Acute Phase Immune Response to Exercise Coexists with Decreased Neutrophil Antioxidant Enzyme Defences

Long-duration or damaging exercise initiates reactions that resemble the acute phase response to infection and induces neutrophil priming for oxidative activity. Our objective was to establish the status of the antioxidant defences and of the oxidative equilibrium in the neutrophils of sportsmen prior to and after intense physical exercise. Nine voluntary male professional cyclists participated in this study. The exercise was a cycling mountain stage (171 km) and the cyclists took a mean &#45 SEM of 270 &#45 12 min to complete it. We determined the activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), the levels and activity of superoxide dismutase (SOD), the concentrations of ascorbate, glutathione and glutathione disulphide (GSSG) and DNA levels in neutrophils. The cycling stage decreased enzyme activities expressed per DNA units: CAT (33%), SOD (38%), GPx (65%); increased ascorbate concentration in neutrophils and decreased the GSH/GSSG ratio and the enzyme activities expressed per DNA units. Neutrophils could contribute to plasma antioxidant defences against oxidative stress induced by exercise because they probably provide antioxidant enzymes and ascorbate.     

心血管病患者并发肺部感染的病原菌分布及危险因素分析

目的:探讨心血管病患者并发肺部感染的病原菌分布特点及相关危险因素,以降低感染率。方法:选择2015年8月~2016年3月因心血管病入院治疗的154例患者为研究对象,收集其相关临床数据,进行回顾性分析,采集医院感染患者痰标本进行细菌培养,分析病原菌分布及危险因素。结果:154例心血管病患者并发肺部感染者25例,感染率为16.23%。共培养出病原菌27株,革兰阴性菌16株(占59.26%)、革兰阳性菌7株(占25.93%)及真菌4株(占14.81%)。单因素分析显示年龄、基础疾病、侵入性操作、抗生素使用、住院时间等与医院感染率有关,差异有统计学意义(P0.05);logistic回归分析发现,年龄(≥60岁)、有基础疾病、有侵入性操作、使用抗生素、住院时间(14天)是心血管病患者并发肺部感染的危险因素。结论:心血管病患者肺部感染的主要病原菌为大肠埃希菌、肺炎克雷伯菌以及金黄色葡萄球菌等,应针对相关危险因素进行干预,以降低医院感染率。     

Acute Phase Response in Dairy Cows with Experimentally Induced Escherichia coli Mastitis

Six Finnish Ayrshire cows were challenged intramammarily with 1500 CFU of Escherichia coli (E. coli) into single udder quarters, and the challenge was repeated into contralateral quarters 3 weeks later. All cows received flunixine meglumine once, and 3 of them were also treated with enrofloxacin. At the 2nd challenge, treatments were changed vice versa. The development of mastitis was followed by monitoring of systemic and local clinical signs, and with serial milk and serum samples. Intramarnmary challenge with E. coli produced clinical mastitis in all cows, the severity of the disease varying greatly between the animals. No significant changes between the 2 treatment regimens or sequent challenges were found for any of the clinical parameters. The response of each cow followed the same pattern after both challenges; three of the cows became mildly and the other 3 either moderately or severely affected. Two severely affected cows had to be euthanized because of severe mastitis. Serum haptoglobin and amyloid-A concentrations peaked 2–3 days after bacterial challenge. Serum haptoglobin did not correlate with the severity of the disease. Serum amyloid-A rose gradually in the severely affected cows, and significant differences were found between severely versus moderately or mildly affected cows at day 4. Serum tumor necrosis factor alpha concentrations increased only in the severely affected cows. Serum Cortisol response was prolonged in the severely diseased animals, and was significantly lower after the second challenge. Serum nitrite/nitrate concentration increased in the severely affected cows. This indicated excess nitric oxide production during acute E. coli mastitis. Strongly decreased milk production, and high bacterial growth in the infected quarters were best predictors for the outcome from acute E coli mastitis.     

不同危险分层急性肺栓塞患者D-二聚体与纤维蛋白原比值、中性粒细胞与淋巴细胞比值、白蛋白的变化及其与预后的关系研究

摘要 目的：探讨不同危险分层急性肺栓塞（APE）患者D-二聚体与纤维蛋白原比值（DFR）、中性粒细胞与淋巴细胞比值（NLR）、白蛋白（Alb）的变化及其与预后的关系。方法：选择2019年3月至2021年12月我院收治的APE患者154例作为APE组,根据《肺血栓栓塞症的诊断与治疗指南(2015)》分为低危组48例、中危组69例和高危组37例,另选择同期我院体检健康志愿者40例作为对照组,比较各组DFR、NLR、Alb水平。根据不同预后将APE患者分为存活组125例,死亡组29例,比较两组DFR、NLR、Alb水平。应用受试者工作特征（ROC）曲线分析DFR、NLR、Alb对APE预后的预测价值。结果：APE组DFR、NLR显著高于对照组,Alb水平显著低于对照组（P<0.05）。随着危险分层增加,APE患者DFR、NLR逐渐升高,Alb水平逐渐降低,不同危险分层APE患者DFR、NLR、Alb水平比较有统计学意义（P<0.05）。死亡组DFR、NLR显著高于存活组,Alb水平显著低于存活组（P<0.05）。ROC曲线分析显示,DFR、NLR、Alb对APE死亡预测具有较高的敏感度、特异度,其中DFR、NLR、Alb联合检测对APE死亡预测的曲线下面积（AUC）、敏感度、特异度最高。结论：APE患者DFR、NLR异常升高,Alb异常降低与APE危险分层增加及不良预后相关,DFR、NLR、Alb联合检测对APE患者预后不良的预测价值更高。     

急性脑梗死患者并发医院肺部感染的影响因素分析

目的:探讨急性脑梗死患者并发医院肺部感染的相关影响因素,为临床的预防与治疗提供指导依据。方法:回顾性分析我院神经科2011年1月~2013年8月收治入院的526例急性脑梗死患者的临床资料。结果:在全部526例急性脑梗死患者中,并发医院肺部感染的有79人,占15.0%。分析显示,高龄、吸烟史、糖尿病、意识障碍、吞咽困难、低蛋白血症等原因是并发肺部感染的危险因素。而从这些感染者的痰液中共分离出病原菌98株,包括铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌、金黄色葡萄球菌、表皮葡萄球菌、大肠埃希菌、白假丝酵母菌等。结论:急性脑梗死患者易并发医院肺部感染,其危险因素主要有高龄、吸烟史、糖尿病、意识障碍、吞咽困难、低蛋白血症等。     

急性脑梗塞后肺部感染的相关因素及预后

目的:分析探讨急性脑梗塞后肺部感染的相关因素及其预后,以有利于进一步预防及治疗。方法:对2009年5月至2011年5月收治的258例脑梗塞急性期患者的临床资料进行回顾性调查分析,根据是否合并肺部感染分为肺部感染组和对照组,分析肺部感染的危险因素和其预后的相关性。结果:258例脑梗塞患者中发生肺部感染45例,感染率为17.4%,其中心源性脑栓塞占67%。与对照组相比,急性脑梗塞后肺部感染患者年龄偏高(分别为74.2±13.2和69.8±12.7,P<0.021),住院过程中的误吸(OR5.513)及住院时的NIHSS评分(OR1.090)是独立性危险因素,而肺部感染是加重病情的独立性危险因素(OR5.838)。结论:对于高龄、入院时NIHSS评分高、误吸和心源性急性脑梗塞患者应及早预防,已发生肺部感染者应当给予积极有效的治疗。     

Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

Introduction

Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs.

Objective

To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.

Methods

Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β₂-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002–2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. Outcomes: severe pneumonia (primary) and any pneumonia (secondary).

Results

Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.

Conclusions

The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20–50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.     

老年急性心肌梗死患者并发肺部感染的危险因素分析及护理对策

目的探讨老年急性心肌梗死(AMI)患者并发肺部感染的危险因素及护理对策。方法回顾性分析我院心内科2012年1月~2015年1月收治的老年AMI患者160例的临床资料,根据患者有无并发肺部感染分为感染组(观察组,n=36)和非感染组(对照组,n=124),比较两组患者的性别、年龄、吸烟史、左室射血分数(LVEF)、基础疾病等变量,研究上述变量与肺部感染的相关性,进一步分析AMI患者并发肺部感染的独立危险因素,比较两组患者住院时间和死亡率。结果观察组在年龄、合并糖尿病、吸烟等变量较对照组明显升高,LVEF值较对照组明显下降,差异均有统计学意义(P0.05)。将这些变量纳入多元Logistic回归分析显示,年龄、低EF水平及合并糖尿病是老年AMI患者合并肺部感染的独立危险因素。观察组住院时间为(24.5±2.6)天明显长于对照组的(18.2±3.8)天,病死率为25%明显高于对照组的15.2%,差异均有统计学意义(均P0.05)。结论高龄、低LVEF、合并糖尿病是老年AMI患者并发肺部感染的独立危险因素,对合并上述危险因素患者应实施针对性的护理措施,从而降低老年心梗的病死率。     

Analysis of the Murine Immune Response to Pulmonary Delivery of Precisely Fabricated Nano- and Microscale Particles

Nanomedicine has the potential to transform clinical care in the 21^st century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine''s translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs.     

Specific Features of Neutrophil Response to Chorionic Gonadotropin Related to Sex and the Phase of the Menstrual Cycle

The effect of physiological doses of the main reproductive hormone chorionic gonadotropin (CG) on the functional activity of human neutrophils was studied. The hormone effectively modifies phagocytosis, respiratory burst, and the production of nitrogen oxide by cells. The effects of CG depend on sex and the phase of the menstrual cycle.     

Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

95例SARS患者的Th2细胞因子反应及其临床意义

本研究共收集95例罹患严重急性呼吸综合征（SARS）的医护人员的急性期和恢复期血清,用ELISA方法测定血清中白细胞介素2（IL-2）、白细胞介素4（IL-4）、白细胞介素10（IL-10）、干扰素γ（IFN-γ）、肿瘤坏死因子β（TNF-β）以及转化生长因子β（TGF-β）水平,用流式细胞仪测定急性期患者外周血CD4^＋和CD8^＋T细胞比例。结果显示,SARS患者病程初、中期血清IFN-γ无明显改变;IL-2在起病2月内无显著变化,但在病程3～5个月时降低;IL-4在健康对照和患者均未能测出;TNF-β在SARS感染的1周内和病程第2个月内下降。与上述细胞因子形成对比,患者IL-10以及TGF-β均在发病起即持续升高直至整个病程。这些细胞因子的变化均与激素的使用无关（P〉0．05）。SARS患者急性期CD4^＋T细胞和CD8^＋T细胞急剧减少。可见,SARS相关冠状病毒感染可引起Th2细胞因子反应,可能损害患者的细胞免疫功能而促进体液免疫,IL-10和TGF-β可能在SARS的发病中起作用。     

95例SARS患者的Th2细胞因子反应及其临床意义

本研究共收集95例罹患严重急性呼吸综合征(SARS)的医护人员的急性期和恢复期血清,用ELISA方法测定血清中白细胞介素2(IL-2)、白细胞介素4(IL-4)、白细胞介素10(IL-10)、干扰素γ(IFN-γ)、肿瘤坏死因子β(TNF β)以及转化生长因子β(TGF-β)水平,用流式细胞仪测定急性期患者外周血CD4+和CD8+T细胞比例.结果显示,SARS患者病程初、中期血清IFN-γ无明显改变;IL-2在起病2月内无显著变化,但在病程3～5个月时降低;IL-4在健康对照和患者均未能测出;TNF-β在SARS感染的1周内和病程第2个月内下降.与上述细胞因子形成对比,患者IL-10以及TGF-β均在发病起即持续升高直至整个病程.这些细胞因子的变化均与激素的使用无关(P＞0.05).SARS患者急性期CD4+T细胞和CD8+T细胞急剧减少.可见,SARS相关冠状病毒感染可引起Th2细胞因子反应,可能损害患者的细胞免疫功能而促进体液免疫,IL-10和TGF-β可能在SARS的发病中起作用.     

Zinc Regulates the Acute Phase Response and Serum Amyloid A Production in Response to Sepsis through JAK-STAT3 Signaling

Sepsis rapidly activates the host inflammatory response and acute phase response. Severe sepsis, complicated by multiple organ failure, is associated with overwhelming inflammation and high mortality. We previously observed that zinc (Zn) deficiency significantly increases mortality in a mouse model of polymicrobial sepsis due to over-activation of the inflammatory response. In order to identify potential mechanisms that account for Zn-responsive effects, we generated whole exome expression profiles from the lung tissue of septic mice that were maintained on Zn modified diets. Based on systems analysis, we observed that Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production. In vitro studies of primary hepatocytes and HepG2 cells substantiated that Zn-deficiency augments serum amyloid A production through up-regulation of the JAK-STAT3 and NF-κB pathways. In contrast, Zn inhibited STAT3 activation through the up-regulation of SHP1 activity. Collectively, these findings demonstrate that Zn deficiency enhances the acute phase response through up-regulation of the JAK-STAT3 pathway, thereby perpetuating increased inflammation that may lead to increased morbidity and mortality in response to sepsis.     

Linking Lysosomal Trafficking Defects with Changes in Aging and Stress Response in Drosophila

Defects in pathways that direct cellular components to the lysosome for degradation are often linked with a decrease in viability and with progressive disorders. Previously we had shown that blue cheese (bchs: Drosophila homologue of human Alfy) mutations lead to reduced longevity and the accumulation of ubiquitinated neural aggregates. A genetic modifier screen based on overexpression of Bchs in the eye was used to identify several potential genetic interactions, which included autophagic and endocytic trafficking genes as well as cytoskeletal and motor proteins and members of the SUMO and ubiquitin signaling pathways. We found that mutations in several of the genes identified in the screen also result in bchs-like phenotypes, including a reduction in adult lifespan and changes in ubiquitinated protein profiles. In addition, we show that Bchs modifiers belonging to the autophagic and trans-Golgi trafficking pathways also display defects in adult starvation response. Our data further support a role for Bchs/Alfy in the autophagic pathway and strongly indicate that autophagy plays an important role in aging and stress response.

Addendum to:

Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport with Decreased Lifespan and Altered Ubiquitinated Protein Profiles

A. Simonsen, R. Cumming, K. Lindmo, V. Galaviz, S. Cheng, T. Rusten and K. Finley

Genetics 2007; In press     

Potentiated Interaction between Ineffective Doses of Budesonide and Formoterol to Control the Inhaled Cadmium-Induced Up-Regulation of Metalloproteinases and Acute Pulmonary Inflammation in Rats

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases.     

Risk of Hospitalization for Acute Cardiovascular Events among Subjects with Lower Urinary Tract Symptoms: A Nationwide Population-Based Study

Background and Purpose

Lower urinary tract symptoms (LUTS) have been reported to be associated with metabolic syndrome and may predispose subjects to cardiovascular disease. The magnitude of the impact on the medical care remains to be elucidated. Based on a population-based claims dataset in Taiwan, we explored the association between LUTS and the risk of subsequent hospitalization for acute cardiovascular events.

Materials and Methods

Among a representative sample of one million subjects from nationwide health insurance enrollees, subjects with codes of LUTS in service claims and without previous cardiovascular diseases including stroke were compared with age- and sex-matched non-LUTS subjects in subsequent hospitalization for acute coronary syndrome or stroke from the recruited date (between 2001–2004) to 2009. The risk of outcomes was assessed with Kaplan-Meier curves and the impact of LUTS was estimated with Poison regression analysis and Cox proportional hazards models.

Results

We included 4,553 LUTS subjects and 22,765 matched non-LUTS subjects, with a mean age of 47 years and 43% of men. Hypertension, diabetes, and hyperlipidemia were more prevalent in the LUTS group. The incidence rate of the composite endpoint was significantly higher in the LUTS group than in the non-LUTS group (5.4/1000 vs. 4.0/1000 person-years). The difference mainly derived from stroke rather than acute coronary syndrome. After adjusting for age, sex, diabetes, hypertension, and hyperlipidemia in multivariable analysis, LUTS remained a significant predictor (hazard ratio, 1.29; 95% confidence incidence, 1.06–1.50).

Conclusion

Subjects free of cardiovascular disease and presenting with LUTS are at risk of subsequent hospitalization for acute cardiovascular events, mainly stroke. The information might prompt practitioners encountering such patients to undergo appropriate diagnostic and preventive measures.     

老年急性呼吸窘迫综合征肺内及肺外源性危险因素分析

目的:探讨老年急性呼吸窘迫综合征肺内及肺外源性危险因素。方法:回顾性分析130例老年ARDS患者,对其中的肺内及肺外源性危险因素进行分析。结果:肺内源性ARDS病因以误吸和肺炎为主,而肺外源性ARDS则以脓毒血症、大手术后等为主;在死亡上均与多器官功能障碍综合征、呼吸衰竭为主要因素,且两组死亡率接近。结论:在老年急性呼吸窘迫综合征中,肺外源性在器官功能衰竭和氧合指数上重于肺内源性,但是在其他因素和死亡结局上均无明显差异性。