Differences in mRNA Expression,Protein Content,and Enzyme Activity of Superoxide Dismutases in Type II Pneumocytes of Acute and Chronic Lung Injury

The lung is protected against oxidative stress by a variety of antioxidants and type II pneumocytes seem to play an important role in antioxidant defense. Previous studies have shown that inhalation of NO₂ results in acute and chronic lung injury. How the expression and enzyme activity of antioxidant enzymes are influenced in type II cells of different inflammatory stages has yet not been studied. To elucidate this question, we exposed rats to 10 ppm NO₂ for 3 or 20 days to induce acute or chronic lung injury. From these and air-breathing rats, type II pneumocytes were isolated. The mRNA expression and protein content of CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined. For the acute lung injury (3 d NO₂), the expression of CuZnSOD mRNA was significantly increased, while MnSOD expression was significantly reduced after 3 days of NO 2 exposure. For the chronic lung injury (20 d NO₂), CuZnSOD expression was still enhanced, while MnSOD expression was comparable to control. In parallel to CuZnSOD mRNA expression, the protein amount was significantly increased in acute and chronic lung injury however MnSOD protein content exhibited no intergroup differences. Total SOD enzyme activity showed a significant decrease after 3 days of NO₂ exposure and was similar to control after 20 days. We conclude that during acute and chronic lung injury in type II pneumocytes expression and protein synthesis of CuZnSOD and MnSOD are regulated differently.     

Acute toxicity,critical body residues,Michaelis–Menten analysis of bioaccumulation,and ionoregulatory disturbance in response to waterborne nickel in four invertebrates: Chironomus riparius, Lymnaea stagnalis, Lumbriculus variegatus and Daphnia pulex

We investigated the bioaccumulation and acute toxicity (48 h or 96 h) of Ni in four freshwater invertebrate species in two waters with hardness of 40 (soft water) and 140 mg L^− 1 as CaCO₃ (hard water). Sensitivity order (most to least) was Lymnaea stagnalis > Daphnia pulex > Lumbriculus variegatus > Chironomus riparius. In all cases water hardness was protective against acute Ni toxicity with LC50 values 3–3.5 × higher in the hard water vs. soft water. In addition, higher water hardness significantly reduced Ni bioaccumulation in these organisms suggesting that competition by Ca and Mg for uptake at the biotic ligand may contribute to higher metal resistance. CBR50 values (Critical Body Residues) were less dependent on water chemistry (i.e. more consistent) than LC50 values within and across species by ~ 2 fold. These data support one of the main advantages of the Tissue Residue Approach (TRA) where tissue concentrations are generally less variable than exposure concentrations with respect to toxicity. Whole body Ni bioaccumulation followed Michaelis–Menten kinetics in all organisms, with greater hardness tending to decrease B_max with no consistent effect on K_d. Across species, acute Ni LC50 values tended to increase with both K_d and B_max values — i.e. more sensitive species exhibited higher binding affinity and lower binding capacity for Ni, but there was no correlation with body size. With respect to biotic ligand modeling, log K_NiBL values derived from Ni bioaccumulation correlated well with log K_NiBL values derived from toxicity testing. Both whole body Na and Mg levels were disturbed, suggesting that disruption of ionoregulatory homeostasis is a mechanism of acute Ni toxicity. In L. stagnalis, Na depletion was a more sensitive endpoint than mortality, however, the opposite was true for the other organisms. This is the first study to show the relationship between Na and Ni.     

Tumour necrosis factor-α and soluble Fas ligand as biomarkers in non-acetaminophen-induced acute liver failure

Arylamines and nitroarenes are very important intermediates in the industrial manufacture of dyes, pesticides and plastics, and are significant environmental pollutants. The metabolic steps of N-oxidation and nitroreduction to yield N-hydroxyarylamines are crucial for the toxic properties of arylamines and nitroarenes. Nitroarenes are reduced by microorganisms in the gut or by nitroreductases and aldehyde dehydrogenase in hepatocytes to nitrosoarenes and N-hydroxyarylamines. N-Hydroxyarylamines can be further metabolized to N-sulphonyloxyarylamines, N-acetoxyarylamines or N-hydroxyarylamine N-glucuronide. These highly reactive intermediates are responsible for the genotoxic and cytotoxic effects of this class of compounds. N-Hydroxyarylamines can form adducts with DNA, tissue proteins, and the blood proteins albumin and haemoglobin in a dose-dependent manner. DNA and protein adducts have been used to biomonitor humans exposed to such compounds. All these steps are dependent on enzymes, which are present in polymorphic forms. This article reviews the metabolism of arylamines and nitroarenes and the biomonitoring studies performed in animals and humans exposed to these substances.     

Dynamic changes in serum angiopoietin-1, angiopoietin-2, and angiopoietin-2/angiopoietin-1 ratio in acute myocardial infarction patients treated with primary percutaneous coronary intervention

Context: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play divergent roles in myocardial ischemia and reperfusion injury.

Objective: To investigate serum Ang-1 and Ang-2 levels in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI).

Methods: Serum Ang-1 and Ang-2 were measured in 85 STEMI patients in the first week after PCI.

Results: Ang-1, Ang-2 and Ang-2/Ang-1 ratio (Ang-2/1) were all increased at admission, and had dynamic changes after PCI. Ang-2 and Ang-2/1 at admission and 2 h after PCI were positively correlated with peak cardiac troponin T levels.

Conclusion: The extent of myocardial damage may be linked to circulating Ang-2 and Ang-2/1.     

Acute exacerbations in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease that primarily affects older adults. Median survival after diagnosis is 2–3 years. The clinical course of IPF may include periods of acute deterioration in respiratory function, which are termed acute exacerbations of IPF (AEx-IPF) when a cause cannot be identified. AEx-IPF may represent a sudden acceleration of the underlying disease process of IPF, or a biologically distinct pathological process that is clinically undiagnosed. An AEx-IPF can occur at any time during the course of IPF and may be the presenting manifestation. The incidence of AEx-IPF is hard to establish due to variation in the methodology used to assess AEx-IPF in different studies, but AEx-IPF are believed to occur in between 5 and 10% of patients with IPF every year. Risk factors for AEx-IPF are unclear, but there is evidence that poorer lung function increases the risk of an AEx-IPF and reduces the chances of a patient surviving an AEx-IPF. The presence of comorbidities such as gastroesophageal reflux disease (GERD) and pulmonary hypertension may also increase the risk of an AEx-IPF. AEx-IPF are associated with high morbidity and mortality. Patients who experience an AEx-IPF show a worsened prognosis and AEx-IPF are believed to reflect disease progression in IPF. Current treatments for AEx-IPF have only limited data to support their effectiveness. The latest international treatment guidelines state that supportive care remains the mainstay of treatment for AEx-IPF, but also give a weak recommendation for the treatment of the majority of patients with AEx-IPF with corticosteroids. There is emerging evidence from clinical trials of investigational therapies that chronic treatment of IPF may reduce the incidence of AEx-IPF. Additional clinical trials investigating this are underway.     

无创呼吸机在慢性阻塞性肺疾病急性加重期应用的疗效评价

摘要目的：观察无创呼吸机对不伴有呼吸衰竭的慢性阻塞性肺疾病急性加重期（AECOPD）患者症状、体征、血气分析和肺功能的影响。方法：80例AECOPD患者随机分为对照组和试验组,对照组给予常规治疗,如常规抗感染、化痰、平喘等治疗。试验组在常规治疗的基础上给予无创呼吸机正压通气（NIPPV）治疗。评价两组患者治疗前和治疗一周后临床症状体征、血气分析和肺功能的变化。结果：两组患者治疗后临床症状及体征评分较治疗前均呈下降趋势（P〈0．05）,但试验组下降更为明显（P〈0．05）,并且试验组症状改善时间明显缩短（P〈0．05）;治疗后两组的pH,PO2和SaO2均较治疗前升高,PC02较治疗前下降（P〈0．05）,和对照组相比,治疗后试验组的PO：和PC02改善更明显（P〈0．05）,而pH和Sa02无显著差异（P〉0．05）;治疗后两组的FEV1,FVC,FEV1实测值／预计值和FEVI％均较治疗前升高（P〈0．05）,试验组升高更明显（P〈0．05）。结论：对不伴有呼吸衰竭的AECOPD患者早期应用NIPPV治疗能有效改善临床症状和体征,缩短症状改善时间,改善通气,缓解呼吸肌疲劳,预防呼吸衰竭的发生。     

早期肠内营养辅助治疗重症胰腺炎的临床疗效分析

目的：探讨早期肠内营养辅助治疗重症胰腺炎的临床效果。方法：选择2009年4月-2012年2月我院收治的重症胰腺炎患者共46例,随机分为实验组和对照组各23例,实验组在综合治疗的基础采用早期肠内营养治疗（EN）,而对照组在综合治疗的基础上采用全胃肠外营养治疗（TPN）,比较两组患者的血清总蛋白、白蛋白、尿素氮水平及血淋巴细胞百分比变化、血淀粉酶和尿淀粉酶恢复正常时间、住院时间及病死率,并比较两组治疗前及治疗后24、48及72小时的APACHEII评分。结果：治疗后,实验组患者的血清总蛋白、白蛋白、尿素氮水平及血淋巴细胞百分比变化均较对照组明显增高,差异有统计学意义（P〈0．05）,而血淀粉酶、尿淀粉酶恢复时间、病死率及住院时间分别均明显较对照组降低或缩短,差异有统计学意义（P〈0．05）。治疗24、48及72小时后,实验组APACHEII评分均较治疗前显著减低（P〈o．05）,而对照组治疗24、48h后APACHEⅡ评分与治疗前比较差异无统计学意义（P〉0．05）,治疗72h后APACHEII评分较治疗前显著减低（P〈O．05）。结论：采用早期肠内营养辅助治疗重症胰腺炎患者能有效保护肠黏膜屏障功能,改善患者的营养状况,增强患者的免疫力,并改善患者的预后。     

Detrimental effects of endogenous oestrogens on primary acute myocardial infarction among postmenopausal women

Objective

Traditionally, oestrogens were considered to be protective for the cardiovascular system for premenopausal women. Therefore, we conducted a retrospective case–control study to examine the association between endogenous oestrogens and acute myocardial infarction (AMI) risk among postmenopausal women.

Methods

A case–control study was performed among 30 primary AMI patients and 60 control subjects. Baseline characteristics data was collected and endogenous sex hormones levels were determined using chemoluminescence and radioimmunoassay methods. Conditional logistic regression models were developed with adjustment for confounders.

Results

Compared with controls, the circulating oestrone, oestradiol, androstenedione and testosterone levels were significantly higher in AMI patients (P < 0.05) while the sex hormone binding globulin (SHBG) level was lower (P < 0.05). Spearman correlation coefficients showed oestradiol was positively correlated with body mass index (BMI) and waist-to-hip ratio (WHR) in cases, but not in controls. In univariable conditional logistic regression models, oestrone, oestradiol, testosterone, WHR, BMI, diabetes and hypertension were all found to be positively associated with AMI (P < 0.05). After adjusting for these factors, oestradiol (odds ratio (OR) = 4.75; 95 % confidence interval (CI) = 1.07–21.10; P = 0.04) and WHR (OR = 6.46; 95 % CI = 1.09–38.39; P = 0.04) continued to demonstrate strong positive associations with AMI.

Conclusions

A higher level of oestradiol was potentially associated with primary AMI risk among postmenopausal women.