Systemic inflammation in COPD visualised by gene profiling in peripheral blood neutrophils

Background: The inflammatory process in chronic obstructive pulmonary disease (COPD) is characterised by the presence of neutrophils in the lung that are able to synthesise de novo several inflammatory mediators. The local chronic persistent inflammatory response is accompanied by systemic effects such as cytokine induced priming of peripheral leucocytes and muscle wasting. The preactivation or priming of peripheral blood neutrophils was used to gain more insight into the mechanisms of this systemic inflammatory response.

Methods: Gene arrays were performed on peripheral blood neutrophils obtained from healthy donors after stimulation in vitro with tumour necrosis factor (TNF)-α, granulocyte-macrophage colony stimulating factor (GM-CSF), or both. The expression of many inflammatory genes was regulated in these cells following stimulation. The expression of inflammatory genes in peripheral blood neutrophils in healthy subjects and those with COPD was measured by real time RT-PCR after stimulation with TNFα, GM-CSF, interleukin (IL)-8, fMLP, TNFα + GM-CSF, and lipopolysaccharide (LPS).

Results: The genes regulated in the gene array with TNFα/GM-CSF stimulated neutrophils included cytokines (such as IL-1ß), chemokines (such as IL-8), and adhesion molecules (such as ICAM-1). Disease severity as measured by forced expiratory volume in 1 second (FEV₁) in COPD patients correlated with expression of several of these genes including IL-1ß (r = –0.540; p = 0.008), MIP-1ß (r = –0.583; p = 0.003), CD83 (r = –0.514; p = 0.012), IL-1 receptor 2 (r = –0.546; p = 0.007), and IL-1 receptor antagonist (r = –0.612; p = 0.002).

Conclusions: These data are consistent with the hypothesis that progression of COPD is associated with the activation of neutrophils in the systemic compartment. De novo expression of inflammatory mediators by peripheral blood neutrophils suggests a pro-inflammatory role for these cells in the pathogenesis of COPD.

     

Single-step maternal serum screening for trisomy 21 in the era of combined or integrated screening

Single-step maternal serum screening (MSS) in the first (1MSS) or second (2MSS) trimester at maternal age > or =35 years was evaluated in the North Belgian region Flanders, where difficulties are encountered in the general introduction of combined or integrated screening algorithms. The fetal aneuploidy screening database of General Medical Laboratory AML in Antwerp was searched for 2MSS tests between 1992 and 1999 (alpha-fetoprotein, beta-human chorionic gonadotropin (beta-HCG) and unconjugated estriol, cut-off 1:300) and for 1MSS tests between 1999 and 2003 (free beta-HCG and pregnancy-associated plasma protein A, cut-off 1:85). At > or =35 years, the detection rate for trisomy 21 (DR) was 93.8% (15/16) for 2MSS and the screen-positive rate (SPR) was 24.5% (504/2061). For 1MSS, these figures were 85.7% (6/7) and 17.7% (109/615) respectively. To detect one trisomy 21, missed by MSS at > or =35 years of age, an additional number of 1,557 and 506 primary invasive procedures would be needed for 2MMS and 1MSS respectively. We conclude that the performance of both single-step 1MSS and 2MSS at maternal age > or =35 years in Flanders is excellent, even without the combination with ultrasound parameters or integration of first and second trimester parameters. The simplicity of both methods allows to consider them valuable options for fetal aneuploidy screening at advanced maternal age, until high quality combined or integrated screening is accessible to all pregnant women in Belgium.     

Leptin in Morbidly Obese Patients: No Role for Treatment of Morbid Obesity but Important in the Postoperative Immune Response

Despite the current opinion that leptin can no longer be seen as a hormone which could be used therapeutically to prevent an energy surplus (it rather protects the organism for an energy deficit), leptin may still have an impact in clinical medicine. Leptin was shown to have several important functions. The pleiotropic properties of leptin include a regulatory function in the immune system. Reviewing the effects of leptin on different parts of the immune system reveals that the immune system is deregulated in an environment low in leptin. A strong reduction in leptin levels occurs in situations of starvation as seen after bariatric surgery. We postulate the hypothesis that the starvation-induced postoperative decrease of leptin is causative of the more serious course of complications observed after bariatric surgery.     

Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction

Context  The role of estrogens in ischemic heart disease (IHD) is uncertain. Evidence suggests that genetic variations in the estrogen receptor (ESR1) gene may influence IHD risk, but the role of common sequence variations in the ESR1 gene is unclear. Objective  To determine whether the ESR1 haplotype created by the c.454-397T>C (PvuII) and c.454-351A>G (XbaI) polymorphisms is associated with myocardial infarction (MI) and IHD risk. Design, Setting, and Participants  In 2617 men and 3791 postmenopausal women from The Rotterdam Study (enrollment between 1989-1993 and follow-up to January 2000), a population-based, prospective cohort study of participants aged 55 years and older, ESR1 c.454-397T>C and c.454-351A>G haplotypes were determined. Detailed interviews and physical examinations were performed, blood samples were obtained, and cardiovascular risk factors were assessed. Main Outcome Measure  The primary outcome was MI and IHD defined as MIs, revascularization procedures, and IHD mortality. Results  Approximately 29% of women and 28.2% of men were homozygous carriers of the ESR1 haplotype 1 (–397 T and –351 A) allele, 49% of women and 50% of men were heterozygous carriers, and 22% of women and 21.4% of men were noncarriers. During a mean follow-up of 7.0 years, 285 participants (115 women; 170 men) had MI, and 440 (168 women; 272 men) had an IHD event, of which 97 were fatal. After adjustment for known cardiovascular risk factors, female heterozygous carriers of haplotype 1 had an increased risk of MI (event rate, 2.8%; relative risk [RR], 2.23; 95% confidence interval [CI], 1.13-4.43) compared with noncarriers (event rate, 1.3%), whereas homozygous carriers had an increased risk (event rate, 3.2%; RR, 2.48; 95% CI, 1.22-5.03). For IHD events, we observed a similar association. In women, the effect of haplotype 1 on fatal IHD was larger than on nonfatal IHD. In men, the ESR1 haplotypes were not associated with an increased risk of MI (event rate, 5.7%; RR, 0.93; 95% CI, 0.59-1.46 for heterozygous carriers; and event rate, 5.1%; RR, 0.82; 95% CI, 0.49-1.38 for homozygous carriers) compared with noncarriers (event rate, 5.8%) and were not associated with an increased risk of IHD. Conclusions  In this population-based, prospective cohort study, postmenopausal women who carry ESR1 haplotype 1 (c.454-397 T allele and c.454-351 A allele) have an increased risk of MI and IHD, independent of known cardiovascular risk factors. In men, no association was observed.      

Impact of worktime arrangements on work-home interference among Dutch employees

OBJECTIVES: This study examined the effects of different worktime arrangements on work-home interference while taking into account other work-related factors, private situation and health status, explored gender differences in this relation, and examined reciprocal effects between workhours and work-home interference. METHODS: Data from the Maastricht cohort study on fatigue at work were used with 8 months of follow-up (N=6947 at baseline). RESULTS: Worktime arrangements were related to work-home interference among the men and women, even after control for confounding. As compared with daywork, baseline shiftwork was associated with higher work-home interference over time. Within daywork, full-time work was prospectively related to higher work-home interference than part-time work was. For full-timers, baseline overtime work, hours of overtime work, change in number of workhours, and commuting time were related to higher work-home interference over time, whereas compensation for overtime work, familiarity with work roster, ability to take a day off, and a decrease in workhours at own request were associated with less work-home interference. For the part-timers, baseline overtime work and commuting time were related to higher work-home interference over time, whereas compensation for overtime, flexible workhours, and ability to take a day off were protective against work-home interference. Reciprocal relations between work-home interference and workhours were also found. CONCLUSIONS: Worktime arrangements are clearly related to work-home interference. Because reciprocal effects exist as well, important selection processes may exist. Nevertheless, specific characteristics of worktime arrangements could constitute useful tools for reducing work-home interference.     

1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery

The purpose of the study was to investigate the sequence of processes occurring during and after hypoxia-induced acidemia. We used proton nuclear magnetic resonance spectroscopy, which provides an overview of metabolites in cerebrospinal fluid (CSF), reflecting neuronal metabolism and damage. The pathophysiological condition of acute fetal asphyxia was mimicked by reducing maternal uterine blood flow in 14 unanesthetized pregnant ewes. CSF metabolites were measured during hypoxia-induced acidemia, and during the following recovery period, including the periods at 24 and 48 h after the hypoxic insult. Maximum values of the following CSF metabolites were reached during severe hypoxia (pH 相似文献