as an indicator to predict the prognosis of ACVD.

The selective vulnerability of brain tissues after 30 minutes of complete ischemia was observed 5, 15, and 30 minutes after ischemia and 15, 60, and 180 minutes after reperfusion in rats under optical and electron microscopies. It was found that the cerebral cortex especially the third and fifth lamina, the H1 segment of the hippocampus, and the Purkinje cells of the cerebellum were most liable to be damaged after ischemia. After reperfusion, the alterations of membrane system, nuclei and organelles were significant. The membraneous structures which contained a large amount of lipids were more severely damaged. At the same time cerebral edema was found, the severity of which was correlated with the intensity of histopathological and ultrastructural changes of the brain and the degree of blood brain barrier disruption.The findings suggest that oxygen free radicals and lipid peroxides may play an important role in the development of the damages in the brain mentioned above after reperfusion.

The dynamic changes of the contents of polyamines and excitatory amino acid in the hippocampus during cerebral ischemia and reperfusion were observed in rats.It was found that the content of putrescine was increased and the release of excitatory amino acid elevated during reperfusion,and the increase of putrescine could be stopped when the antagonist of NM-DA receptor of excitatory amino acid,that is,MK-801,was administered.These facts suggest that the metabolic disturbance of polyamines in closely related to the release of excitatory amino acid and modulated by NMDA receptors.The combination of polyamines with excitatory amino acid may play an important role in the ischemic damage of the brain.

Objective To explore the possible mechanism by which protein kinase C (PKC) involves in the neuronal apoptosis induced by cerebral ischemia/reperfusion Methods After the model of ischemia/reperfusion was established in male Wistar rats, PKC activity, FOS protein expression and neuronal apoptosis in their brains were observed The effect of PKC inhibitor, Dengzhanghua, on above indexes were studied at the same time Results Cerebral ischemia/reperfusion resulted in transloactional activation of PKC, accompanied with the increase of FOS expression and neuronal apoptosis Dengzhanghua prevented against the above changes Conclusion Activated PKC is involved in ischemia/reperfusion induced neuronal apoptosis by regulating FOS expression

BACKGROUND: Repetitive brief and non-lethal cerebral ischemia can produce cumulative neuronal damage and vascular dementia; however, precisely injured patterns and mechanisms are still unclear. Thalamus is an important structure of learning and memory; meanwhile, it is also one of the selectively vulnerable regions of cerebral ischemia.However, there are a few reports about neuronal damage induced by repetitive cerebral ischemia.OBJECTIVE: To investigate the pathological damage and mechanism of neurons induced by repetitive cerebral ischemia in thalamus.DESIGN: Randomized controlled experimental study.SETTING: Department of Neurology, General Hospital of Chengdu Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out at the Animal Central Laboratory of the Third Military Medical University of Chinese PLA from March to December 1999. A total of 72 healthy male Wistar rats were randomly divided into sham operation group, single cerebral ischemic group,repetitive cerebral ischemic group, MK-801 treatment group and saline group.METHODS: Transient global cerebral ischemia models of rats were established with modified Pulsinelli-4 vessel occluing method for single 15-minute ischemia and repetitive three 5-minute ischemia at hourly intervals,followed by 5 hours, 2 days and 4 days of survival. Rats in sham operation group were not treated with burning vertebral artery and clipping common carotid artery. 45Ca autoradiography and light microscopy were used to determine the calcium accumulation and neuronal pathological changes of thalamus following repetitive cerebral ischemia as compared with single cerebral ischemia. The effects of MK-801, a N-methyl-D-aspartate (NMDA)receptor antagonist, were also examined.MAIN OUTCOME MEASURES: Distribution and degree of calcium accumulation and neuronal damage in the thalamus of rats in each group.RESULTS: Sham-operated rats revealed no abnormal calcium accumulation and neuronal damage in the thalamus. At 5 hours following ischemia,slightly abnormal calcium accumulation was found in the partial thalamus of the repeated ischemic group, and the neuronal damage was also relatively severer than that in the single ischemic group (0.98±0.19, 0.60±0.14, P＞ 0.05). At 2 days after ischemia, obviously abnormal calcium accumula tion and neuronal damage were shown in thalamus, and the degree of calcium accumulation and score of neuronal damage in repeated ischemic group were significantly severer than that in single ischemic group (1.62±0.31, 0.88±0.21, P ＜ 0.01). At 4 days, the thalamus calcium accumulation and neuronal damage were further increased, and also that in repeated ischemic group was significantly severer than that in single ischemic group (1.80±0.21, 1.02±0.23, P ＜ 0.01), especially marked calcium accumulation and cumulative damage were shown in the ventral thalamus. MK-801 significantly relieved the abnormal calcium accumulation and neuronal damage in the thalamus in repeated ischemic group, showing significant protection of thalamus neurons as compared with that in saline-treated group (0.20±0.12, 1.80±0.15, P ＜ 0.01).CONCLUSION: Repetitive non-lethal cerebral ischemia results in an intense cumulative damage in the ventral thalamus, and the excitatory amino acid and Ca2+ may play a major role in it.

AIM:To study pharmacokinetic of Pueraria Flavonid Nasal Drop in rabbits through nasal administration in comparison with oral administration. METHODS:Ten New Zealand rabbits were divided into two groups randomly and administrated nasally and orally (106.4 mg/kg of pueraria flavonid). HPLC was adopted to detect pueraria flavonoid content and DAS 2.0 was used to calculate bioavailability. RESULTS:The main pharmacokinetic parameters of nasal and oral administrations were AUC (0-∞)1 =(30.55?4.93)mg/(L?h),T max1 =(0.90?0.14)h,C max1 =(11.27?1.66)mg/L;AUC (0-∞)2 =(6.90?2.76)mg/(L?h),T max2 =(0.63?0.34)h,C max2 =(1.68?0.84)mg/L. Relative bioavailability of nasal delivery was 442.8%. CONCLUSION:Pueraria Flavonoid Nasal Drop is well absorbed in rabbits and has high bioavailability.

Objective To investigate the effects of skin/muscle incision and retraction(SMIR)on mechanical paw withdrawal threshold and the ability of spatial learning and memory in immature rats after adulthood. Methods 27 male SD rats aged 3 weeks and weighing 60 ~ 80 g were randomly divided into 3 groups(n = 9):control group(group C),sham operation group(group Sham)and skin/muscle incision and retraction group (group SMIR). Group SMIR received operation for skin/muscle incision and retraction. Sham group received skin/muscle incision but no retraction.No surgery was operated on C group. Pain behavior was assessed by mechanical paw withdrawal threshold(MWT)to von Frey filament stimulation before and 1,3,7,12,22 and 32 days after operation.The effects of spatial learning and memory function were assessed by Morris water-maze test at 33 days after operation. Results Mechanical paw withdrawal threshold of group SMIR decreased 1 day after operation (P<0.05)and showed no significant difference before and 3,7,12,22,32 days after operation in 3 groups(P >0.05). In Morris water-maze test,compared with Sham and C group,the average escape latency in SMIR was sig-nificantly longer in the water maze navigation experiment(P < 0.01);the ratios of time and path in the quadrant of the platform were obviously lower in SMIR(P < 0.01). There was no statistical difference between sham and C group(P>0.05).Conclusion SMIR did not cause chronic pain but may cause a decrease in the ability of spatial learning and memory in immature rats.

OBJECTIVEPsoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.

METHODUsing molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.

RESULTMolecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.

CONCLUSIONDhd can selectively suppress RORγt transcriptional activity.

Digoxin ; analogs & derivatives ; pharmacology ; Humans ; Models, Chemical ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; antagonists & inhibitors ; genetics ; Transcription, Genetic

Objective : To investigate the effect of Rotundic acid (RA) on proliferation，migration and invasion a- bility of human lung adenocarcinoma cells as well as its possible mechanisms． Methods : Human lung adenocarci- noma A549 and PC9 cells were divided into control group，blank control group，solvent group and 20，40，60，80 μmol / L RA groups．CCK-8 assay and scratch assay were used to detect the proliferation and horizontal migration of human lung adenocarcinoma cells．Transwell migration assay and Transwell invasion assay were used to detect the longitudinal migration and invasion ability of A549 and PC9 cells in each group．The protein expression levels of ja- nus kinase 2 (JAK2) and signal transducer and activator of transcription 3 ( STAT3) in the supernatants of A549 and PC9 cells were detected by ELISA．The mRNA expression levels of JAK2 and STAT3 were detected by RT- PCR. Statistical analysis was made on the differences among groups in each index. Results : After RA treatment on human lung adenocarcinoma cells ，compared with the control group ，the proliferation activity of A549 and PC9 cells in the experimental groups decreased (P＜0. 05) ，the number of cells crossing polycarbonate membrane and matrix glue decreased (P＜0. 05) ，the expression of JAK2 and STAT3 proteins in cell supernatant decreased (P < 0. 05) ，and the mRNA expression of JAK2 and STAT3 decreased (P＜0. 05) ．The decrease of the above indices was concentration-dependent and had statistical significance (P＜0. 05) ．Compared with the control group，the pro- liferation activity of A549 and PC9 cells in the solvent group showed no significant difference． Conclusion RA may inhibit the proliferation，migration and invasion of human lung adenocarcinoma A549 and PC9 cells in vitro， possibly through the inhibition of JAK2 / STAT3 pathway.