Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to ...evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs). Thirty HDM-AAs and ten healthy persons (HCs)were recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp) and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0) and 24 hours (T24) after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 ± 96 pg/ml) and PAI-1 (4341 ± 1262 pg/ml) concentrations were higher than in HC (18.8 ± 6.7 pg/ml; p=0.0002 and 596 ± 180 pg/ml; p<0.0001; for uPA and PAI-1 respectively). After allergen challenge further increase in sputum uPA (187 ± 144 pg/ml; p=0.03) and PAI-1 (6252 ± 2323 pg/ml; p<0.0001) concentrations were observed. Moreover, in Dp challenged, but not in saline challenged HDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters were found in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways. Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodeling and play an important role in the development of bronchial hyperreactivity.
•Mitochondrial DNA (mtDNA) alterations are associate with canine development of diseases.•Mitochondrial diseases are highly heterogenic conditions induced by many factors.•The majority of mtDNA ...defects are canine mitochondrial myopathies, encephalopathies, and tumours.•More attention should be paid to the proper diagnosis of animals suffering from mitochondrial diseases.•There is a need to develop reliable molecular testing to confirm unambiguously the cause of development of canine mitochondrial diseases.
Currently, the issue of the aetiology of mitochondrial diseases resulting from mitochondrial DNA (mtDNA) defects is underestimated. Genetic research is mostly focused on alterations in the nuclear genome (nDNA), and its impact on disease development as well as further health consequences without considering mtDNA abnormalities. However, in the case of energy-dependent diseases, it is important to understand the bioenergetic pathophysiology and its relation with mtDNA changes.
In the current animal research, there is limited data about mtDNA defects and their association with the development of bioenergetic diseases in the domestic dog (Canis lupus familiaris) in contrast to human medicine, where mitochondrial genetics research has recently increased. Molecular findings about mtDNA indicate that improper functioning of mitochondria resulting from genetic defects of mtDNA has a severe impact on cells and tissues, especially those that are heavily dependent on oxidative metabolism such as the brain, skeletal and cardiac muscles and, consequently, the whole organism.
The aim of this paper is to highlight the role of defects of mitochondria and mtDNA on the development and course of different diseases in the domestic dog. The field of canine mitochondrial genetics and genomics is definitely inexhaustible and it is worth drawing attention to the importance and consequences of the mitochondrial genome alterations. This review collects scientific data on mitochondrial DNA with special regard to the structure, features of canine mtDNA, and abnormalities in the mitochondrial genome and their association with the course and development of diseases, including mitochondrial myopathies, encephalopathies, and tumours.
Purpose
Statistics shows terrifying tendencies in people’ unwillingness to develop themselves by reading books. The situation is even more serious if we look at companies and their employees. People ...want to be specialists, but in fact reading culture in companies is rare. Many actions which are undertaken to reverse this trend may lead to sales increase of books by collecting them instead of reading them, if the quality of handbooks will not be improved. To enhance people to read, it is essential to offer them a product that would really satisfy their needs. The study presented in the paper contributes to the knowledge about some general practitioners requirements for handbooks on methods, in particular these used in quality and management. It shows also the usefulness of Kano’s model application in the new area. A case study was conducted with the application of Kano’s model to identify potential readers’ expectations of a handbook for practitioners in problem-solving methods. The research was based on sample size equal to 376 different people: managers, specialists, operators, directors, students and professors in Poland. As a result, a book on problem solving method called “5 why” was created to verify if the model really works.
Design/methodology/approach
It shows the usefulness of Kano’s model application in the new area of education.
Findings
Potential readers’ expectations of a handbook for practitioners in problem solving methods were identified. The research was based on sample size equal to 376 different people: managers, specialists, operators, directors, students and professors in Poland.
Social implications
By taking into consideration expectations from customers, authors of books and educational services may improve their works. Both sides would make profits form this: customers – better product, authors – bigger and satisfied audience.
Originality/value
From many previous researches, it is known that the Kano’s model is a useful, practical tool for industries; however, studies show that it is also well applicable in providing education service. As a result of the research, a book on problem-solving method called “5 why” was created to prove if the model really works in practice.
Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust ...mite allergic asthmatics (HDM-AAs). The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs). Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml) and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml) were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively). The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001) and with logarithmically transformed exhaled nitric oxide concentration (eNO) (r=0.486; p=0.035) but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005) and bronchial reactivity to histamine expressed as log(PC20) (r=-0.824; p<0.0001) but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.
The -675 4G/5G plasminogen activator inhibitor-1 (PAI-1) polymorphism is linked with asthma and bronchial hyperreactivity. The aim of this study was to evaluate the effect of allergen challenge on ...plasma PAI-1 concentration in relation to the -675 4G/5G PAI-1 gene polymorphism in house dust mite-allergic asthma patients (HDM-AAs).
The study was performed in 54 HDM-AAs and 54 healthy nonatopic controls (HCs). Plasma samples were collected in HDM-AAs before, as well as 30 min, 6 h and 24 h after allergen challenge and at corresponding time points in sham-challenged HCs.
In subjects carrying the individual PAI-1 genotype, the mean baseline plasma PAI-1 concentration was greater in HDM-AAs than in HCs. At 30 min the mean increase in plasma PAI-1 concentration was significantly greater in HDM-AAs (14.4 +/- 12.9 ng/ml) than in HCs (3.4 +/- 3.2 ng/ml; p < 0.001). At 6 h, plasma PAI-1 concentration greater than before challenge was found in only 4 HCs (7.4%) but in 48 HDM-AAs (88.9%; p < 0.0001). An increase in plasma PAI-1 concentration at 6 h was found in all HDM-AAs carrying the 4G allele but only in 33.3% of the 5G homozygotes (p < 0.0001). The strongest correlation was found between log PC20 and PAI-1 plasma concentration over the period of 24 h (r = -0.507; p = 0.0001).
Changes in plasma PAI-1 concentration associated with allergen-induced bronchoconstriction are modulated by the -675 4G/5G polymorphism of the PAI-1 gene. Allergen-induced upregulation of PAI-1 synthesis may participate in the development of bronchial hyperreactivity in HDM-AAs.
Timothy grass pollen is a source of potent allergens. Among them, Phl p 1 and Phl p 5 are thought to be the most important, as a majority of timothy grass-allergic individuals have IgE antibodies ...directed against these two allergens. The profilin from timothy grass (Phl p 12) has been registered as a minor allergen, with up to 35% of individuals in populations of grass pollen allergic patients showing IgE binding to Phl p 12. Profilins are primarily minor allergens and are known for a high likelihood of co-sensitization as well as cross-reactivity situations caused by their sequence and structure similarity. The crystal structure of Phl p 12.0101 was determined and it revealed that this allergen may form an unusual dimer not previously observed among any profilins. For example, the Phl p 12 dimer has a completely different geometry and interface when compared with the latex profilin (Hev b 8) dimer that has its crystal structure determined. The structure of Phl p 12.0101 is described in the context of allergenic sensitization and allergy diagnostics. Moreover, the structure of the Phl p 12.0101 dimer is discussed, taking into account the production of recombinant allergens and their storage.
CD163 and its role in inflammation Kowal, Krzysztof; Silver, Richard; Sławińska, Emila ...
Folia histochemica et cytobiologica,
01/2011, Letnik:
49, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific ...marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response.
Abstract
Objectives
This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry ...mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients.
Methods
Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects.
Results
Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud’s phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT.
Conclusion
These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.
Phenotypes/endotypes-driven treatment in asthma Braido, Fulvio; Tiotiu, Angelica; Kowal, Krzysztof ...
Current opinion in allergy and clinical immunology,
2018-June, 2018-06-00, 20180601, Letnik:
18, Številka:
3
Journal Article
PURPOSE OF REVIEWTarget therapy is the necessary step towards personalized medicine. The definition of asthma phenotypes and underlying mechanisms (endotypes) represent a key point in the development ...of new asthma treatments. Big data analysis, biomarker research and the availability of monoclonal antibodies, targeting specific cytokines is leading to the rapid evolution of knowledge. In this review, we sought to outline many of the recent advances in the field.
RECENT FINDINGSSeveral attempts have been made to identify asthma phenotypes, sometimes with contrasting results. More success has been obtained concerning the pathogenetic mechanism of specific asthma patterns with the consequent identification of biomarkers and development of effective ad hoc treatment.
SUMMARYWe are in the middle of an extraordinary revolution of our mode of thinking about and approaching asthma. All the effort in the identification of clusters of patients with different disease clinical patterns, prognosis and response to treatment is closely linked to the identification of endotypes (Th2-low and Th2-high). This approach has allowed the development of the specific treatments (anti IgE, Anti IL5 and IL5R) that are now available and is leading to new ones.
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