Intracellular [Ca+ + ]i was examined using Quin-2. Resting [Ca+ + ]i in platelets loaded with Quin-2 in media containing either 1 mmol/L CaCl2. or 2 mmol/L EGTA was 52.1?5.2nmol/L, 28.4+5.1 nmol/L, respectively. The concentration of external calcium appears to play an important role in cytosolic Cat++ hemeostasis in platelets. Stimulation with A2 3187( 25nmol/L ) caused [Ca++]i to peak at 145?30.8 nmol/L in the presense of extracellular 1mmol/L CaCl2 and 34.4?2.4 nmol/L after addition of 2 mmol/L EGTA. These data suggested that the most of this rise results from calcium entry across the plasma membrane, with a small contribution to the discharge of intracellular pool of Ca++.Anisodamine ( 100?mol/L ) had no effects on resting [Ca + + ]i and A23187-evoked [Ca++]i level in the absence of CaCl2, Anisodamine ( 100?mol/L, 25?mol/L), verapamil ( 10?mol/L ) decreased the A23187 -evoked [Ca++ ]i rises in the presence of CaCl2 by 38%, 34%, 25%, respectively. These results provided a mechanism for the calcium antagonistic effects of Anisodamine.

Akt is the downstream target protein of phosphatidylinositol 3-kinase(PI3K),and PI3K/Akt signaling pathway is involved in cell proliferation,differentiation,apoptosis and metabolism.The activities of Akt in the central nervous system is also regulated by the neurotransmitter dopamine(DA),therefore Akt mediates multiple drug addiction process.This article reviews the structural characteristics and activity regulation of Akt,as well as the related research in drug addiction of this signal molecule.

Daphnetin, isolated from Daphne koreane Nakai, has been reported to dilate blood vesse ls, inhibit thrombosis and have antiinflammatory effect. In this study, type Ⅰ and type Ⅱ protcin kinase A partially purified from rat skeletal muscle and protein kinase C from rat brain were incubated with varying concentrations of daphnetin. Type Ⅱ protein kinase A was siguificantly inhibited by daphnetin at the concentration of 0.0056?mol/L, while type Ⅰ protein kinase A and protein kinasc C were inhibitcd at the concentrations of 5.6?mol／L and 56 ?mol/L, respectively. The results indicated that daphnetin might be used as a specific inhibitor of type Ⅱ protein kinase A

Basic and cIinicaI studies demonstrate that depression is associated with abnormaI neuraI pIasticity in some brain regions,incIuding the prefrontaI cortex and hippocampus. Brain-derived neurotro-phic factor(BDNF)and its signaIing pathways pIay a cruciaI roIe in reguIating neuraI pIasticity and deveI-opment of depression. Ketamine or scopoIamine can produce a quick and sustained antidepressant effect,and both can quictIy activate BDNF-signaIing pathways reIated to neuraI pIasticity. In order to pro-vide the theoreticaI basis for future researches on new antidepressants,the neuraI pIasticity mechanisms of faster-onset antidepressants are reviewed in this paper.

[Objective]To explore the value of different surgical methods in the treatment of the displaced femoral neck fracture in the elderly.[Method]A follow up study was done on 95 cases older than 65 years who were treated with internal fixation,femoral head arthroplasty and total hip joint replacement from 2003 to 2008.The differenee upon operation time,blood loss,duration of hospitalization,joint function evaluation one and two years after operation,complications and reoperation rate were compared.[Result]The internal fixation group had the shortest operation time and hospitalization and the least blood loss but the highest immobilization time,highest co-mplication rate and reoperation rate as we1l as the worst joint function.While the total hip joint repl acement group had the least immobilization time,the lowest compliction rate and reoperation rate,best joint function but required better health condition.The femoral head arthroplasty group had the least operation injury but had relative higher reoperation rate and worse joint function compared to the total hip joint replacement group.[Conclusion]Prosthetic replacement is reliable to treat femoral neck fractures in the elderly.

Glenohumeral subluxation is one of the most frequent complications in patients with post-stroke hemiplegia. This paper reviewed the recent advances in research on post-stroke Glenohumeral subluxation from the epidemiology, pathogenesis and related factors, diagnosis,treatment and so on.

Objective To study the distribution and drug resistance of pathogens in neonatal septicemia in order to provide clinical guidance for antibiotic usage.Methods This retrospective study analyzed blood culture and clinical data from 83 confirmed neonatal septicemia patients and the blood collection cultures were analyzed.Results A total of 84 strains were isolated from 83 cases of blood specimens,Gram positive bacteria,Gram negative bacteria and fungi were 38(45.2%),41(48.8%),5(6.0%),respectively.Gram positive bacteria was mainly coagulase negative staphylococcus and staphylococcus aureus,which were 13(15.5%) and 8(9.5%) respectively.Gram negative bacteria was mainly Escherichia coli and Klebsiella pneumonia,which were 25(29.8%) and 9(10.7%) respectively.Gram positive bacteria were found high resistance to penicillin G,amoxicillin clavulanate potassium,oxacillin and clindamycin,from 34.2% to 73.7%,but they were sensitive to vancomycin,teicoplanin and linezolid.Gram negative bacteria were found high resistance to ampicillin(82.9%),the constituent ratio of the extended spectrum βlactamases(ESBLs) was 34.1%,carbapenem resistant strains was not found.All fungi were sensitive to azoles.Conclusion Gram negative bacteria are the major pathogens in neonatal septicemia,with high infection rate of Escherichia coli and high constituent ratio of the ESBLs,and antimicrobial agents should be chosen according to blood culture and antimicrobial susceptibility results.

BACKGROUND: Serious scalding leads to dysfunction of each aspect in immune system, and activated macrophage can secret many bioactive transmitters. The relationship between macrophage dysfunction and signal conduction after scalding is unclear at present.OBJECTIVE: To observe the alternation of tumor necrosis factor- alpha(TNF-α) at different time points after scalding and the activity of nuclear factor κB(NF-κB) and alternation of protein kinase C (PKC) after the application of specific modulator H-7 to explore whether PKC participates in the modulation of TNF-α in macrophage on signal conduction level for the clarification of some mechanisms of macrophage dysfunction.DESIGN: A randomized controlled experimental study by employing experimental animals as subjectsSETTING: An institute of burn research of a military medical university MATERIALS: The study was conducted in the Laboratory (state) of the Institute of Burn Research, Third Military Medical University of Chinese PLA between January and December 1999. Experimental animals were 32 healthy clean inbreeding Kunming white mice.METHODS: 15% Ⅲ scalding was created in mice for the establishment of routine scalding model. Mice were randomly divided into 6 groups according to different time points before or after scalding, I.e. 0(normal control group), 2, 6, 12, 24, or 48 hours group. Celiac macrophages were collected for the detection of TNF-α content by radioimmunoassay, NF-κB activity by electrophoretic mobility shift analysis (EMSA), and membrane or plasma PKC activity by isotope analysis.MAIN OUTCOME MEASURES: ① TNF-α content; ② NF-κB activity; ③Membrane or plasma PKC activity RESULTS: After scalding, macrophage excessively secreted TNF-α and reached its peak of (1 085.65 ± 122.99) ng/L at 12 hours, which was significantly higher than that of control group( t = 14.92, P ＜ 0.01 ).Compared with control group, membrane PKC activity increased after scalding, which significantly heightened to(231.80 ± 31.66) nmol/min · g at 2hours( t = 7. 930, P ＜ 0.01 ), slightly decreased to close to normal level of (174.29±16.80) nmol/min· gat 6hours(t=2.531, P ＜0.05), and rapidly elevated at 12 hours [512. 10 ±33.42) nmol/min · g] and 24 hours [ (454.70 ± 21.06) nmol/min · g] to reach its peak of(530.49 ± 28.54)nmol/min. G at 48 hours( t = 29.42, 28.03, 30. 19, P ＜ 0. 01 ). Correlation analysis of the alternation between TNF-α and membrane PKC indicated a significant positive correlation( r = 0. 796 4, P ＜ 0. 05) . As indicated by EMSA image, NF-κB activity significantly elevated after scalding. Twelve hours after scalding was set as modulation point, NF-κB activity was significantly inhibited by the application of H-7.CONCLUSION: The secretion of TNF-α and the activities of PKC and NF-κB are significantly activated in celiac macrophage after scalding, and PKC-NF-κB signal pathway participates in the modulation of TNF-α expression, which provide experimental data for the modulation of immune function and rehabilitative intervention during scalding.serious scalding.

BACKGROUND: Severe scald injury leads to a variety of disorders in the immune system. Activated macrophages are known to secrete many kinds of biologically active transmitter, but the relation between the functional disorder of the macrophages and signal transduction after burn injury has not been fully understood.OBJECTIVE: To observe the changes in nuclear factor(NF) -κκB activity and expressions of IκκB-α and tumor necrosis factor(TNF) -α in peritoneal macrophage of mice at different time points after severe scald injury and after the application of specific NF-κκB inhibitor pyrrolidine dithiocarbamate (PDTC), thereby to explore the mechanism of macrophage dysfunction in light of signal transduction.DESIGN: A randomized controlled experimental research.SETTING: State Key Laboratory of Trauma, Burn and Combined Injury.MATERIALS: The experiment was carried out in the State Key Laboratory of Institute of Burn Research, Third Military Medical University during the period from January to June, 1999, using 30 healthy clean-grade Kunming mice of inbred strain.INTERVENTIONS: Common scald injury models(with third degree burn of 15% total body surface area) were established in the mice, which were randomized into 6 groups according to different time points after the injury for observation, namely 0 hour(normal control group) and postburn 2, 6, 12,24 and 48 hours. Peritoneal macrophages were collected at these time points for examining TNF-α content using radio-immunoassay and NF-κκB activity by means of electrophoretic mobility shift assay(EMSA). The expressions of IκκB-α and TNF-α mRNA were determined by immunoblotting method and reverse transcription-PCR, respectively.MAIN OUTCOME MEASURES:Examinations of ① the content of TNF-α, ② NF-κκB activity,③ expression of IκB-α, and ④ expression of TNF-α mRNA.RESULTS: Macrophage secretion of TNF-α was enhanced postburn, reaching the peak level at 12 hours[(1085.65 ± 122.99) ng/L], which was significantly higher than that in the normal control group( t = 14.92, P ＜ 0.01) .Postburn NF-κκB activity significantly increased after the injury, peaking at 2 hours[ (56. 8 ± 7.3)RDU], which occurred much earlier than the peak of TNF-α secretion( t=13. 31, P ＜ 0.01 ). Compared with that in the normal control group, IκB-α expression decreased significantly 2 hours postburn ( t =4. 23, P ＜ 0. 01) to 0. 632 ±0. 086, followed by gradual increase to the peak level to 1. 161 ± 0. 097 24 hours after the burn injury( t = 7.06, P＜ 0. 01) and then by slight decrease to 1. 149 ±0. 167 till 48 hours(t = 4. 82, P ＜ 0.01) . Twelve hours after injury was the time point for intervention with PDTC application, when NF-κκB activity and TNF-α mRNA expression both decreased significantly( P ＜ 0.01 ).CONCLUSION: NF-κB activity and TNF-αmRNA expression decrease significantly after severe scald. At high levels, IκB-α and NF-κκB maintain an interaction for their restriction. After burn injury, NF-κκB signal transduction pathway is involved in the modulation of TNF-α expression in mouse peritoneal macrophage.

ObjectiveTo evaluate the discriminative stimulus effects of nicotine on the basis of a rat model of heroin discrimination.MethodsMale Sprague-Dawley rats were trained to discriminate 0.3 mg/kg heroin from saline under a fixed-ratio (FR10) schedule of food reinforcement.After training,different doses of heroin and nicotine were used to substitute for training dose of heroin,the dose-response curve for heroin and the discriminative stimulus effects of nicotine were identified in rats.ResultsAll rats reliably discriminated 0.3 mg/kg heroin from saline.Different doses of heroin ( 0.03,0.1,0.3,0.56 mg/kg ) produced ( 33.9 ± 15.0 ) ％,( 43.3 ± 13.3 ) ％,(98.7 ± 0.5 ) ％,(99.4 ± 0.2 ) ％ total responding on heroin associated lever,heroin at the doses of lower than 0.3 mg/kg produced the dose-dependent relationship in heroin-appropriate responding.In heroin-trained rats,nicotine at the dose of 0.03,0.1 mg/kg produced(1.9 ±1.1)％,(13.7 ±5.6)％ total responding on heroin associated lever,there were extremely significant differences with 0.3 mg/kg heroin control (P＜0.01).However,nicotine at the dose of 0.3,0.5 mg/kg produced ( 60.4 ± 16.1 ) ％,(65.9 ± 16.4) ％ total responding on heroin associated lever,there were no significant differences with 0.3 mg/kg heroin control (P＞ 0.05 ).ConclusionNicotine at the dose of 0.3,0.5 mg/kg can partially produce heroin-like discriminative stimulus effects.