Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

BACKGROUND: Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF) has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs). Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6) and the chemokines, monocyte chemoattractant protein (Mcp-1), macrophage inflammatory protein-2 (Mip-2) and keratinocyte derived chemokine (Kc) in the lung tissue at different time points after exposure. RESULTS: Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. CONCLUSION: Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

<p>Abstract</p> <p>Background</p> <p>A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, <it>ERCC1</it>, <it>ERCC2</it>, and <it>PPP1R13L </it>(aka <it>RAI</it>) are related to DNA repair and cell survival, and one, <it>CD3EAP</it>, aka <it>ASE1</it>, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers.</p> <p>Methods</p> <p>We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk.</p> <p>Results</p> <p>We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the F_stvalue) closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping.</p> <p>Conclusion</p> <p>The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.</p

Determinants of the range of drugs prescribed in general practice: a cross-sectional analysis

Background: Current health policies assume that prescribing is more efficient and rational when general practitioners (GPs) work with a formulary or restricted drugs lists and thus with a limited range of drugs. Therefore we studied determinants of the range of drugs prescribed by general practitioners, distinguishing general GP-characteristics, characteristics of the practice setting, characteristics of the patient population and information sources used by GPs. Methods: Secondary analysis was carried out on data from the Second Dutch Survey in General Practice. Data were available for 138 GPs working in 93 practices. ATC-coded prescription data from electronic medical records, census data and data from GP/ practice questionnaires were analyzed with multilevel techniques. Results: The average GP writes prescriptions for 233 different drugs, i.e. 30% of the available drugs on the market within one year. There is considerable variation between ATC main groups and subgroups and between GPs. GPs with larger patient lists, GPs with higher prescribing volumes and GPs who frequently receive representatives from the pharmaceutical industry have a broader range when controlled for other variables. Conclusion: The range of drugs prescribed is a useful instrument for analysing GPs' prescribing behaviour. It shows both variation between GPs and between therapeutic groups. Statistically significant relationships found were in line with the hypotheses formulated, like the one concerning the influence of the industry. Further research should be done into the relationship between the range and quality of prescribing and the reasons why some GPs prescribe a greater number of different drugs than others.

Phenotypic Plasticity and Contemporary Evolution in Introduced Populations: Evidence from Translocated Populations of White Sands Pupfish (Cyrpinodon tularosa)

Contemporary evolution has been shown in a few studies to be an important component of colonization ability, but seldom have researchers considered whether phenotypic plasticity facilitates directional evolution from the invasion event. In the current study, we evaluated body shape divergence of the New Mexico State-threatened White Sands pupfish (Cyprinodon tularosa) that were introduced to brackish, lacustrine habitats at two different time in the recent past (approximately 30 years and 1 year previously) from the same source population (saline river environment). Pupfish body shape is correlated with environmental salinity: fish from saline habitats are characterized by slender body shapes, whereas fish from fresher, yet brackish springs are deep-bodied. In this study, lacustrine populations consisted of an approximately 30-year old population and several 1-year old populations, all introduced from the same source. The body shape divergence of the 30-year old population was significant and greater than any of the divergences of the 1-year old populations (which were for the most part not significant). Nonetheless, all body shape changes exhibited body deepening in less saline environments. We conclude that phenotypic plasticity potentially facilitates directional evolution of body deepening for introduced pupfish populations

The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms

Many parasitic infections, including those of humans, are caused by complex lifecycle parasites (CLPs): parasites that sequentially infect different hosts over the course of their lifecycle. CLPs come from a wide range of taxonomic groups-from single-celled bacteria to multicellular flatworms-yet share many common features in their life histories. Theory tells us when CLPs should be favoured by selection, but more empirical studies are required in order to quantify the costs and benefits of having a complex lifecycle, especially in parasites that facultatively vary their lifecycle complexity. In this article, we identify ecological conditions that favour CLPs over their simple lifecycle counterparts and highlight how a complex lifecycle can alter transmission rate and trade-offs between growth and reproduction. We show that CLPs participate in dynamic host-parasite coevolution, as more mobile hosts can fuel CLP adaptation to less mobile hosts. Then, we argue that a more general understanding of the evolutionary ecology of CLPs is essential for the development of effective frameworks to manage the many diseases they cause. More research is needed identifying the genetics of infection mechanisms used by CLPs, particularly into the role of gene duplication and neofunctionalisation in lifecycle evolution. We propose that testing for signatures of selection in infection genes will reveal much about how and when complex lifecycles evolved, and will help quantify complex patterns of coevolution between CLPs and their various hosts. Finally, we emphasise four key areas where new research approaches will provide fertile opportunities to advance this field

Outcomes of Brood Parasite–Host Interactions Mediated by Egg Matching: Common Cuckoos Cuculus canorus versus Fringilla Finches

Antagonistic species often interact via matching of phenotypes, and interactions between brood parasitic common cuckoos (Cuculus canorus) and their hosts constitute classic examples. The outcome of a parasitic event is often determined by the match between host and cuckoo eggs, giving rise to potentially strong associations between fitness and egg phenotype. Yet, empirical efforts aiming to document and understand the resulting evolutionary outcomes are in short supply.We used avian color space models to analyze patterns of egg color variation within and between the cuckoo and two closely related hosts, the nomadic brambling (Fringilla montifringilla) and the site fidelic chaffinch (F. coelebs). We found that there is pronounced opportunity for disruptive selection on brambling egg coloration. The corresponding cuckoo host race has evolved egg colors that maximize fitness in both sympatric and allopatric brambling populations. By contrast, the chaffinch has a more bimodal egg color distribution consistent with the evolutionary direction predicted for the brambling. Whereas the brambling and its cuckoo host race show little geographical variation in their egg color distributions, the chaffinch's distribution becomes increasingly dissimilar to the brambling's distribution towards the core area of the brambling cuckoo host race.High rates of brambling gene flow is likely to cool down coevolutionary hot spots by cancelling out the selection imposed by a patchily distributed cuckoo host race, thereby promoting a matching equilibrium. By contrast, the site fidelic chaffinch is more likely to respond to selection from adapting cuckoos, resulting in a markedly more bimodal egg color distribution. The geographic variation in the chaffinch's egg color distribution could reflect a historical gradient in parasitism pressure. Finally, marked cuckoo egg polymorphisms are unlikely to evolve in these systems unless the hosts evolve even more exquisite egg recognition capabilities than currently possessed