Melatonin Prevents Oxidative Stress and Hepatocyte Cell Death Induced by Experimental Cholestasis

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.     

Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study

Background

The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.

Methods

Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162). Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).

Results

Expression of CD11b was increased on circulating neutrophils from smokers with COPD. It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05). In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).

Conclusions

Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers.     

儿童阻塞性睡眠呼吸暂停低通气综合征与肥胖的相关性研究

目的:探讨儿童阻塞性睡眠呼吸暂停/低通气综合征(OSAHS)与肥胖的相关性。方法:收集单纯性肥胖儿童120例和体重正常儿童110例作为研究对象,进行统一的体格检查和专科检查,并进行多导睡眠监测记录阻塞性呼吸暂停指数(OAI)、呼吸暂停/低通气指数(AHI)、中枢性呼吸暂停指数(CAI)、最低血氧饱和度(LSa O2)和睡眠效率。结果:肥胖组OSAHS患病率为58.33%显著高于对照组的31.82%,差异有统计学意义(P0.05);OAI、AHI、CAI均显著高于对照组,而LSa O2、睡眠效率指标显著低于对照组,差异均有统计学意义(均P0.05);多因素回归分析显示,肥胖、扁桃体增生、腺样体增生是导致OSAHS的独立危险因素,差异有统计学意义(均P0.05)。结论:肥胖是儿童OSAHS发病的重要影响因素,特别是合并扁桃体肿大或腺样体肿大的患儿应注意预防OSAHS的发生。     

Role of electroencephalogram and oxygen saturation in the induction mechanism of arousal for obstructive sleep apnea-hypopnea syndrome patients

Arousal concomitant with obstructive sleep apnea-hypopnea syndrome (OSAHS) is known to result in sleep fragmentation and excessive daytime sleepiness. The cause of arousal is multifarious, and the mechanism is not yet clear. The aim of this study was to further research the induction mechanism of arousal by investigating the variation of electroencephalogram (EEG) and oxygen saturation (SaO₂). This study enrolled 20 subjects with a clinical diagnosis of OSAHS who underwent overnight polysomnography. Respiratory events and arousals were scored, and individuals with insufficient samples (<30) were excluded. Thus, 13 subjects mostly with severe OSAHS were analyzed in this study. The wavelet coefficients, spectral power of EEG (C4-M1 and C3-M2) before arousal or airway reopening, and the maximum desaturations of SaO₂ during respiratory events were analyzed. For most subjects, EEG (in stages N1 and N2) during respiratory events with arousals exhibited significantly lower values of wavelet coefficients and spectral power (p < 0.05). The maximum desaturations of SaO₂ during respiratory events with arousals are larger than those without among individual. In binary logistic regression analysis, the P values of EEG features and SaO₂ desaturation were both less than 0.001. Our results demonstrate that in light NREM stage, less activity in EEG during respiratory events and larger SaO₂ drop both independently were related to the occurrence of arousal. These significant differences come from major subjects based on the statistical analysis, and help supplement the induction mechanism of arousal.     

OSAHS风险对患者静脉麻醉术后认知功能障碍的影响

目的:探讨OSAHS风险与静脉麻醉手术患者术后发生认知功能障碍的关系。方法:采用No SAS评分对55例静脉麻醉手术患者进行OSAHS风险评估,并将其分为对照组23例(NoSAS 8分)和OSAHS组32例(No SAS≥8分),以蒙特利尔认知评估量表(MoCA)对两组患者在术前和术后第一天进行认知功能评估,计算每位患者手术前后Mo CA评分的差值△Mo CA(术前MoCA-术后MoCA),比较两组患者手术前后的MoCA评分及△MoCA。结果:OSAHS组术前MoCA评分(25.83±1.80)明显低于对照组术前MoCA评分(28.05±1.31)(P0.05)。OSAHS组术后MoCA评分(25.13±1.64)较术前无明显变化(P0.05),对照组术后Mo CA评分(26.73±1.17)明显低于术前(P0.05)。OSAHS组△MoCA(0.39±1.03)明显低于对照组(1.32±1.08),主要表现为视空间与执行功能[(0.09±0.29) vs.(0.30±0.32)]、注意力[(0.09±0.60) vs.(0.47±0.70)]和延时回忆力[(0.17±0.39) vs.(0.47±0.51)]两方面(P0.05)。结论:OSAHS高风险患者静脉麻醉术后认知功能障碍的程度较OSAHS低风险人群显著降低。     

不同低氧时间对SD大鼠颏舌肌肌纤维类型的影响

目的:观察不同低氧时间大鼠颏舌肌肌纤维类型的变化。方法:建立低氧模型,血气分析证实模型成功建立。在低氧不同时间点分别取低氧组和正常组雄性SD大鼠颏舌肌进行HE染色,肌球蛋白ATP酶组织化学染色和RT-PCR检测肌纤维类型的变化。结果:血气分析结果证实低氧组氧分压与血氧饱和度较对照组发生明显下降(P0.05)。低氧1周组、2周组、3周组、4周组较正常组氧分压下降至55.04±2.31 mm Hg,52.69±1.51 mm Hg,49.80±1.39 mm Hg,50.11±3.02 mm Hg(P0.05);血氧饱和度下降至77.51±1.81%,70.13±2.90%,74.20±1.95%,74.97±2.36%(P0.05)。HE染色和肌球蛋白ATP酶组织化学染色法显示低氧2、3、4周组Ⅱ型肌纤维所占比例较相应正常组依次升高:45.92±1.8%,57.44±2.1%,56.89±2.6%,在第三周时达到顶峰(P0.05)。RT-PCR结果也同样验证了这一规律。结论:随着低氧活动的进行,颏舌肌肌纤维类型发生有规律的转化,从而影响着肌肉的功能。     

Videodensitometric time-density curve change after alcohol septal ablation of obstructive hypertrophic cardiomyopathy

A recently developed computerized method for estimation of myocardial perfusion, based on the analysis of the time-density curves, is demonstrated to assess myocardial blush over a selected myocardial region of interest in a patient with obstructive hypertrophic cardiomyopathy before and after alcohol septal ablation.     

High CO2 Levels Cause Skeletal Muscle Atrophy via AMP-activated Kinase (AMPK), FoxO3a Protein,and Muscle-specific Ring Finger Protein 1 (MuRF1)

Patients with chronic obstructive pulmonary disease, acute lung injury, and critical care illness may develop hypercapnia. Many of these patients often have muscle dysfunction which increases morbidity and impairs their quality of life. Here, we investigated whether hypercapnia leads to skeletal muscle atrophy. Mice exposed to high CO₂ had decreased skeletal muscle wet weight, fiber diameter, and strength. Cultured myotubes exposed to high CO₂ had reduced fiber diameter, protein/DNA ratios, and anabolic capacity. High CO₂ induced the expression of MuRF1 in vivo and in vitro, whereas MuRF1^−/− mice exposed to high CO₂ did not develop muscle atrophy. AMP-activated kinase (AMPK), a metabolic sensor, was activated in myotubes exposed to high CO₂, and loss-of-function studies showed that the AMPKα2 isoform is necessary for muscle-specific ring finger protein 1 (MuRF1) up-regulation and myofiber size reduction. High CO₂ induced AMPKα2 activation, triggering the phosphorylation and nuclear translocation of FoxO3a, and leading to an increase in MuRF1 expression and myotube atrophy. Accordingly, we provide evidence that high CO₂ activates skeletal muscle atrophy via AMPKα2-FoxO3a-MuRF1, which is of biological and potentially clinical significance in patients with lung diseases and hypercapnia.     

COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

Background

There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.

Methods

Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.

Results

Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.

Conclusions

Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.

Trial Registration

SCO104960, clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00292552","term_id":"NCT00292552"}}NCT00292552     

结缔组织生长因子在慢性阻塞性肺疾病血管重建中表达研究

目的：探讨结缔组织生长因子（CTGF）在慢性阻塞性肺疾病（COPD）血管重建中的表达及意义。方法：将30例有吸烟史的男性鳞癌需要手术的患者按其肺功能结果分成二组,对照组：（肺功能正常组）;COPD稳定期组：（肺功能异常组）,每组15例,标本来自于癌旁的肺组织,肺血管重塑的形态学观察行HE和MASSON三色染色,行免疫组化来观察CTGF蛋白、PCNA蛋白在肺血管平滑肌中的表达。结果：（1）COPD组肺动脉管壁面积/管总面积（WA%）、管壁的胶原厚度、肺动脉平滑肌中CTGF蛋白及PCNA蛋白的表达与对照组相比差异有统计学意义。（2）CTGF与管壁面积/管总面积（WA%）、管壁的胶原厚度及血管平滑肌中PCNA表达呈正相关（,r值分别为0.81、0.68、0.86,P〈0.05）。吸烟指数与管壁面积/管总面积及PCNA的表达呈正相关（r=0.73,0.99,P〈0.01）。结论：单纯吸烟者即有血管重建,吸烟伴COPD者血管重建更加严重,CTGF在COPD患者肺血管中的表达较对照组高,可能参与了COPD血管重建过程。