脑室内注射胰岛素改善心肺复苏后大鼠神经功能及其机制的研究

目的：观察脑室内注射胰岛素对心肺复苏（CPR）后大鼠海马CA1区神经元Caspase-3mRNA表达、神经元凋亡及神经功能的影响。方法：将30只雄性SD大鼠随机分为对照组、复苏组及胰岛素组,并采用室颤法制备大鼠CPR模型。结果：①大鼠CPR后24 h和72 h胰岛素与复苏组相比胰岛素抑制促凋亡基因Caspase-3 mRNA表达,胰岛素与复苏组Caspase-3基因表达分别为（CPR 24 h）0.43±0.03,1.39±0.36,P=0.01;（CPR 72 h）0.63±0.06,1.08±0.05,P=0.001;②大鼠CPR后7 d,胰岛素组凋亡细胞计数（92.79±7.50/mm2）明显低于复苏组凋亡细胞计数（124.75±17.35/mm2）（F=5.853,P=0.02）;③大鼠CPR后24 h,胰岛素组神经功能评分明显高于复苏组[（70（64-72）,56（50-58）;P〈0.001]。结论：胰岛素抑制CPR后大鼠神经元Caspase-3mRNA的表达,从而抑制神经元凋亡,改善神经功能,保护神经系统。     

Mean platelet volume and coronary artery disease: a systematic review and meta-analysis

Background

Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV.

Methods

Medline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data.

Results

Forty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70 fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84 fL (95% CI: 0.63, 1.04) and 0.46 fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥ 7.3 fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58).

Conclusion

Larger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.     

Epidemiological profile of Wolff–Parkinson–White syndrome in a general population younger than 50 years of age in an era of radiofrequency catheter ablation

Background

The prevalence of Wolff–Parkinson–White (WPW) syndrome varies between 0.68 and 1.7/1000. The epidemiological profile may be modified after the introduction of transcatheter interventions.

Objectives

The aim of this study is to investigate the epidemiological trends of the WPW syndrome in a general population during a period with available and reimbursed transcatheter ablation.

Methods and results

Data of WPW patients < 50 years old were retrieved from our national database (2000–2010). We identified 6086 (61% male) patients, accounting for an overall prevalence of 0.36/1000 with a peak of 0.61/1000 in ages 20–24 years. The risk of death and sudden death was 0.071% and 0.02% per patient-year, respectively. The 42 deaths occurred at a median age of 29 years. Associated congenial heart disease was noted in 158 (2.6%) patients, including 42 with Ebstein's anomaly that increased the mortality risk (P = 0.001, OR = 8.5). In those without congenital heart disease, myocardial dysfunction occurred in 115 (1.9%) patients and increased the risk of death (P < 0.001, OR = 10.6) and sudden death. Radiofrequency catheter ablation was performed in 2527 patients at a median age of 25.7 years (4.54% per patient-year, discharge mortality 0.16%); 11 (0.4%) before the age of 5, and 2231 (88%) after the age of 15. Whereas repeated ablation procedures accounted for 6.0% of the procedures, those in Ebstein's patients were 25%.

Conclusion

Radiofrequency catheter ablation is already a common treatment for WPW patients, particularly during young adulthood, which accounts for a lower prevalence. Myocardial dysfunction and associated congenital heart disease remain as risks of mortality.     

Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m²). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.     

Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM

Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.