Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

Females' perception of date rape: an examination of two contextual variables

This study examined the role of perceived token resistance and previous sexual contact on women's ability to discriminate when a female wants her partner to stop his sexual advances. Participants included 101 White female undergraduate students and were randomly assigned to one of the four conditions: 1) perceived resistance with genital contact; 2) no resistance with genital contact; 3) perceived resistance with no genital contact; and 4) no resistance without genital contact. Subjects listened to an audiotaped date rape after being informed of the couple's sexual history based on the condition assigned to them. They were also informed that the couple had been on five previous dates, in which the man had manipulated the woman's breasts or genitals. In addition, the woman did not object to this contact, or the woman initially objected to the contact but subsequently stopped resisting contact. Participants in the perceived token resistance conditions took significantly longer to determine when the man should refrain from attempting further sexual contact. The findings of this study could be used to increase information on date rape, to educate individuals about the responses associated with date rape, and to reinforce rules concerning appropriate sexual behavior.     

Rapid and sensitive enzyme-linked immunosorbent assay for the microsomal epoxide hydrolase

A rapid and sensitive indirect enzyme-linked immunosorbent assay(ELISA) was developed for micrsomal epoxide hydrolase of ratliver. The assay, which is easily and readily performed, issignificantly more sensitive than most enzymatic epoxide hydrolaseassays routinely used and electroimmunoassays previously developed.The limit of sensitivity of the ELISA is between 2–5 ngof microsomal epoxide hydrolase. Using the ELISA microsomalepoxide hydrolases of mouse and rat liver were shown to be antigenicallyvery similar, while microsomal epoxide hydrolases of guineapig, monkey and human liver are antigenically distinct fromthose of rat and mouse. The ELISA developed here is capableof detecting microsomal epoxide hydrolase of rat and mouse livereven when significant enzymatic activity is lost. These resultsindicate that the antigenic sites recognized by the antibodiesused are distinct from the catalytic site of the epoxide hydrolase.Approximately 1.9% of rat microsomal protein was quantifiedas microsomal epoxide hydrolase by the ELISA. Low levels ofmicrosomal epoxide hydrolase were also detected in rat livercytosol (0.02% of the cytosolic protein) demonstrating thatmicrosomal epoxide hydrolase is not totally membrane bound orthat an immunologically related protein occurs in the cytosolof normal rat liver. The ELISA developed here will be valuablein investigating further the role of microsomal epoxide hydrolase.     

肝胆管结石肝部分切除临床效果探讨

目的:探讨肝部分切除术在肝胆管结石中的临床效果。方法:选取70例肝内胆管结石患者,随机分为治疗组和对照组各35例,治疗组采用肝部分切除术治疗,对照组采用传统开放手术(高位肝总管切开)治疗。比较2组疗效及预后。结果:治疗组术中出血量、ALT、AST、TBIL峰值及住院时间优于对照组(P<0.05),术后残石率、并发症发生率及复发率低于对照组(P<0.05)。结论:肝部分切除治疗肝胆管结石疗效确切,能缩短康复周期,降低术后残石率与并发症率,并减少复发。     

Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor,ERK, and Nrf2-Related Antioxidant Potential

Background:

We demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment.

Methods:

First, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin.

Results:

Treatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice.

Conclusions:

Melatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential.     

Propensity-Matched Analysis To Compare the Therapeutic Efficacies of Cefuroxime versus Cefotaxime as Initial Antimicrobial Therapy for Community-Onset Complicated Nonobstructive Acute Pyelonephritis Due to Enterobacteriaceae Infection in Women

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by Enterobacteriaceae infections. The clinical characteristics and outcomes of a cefuroxime-treated group (n = 156) were compared with those of a cefotaxime-treated group (n = 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%, P = 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) (P > 0.999) and 89.5% (68/76) versus 90.7% (68/75) (P = 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-β-lactamase-producing Enterobacteriaceae, C-reactive protein levels of ≥15 mg/dl, and white blood cell counts of ≥15,000/mm³ of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women.     

Comparison of the MicroScan system and the agar dilution assay for Quinupristin/Dalfopristin susceptibility of Enterococcus faecium

We compared the results of Quinupristin/Dalfopristin (Q/D) susceptibility tests by the Positive Combo Panel (Type 11) of the MicroScan Walk Away 96 analyzer (Dade Behring, Inc.) with those obtained by the reference agar dilution method. From September 2003 to August 2004, a total of 410 E. faecium isolates were obtained from clinical samples. Of these, 65 (15.9%) strains were non-susceptible, and 345 (84.1%) strains were susceptible to Q/D. We collected consecutively 65 Q/D non-susceptible E. faecium isolates (42 resistant, 23 intermediate), and randomly selected 32 Q/D susceptible E. faecium isolates using the MicroScan system. The minimal inhibitory concentrations (MICs) of Q/D, vancomycin, and teicoplanin were determined by the agar dilution method according to CLSI guidelines. The agreement rates between the two methods were 100% for Q/D-susceptible strains, 85.7% for Q/D-resistant strains, and 26.1% for Q/D-intermediate strains of E. faecium. The major error rate (S-->R) was 11.9%, and the minor error rate (S-->I) was 13.0%. No very major errors were found. We conclude that for MicroScan 'non-susceptible' test results for Q/D, it is necessary to confirm the result using a reference method. The Q/D-resistance rate was higher in glycopeptide-susceptible (78.0% for vancomycin, 82.0% for teicoplanin) than glycopeptide-resistant E. faecium (22.0% for vancomycin, 16.0% for teicoplanin). Further studies are needed to determine whether Q/D use in hospitals or virginiamycin use in animals, or other factors, are responsible for the high rates of glycopeptide-susceptible and Q/D-resistant E. faecium strains in Korea.     

情绪性量表在公务员中的信效度评价

目的评价中国成年人情绪性量表在我国公务员中的信效度。方法用情绪性量表在我国公务员群体中进行施测,通过项目分析、探索性因子分析和验证性因子分析对量表的信效度进行检验。结果经项目分析和探索性因子分析,情绪性量表表达性因子的7个项目被删除,量表保留了愉悦性和乐观性2个因子20个项目。20个项目的题总相关系数均大于0.4,因子载荷大于0.4,共同性大于0.16。2个因子可累积解释量表总变异量的57.821%。20项量表的建构效度、收敛效度、区别效度和效标效度也都符合心理测量学的要求。量表的内部一致性信度Cronbach'sα系数为0.902,愉悦性和镇定性2个因子的Cronbach'sα系数分别为0.918、0.919;愉悦性和镇定性2个因子的组合信度分别为0.919、0.848。结论情绪性量表(20项)具有良好的信效度,可以作为测量和评估我国公务员情绪性的工具。     

Relationship between stroke etiology and collateral status in anterior circulation large vessel occlusion

Journal of Neurology - Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis...