1,721,020 research outputs found
Endothelial Cell-Immune Cell Interaction in IBD
No full textThe proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells. (C) 2016 S. Karger AG, Base
Platelet activation and the CD40/CD40 ligand pathway: Mechanisms and implications for human disease
No full textThe discovery that platelets express CD40 and the CD40 ligand has transformed these cells, once seen as exclusively involved in coagulation and thrombosis, into active players of immunity and inflammatory injury. Many of the broad and potent biological activities mediated through the CD40/CD40 pathway by immune and nonimmune cells are also exerted by activated platelets. This occurs either through the constitutive expression of CD40 on the platelet surface or the activation-induced expression of the CD40 ligand, which is membrane bound and released from the surface in a soluble form. The most prominent activities mediated by the platelet CD40/CD40 ligand pathway include inflammatory, immunoregulatory, and hemostatic functions, all of which contribute to the newly expanded view of platelets as key biological mediators involved in disease processes such as atherosclerosis, inflammatory bowel disease, and diabetes. Therefore, considering platelet CD40 and CD40 ligand as novel biological targets is justified and supported by animal studies. The clinical profit to be gained from blocking this molecular pair will be determined by results in humans with conditions in which the platelet CD40/CD40 ligand pathway is crucially involved in disease pathogenesis
Immune regulation by microvascular endothelial cells: Directing innate and adaptive immunity, coagulation, and inflammation
No full textAn effective immune response depends not only on the proper activation, regulation, and function of immune cells, hut also on their distribution and retention in diverse tissue mi. croenvironments where they encounter a number of stimuli and other cell types. These activities are mediated by endiothelial cells, which form specialized microcirculatory networks used by immune cells under both physiological and pathological circumstances. Endothelial cells represent a highly heterogeneous population of cells with the ability to interact with and modulate the function of immune cells. This review is focused on the role of microvascular endothelial cells in innate and adaptive immunity, inflammation, coagulation, angiogenesis, and the therapeutic implications of targeting endothelial cells in selected autoimmune and chronic inflammatory disorders. The Journal of Immunology, 2007, 178: 6017-6022
Inflammatory bowel disease: the role of environmental factors
No full textEnvironmental factors are essential components of the pathogenesis of inflammatory bowel disease (IBD) and primarily responsible for its growing incidence around the globe. Epidemiological, clinical and experimental evidence support an association between IBD and a large number of seemingly unrelated environmental factors, which include smoking, diet, drugs, geographical and social status, stress, microbial agents, intestinal permeability and appendectomy. Data supporting the involvement of each of these factors in predisposing to, triggering, or modulating the course or outcome of IBD vary from strong to tenuous. Smoking and the enteric bacterial flora are the ones for which the most solid evidence is currently available. Smoking increases the risk of Crohn's disease (CD) and worsens its clinical course, but has a protective effect in ulcerative colitis (UC). Presence of enteric bacteria is indispensable to develop gut inflammation in most animal models of IBD, and modulation of the quantity or quality of the flora can be beneficial in patients with IBD. Surprisingly, evidence for a major role of the diet in inducing or modifying IBD is limited, while that for nonsteroidal anti-inflammatory drugs is more convincing than for oral contraceptives. Northern geographic location, and a high social, economical, educational or occupational status increase the risk of IBD, an observation fitting the hygiene hypothesis for allergic and autoininume diseases. Stress is also associated with IBD, but more as a modifier than an inducing factor, and its contribution is more obvious in IBD animal models than human IBD. Finally, an increased intestinal permeability may increase the risk for developing CD, whereas an appendectomy lowers the risk of developing UC. (C) 2004 Elsevier B.V All rights reserved
Mechanical Response of Ni-Based CU5MCuC Alloy to Different Stabilization Thermal Treatments
Full text linkThe Ni–Fe–Cr system is the basis of a series of commercial alloys featuring chemical–physical characteristics that allow them to be used in a variety of fields where excellent resistance to aggressive environments is required. In this scenario, the CU5MCuC alloy, the foundry counterpart of Alloy 825, is proving successful in the petrochemical field thanks to its good corrosion resistance in acidic and highly oxidizing environments. Intergranular corrosion resistance, critical for this material, is ensured by the stabilization treatment that allows precipitation of Nb carbides. Strengthening of this alloy takes place only via a solid solution. Therefore, its mechanical properties depend on the solution annealing treatment: often this treatment alone does not make it possible to reach the UTS imposed by the ASTM-A494 standard. In this work, the possibility of using stabilization treatment to increase mechanical strength as well was considered. Treatments, with different combinations of time and temperature, were carried out in order to modify the material’s microstructure. After the thermal treatments, microstructural analyses, mechanical tests and (pitting and intergranular) corrosion and resistance tests were carried out to identify optimal treatment parameters in order to promote the evolution of microstructural constituents capable of improving mechanical strength without decreasing corrosion resistance. The treatment that achieves the best compromise between mechanical properties and corrosion resistance is stabilization at 970 °C for 4 h
Late-breaking news from the "4th International Meeting on Inflammatory Bowel Diseases" Capri, 2006. Inflamm Bowel Dis. 2007;13:1031-1050
No full textAt the "4th International Meeting on Inflammatory Bowel Diseases: on the Way to
New Therapies," Capri, 2006, genetics, bacteria-host interactions,
immunomodulation, and tissue response were discussed deeply in order to
understand, rationalize, and develop novel therapies. About genetics, the
importance of a better understanding of the nature of known loci and of the
putative associations was stressed. It was confirmed that genotype-phenotype
associations in inflammatory bowel disease (IBD) have important clinical and
therapeutic implications. The importance of the search for dominant bacterial
antigens in chronic immune-mediated intestinal inflammation emerged, as well as
knowledge of cellular and molecular mechanisms of bacterial-host interactions. It
was discussed how innate and adaptive immunity signaling events can perpetuate
chronic inflammation. Signal transduction pathways provide an intracellular
mechanism by which cells respond and adapt to environmental stress. The
identification of these signals have led to a greater understanding of the
pathogenesis of IBD and pointed to potential therapeutic targets. It was shown
that immune homeostasis is lost in IBD, resulting in a complex tissue response
involving the action of immune and nonimmune cells. The nonimmune tissue response
in IBD could be regarded as a new target for control of chronic intestinal
inflammation. The changing role of biotherapy in IBD was widely discussed and in
particular the anti-TNF-alpha monoclonal antibodies. Granulocyte-colony
stimulating factor (GM-CSF) and stem cells therapies were also discussed. The
risk-to-benefit ratio of the novel therapies was analyzed in detail. Finally,
future directions for basic science and the unmet needs for clinical practice
were presented
News from the "5th International Meeting on Inflammatory Bowel Diseases" CAPRI 2010.
No full textAbstract
At the “5th International Meeting on Inflammatory Bowel Diseases selected topics of inflammatory
bowel disease (IBD), including the environment, genetics, the gut flora, the cell response and
immunomodulation were discussed in order to better understand specific clinical and therapeutic
aspects. The incidence of IBD continues to rise, both in lowand in high-incidence areas. It is believed
that factors associated with ‘Westernization’may be conditioning the expression of these disorders.
The increased incidence of IBD among migrants from low-incidence to high-incidence areas within
the same generation suggests a strong environmental influence.
The development of genome-wide association scanning (GWAS) technologies has lead to the
discovery of more than 100 IBD loci. Some, as the Th 17 pathway genes, are shared between
Crohn's disease (CD) and ulcerative colitis (UC), while other are IBD subtype-specific (autophagy
genes, epithelial barrier genes). Disease-specific therapies targeting these pathways should be
developed. Epigenetic regulation of the inflammatory response also appears to play an important
role in the pathogenesis of IBD.
The importance of gut flora in intestinal homeostasis and inflammation was reinforced, the
concepts of eubiosis and dysbiosis were introduced, and some strategies for reverting dysbiosis to
a homeostatic state of eubiosis were proposed. The current status of studies on the human gut
microbiota metagenome, metaprotome, and metabolome was also presented.
The cell response in inflammation, including endoplasmic reticulum (ER) stress responses,
autophagy and inflammasome-dependent events were related to IBD pathogenesis. It was
suggested that inflammation-associated ER stress responses may be a common trait in the
pathogenesis of various chronic immune and metabolic diseases.
How innate and adaptive immunity signaling events can perpetuate chronic inflammation was
discussed extensively. Signal transduction pathways provide intracellular mechanisms by which
cells respond and adapt to multiple environmental stresses. The identification of these signals
has led to a greater mechanistic understanding of IBD pathogenesis and pointed to potentially
new therapeutic targets.
A critical analysis of clinical trials and of risk-benefit of biological therapy was presented. The
problem of Epstein–Barr virus (EBV) and lymphoma in IBD was extensively discussed. Lymphomas
can develop in intestinal segments affected by IBD and are in most cases associated with EBV. The
reasons of treatment failure were also analyzed both from basic and clinical points of view.
Two very interesting presentations on the integration of research and clinical care in the near
future closed the meeting. These presentations were focused on macrotrends affecting
healthcare delivery and research, and the need to innovate traditional infrastructures to deal
with these changing trends as well as new opportunities to accelerate scientific knowledge
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