Learning the Language

pages 30-3

Cysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. Methods: Twenty-two patients (11 corticosteroid free, mean FEV1 99% predicted, 11 corticosteroid-treated, mean FEV1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. Results: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 +/- 42 pg/ml) and steroid-treated (228 +/- 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 +/- 0.22) and corticosteroid-treated (2.98 +/- 0.35) asthmatics. Montelukast (100 mu M) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 +/- 9.2% (P < 0.001) and 64.7 +/- 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. Conclusion: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids.Peer reviewe

Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis

BACKGROUND: Prostanoids are known to participate in the process of fibrogenesis. Because lung fibroblasts produce prostanoids and are believed to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), we hypothesized that fibroblasts (HF) cultured from the lungs of patients with IPF (HF-IPF) have an altered balance between profibrotic (thromboxane [TX]A(2)) and antifibrotic (prostacyclin [PGI(2)]) prostaglandins (PGs) when compared with normal human lung fibroblasts (HF-NL). METHODS: We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation. RESULTS: In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1β. PGE(2) was the predominant COX product in IL-1β-stimulated cells with no significant difference between HF-IPF and HF-NL (28.35 [9.09–89.09] vs. 17.12 [8.58–29.33] ng/10(6) cells/30 min, respectively; P = 0.25). TXB(2) (the stable metabolite of TXA(2)) production was significantly higher in IL-1β-stimulated HF-IPF compared to HF-NL (1.92 [1.27–2.57] vs. 0.61 [0.21–1.64] ng/10(6) cells/30 min, respectively; P = 0.007) and the ratio of PGI(2) (as measured by its stable metabolite 6-keto-PGF(1α)) to TXB(2) was significantly lower at baseline in HF-IPF (0.08 [0.04–0.52] vs. 0.12 [0.11–0.89] in HF-NL; P = 0.028) and with IL-1β stimulation (0.24 [0.05–1.53] vs. 1.08 [0.51–3.79] in HF-NL; P = 0.09). CONCLUSION: An alteration in the balance of profibrotic and antifibrotic PGs in HF-IPF may play a role in the pathogeneses of IPF

Lung cancer in view of the data collected by the National Health Fund between the years 2006-2009

Cel pracy. Celem pracy jest oszacowanie liczby nowych pacjentów z rozpoznanym rakiem płuca (według NFZ) w latach 2006-2009 wraz z analizą trendów czasowych, a następnie porównanie uzyskanych wyników z informacjami Krajowego Rejestru Nowotworów (KRN). Kolejnym celem jest zbadanie zależności pomiędzy standaryzowaną liczbą nowych pacjentów (według NFZ), a wielkością sprzedaży wyrobów tytoniowych (per capita). Materiał i metoda. Analizie poddano dane dotyczące leczenia nowotworu złośliwego płuca (C33-C34), przesłane do NFZ w latach 2004-2009, dla wszystkich rodzajów świadczeń. Wyniki. Średnia liczba nowych pacjentów z rozpoznanym rakiem płuca (C33-C34), według danych Narodowego Funduszu Zdrowia (NFZ) z lat 2006-2009, wyniosła w Polsce 11 196 dla kobiet i 23 629 dla mężczyzn. Leczenie szpitalne obejmowało około 70% chorych, z czego jedynie 40% obejmowała chemioterapia. Porównanie danych z NFZ z danymi Krajowego Rejestru Nowotworów (KRN) wykazało, że według NFZ liczba nowych przypadków nowotworu złośliwego płuca jest większa niż wskazują na to dane KRN. Analiza geograficzna wykazała, że najbardziej narażone na zachorowanie na ten nowotwór złośliwy są populacje z północnych województw Polski. Badanie zależności pomiędzy standaryzowaną liczbą nowych przypadków raka płuca według danych NFZ, a średnim poziomem wydatków na wyroby tytoniowe w przeliczeniu na 1 osobę wykazało obecność statystycznie istotnej korelacji pomiędzy tymi wartościami – współczynnik korelacji Pearsona = 0,48 (p=6,47*10-5). Wnioski. Przy rosnącej liczbie leczonych pacjentów liczba nowych świadczeniobiorców w latach 2006-2009 utrzymywała się na stałym poziomie, co może świadczyć o wzroście dostępności do leczenia onkologicznego w tym okresie. Niemożliwe okazało się ustalenie, czy brak zgodności pomiędzy danymi NFZ, a KRN wynika z niewielkiej sprawozdawczości do KRN z innych niż leczenie szpitalne rodzajów świadczeń, czy też jest odzwierciedleniem większej sprawozdawczości do NFZ, obejmującej nie tylko przypadki potwierdzone, ale także czynności medyczne podejmowane w kierunku potwierdzenia raka płuca. Badanie zależności pomiędzy standaryzowaną liczbą nowych pacjentów (według NFZ) a wielkością sprzedaży wyrobów tytoniowych (per capita) potwierdziło dodatnią korelację pomiędzy tymi zmiennymi.Aim of the thesis. The aim of the paper is to estimate the number of patients with newly diagnosed lung cancer (according to the National Health Fund) in the years 2006-2009, to analyse time-related trends, and to compare the obtained results with the information stored at the National Cancer Registry (NCR). We also examined the relationship between the standardised number of new patients (according to the National Health Fund) and the sales volume of tobacco products (per capita). Materials and method. WE analysed data concerning malignant lung cancer (C33-C34) sent to the National Health Fund in the years 2004-2009 for all kinds of services. Results. The average number of new patients with diagnosed lung cancer (C33-C34), according to the data collected by the National Health Fund in the years 2006-2009 in Poland, was 11,196 for women and 23,629 for men. Hospital treatment accounted for approx. 70% of the cases – among these patients only 40% received chemotherapy. A comparison of the National Health Fund data with the data collected by the National Cancer Registry showed that, according to the National Health Fund, the number of new cases of malignant lung carcinoma is larger. A geographic analysis revealed that populations from Poland’s northern provinces are at the greatest risk of developing this malignancy. An examination of the relationship between the standardised number of new cases of lung cancer, according to the National Health Fund data, and the average level of spending on tobacco products calculated per 1 person showed, that there exists a statistically significant correlation between these values – Pearson’s correlation coefficient of 0.48 (p=6.47*10-05). Conclusions. With the growing number of patients undergoing treatment, the number of new patients remained at the same level in the years 2006-2009, which may indicate greater accessibility of oncologic treatment in this period. It was impossible to determine whether the lack of correspondence between the National Health Fund and the National Cancer Registry results from insufficient reporting to the NCR concerning services other than hospital treatment or whether it reflects greater reporting to the National Health Fund, which includes not only confirmed cases, but also medical activities undertaken to confirm lung cancer. The examination of dependence between the standardised number of new patients (according to the National Health Fund) and the sales volumes of tobacco products (per capita) confirmed the existence of a positive correlation between these variables

Elucidating the Power in Empowerment and the Participation in Participatory Action Research: A Story About Research Team and Elementary School Change

Community psychologists are increasingly using Participatory Action Research (PAR) as a way to promote social justice by creating conditions that foster empowerment. Yet, little attention has been paid to the differences between the power structure that PAR advocates and the local community power structures. This paper seeks to evaluate the level of participation in a PAR project for multiple stakeholder groups, determine how PAR was adjusted to better fit community norms, and whether our research team was able to facilitate the emergence of PAR by adopting an approach that was relevant to the existing power relations. We conclude that power differences should not be seen as roadblocks to participation, but rather as moments of opportunity for the researchers to refine their methods and for the community and the community psychologist to challenge existing power structures

Neutrophil extracellular traps enhance early inflammatory response in Sendai virus-induced asthma phenotype

Paramyxoviral infection in childhood has been linked to a significant increased rate of asthma development. In mice, paramyxoviral infection with the mouse parainfluenza virus type I, Sendai virus (Sev), causes a limited bronchiolitis followed by persistent asthma traits. We have previously shown that the absence of cysteine protease dipeptidyl peptidase I (DPPI) dampened the acute lung inflammatory response and the subsequent asthma phenotype induced by Sev. Adoptive transfer of wild type neutrophils into DPPI-deficient mice restored leukocyte influx, the acute cytokine response, and the subsequent mucous cell metaplasia that accompanied Sev-induced asthma phenotype. However, the exact mechanism by which DPPI-sufficient neutrophils promote asthma development following Sev infection is still unknown. We hypothesize that neutrophils recruited to the alveolar space following Sev infection elaborate neutrophil extracellular traps (NETs) that propagate the inflammatory cascade, culminating in the eventual asthma phenotype. Indeed, we found that Sev infection was associated with NET formation in the lung and release of cell-free DNA complexed to myeloperoxidase (MPO) in the alveolar space and plasma that peaked on day 2-post infection. Absence of DPPI significantly attenuated Sev-induced NET formation in vivo and in vitro. Furthermore, concomitant administration of DNase 1, which dismantled NETs, or inhibition of peptidylarginine deiminase 4 (PAD4), an essential mediator of NET formation, suppressed the early inflammatory responses to Sev infection. Lastly, NETs primed bone marrow derived cells to release cytokines that can amplify the inflammatory cascade

Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (ΔIsc,amil), cAMP-dependent Cl- secretion (ΔIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (ΔIsc,ATP). In mice exposed to 98% PO2 for 36 hr, ΔIsc,forsk decreased, ΔIsc,amil and ΔIsc,ATP was not affected. In gulo(-/-) mice, both ΔIsc,forsk and ΔIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid

Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study

BACKGROUND: It has been suggested that cysteinyl leukotrienes (cysLTs) play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC). The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children. METHODS: 29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. RESULTS: EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range) 36.62 (22.60–101.05) versus 249.1 (74.21–526.36) pg/ml, p = 0.004). There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003). CONCLUSION: EBC cysLTs appear to be associated with RBM thickening in asthma

Low levels of tissue factor lead to alveolar hemorrhage, potentiating murine acute lung injury and oxidative stress

Systemic blockade of Tissue Factor (TF) attenuates acute lung injury (ALI) in animal models of sepsis but the effects of global TF deficiency are unknown