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8 záznamů v Medvik Filtry

Článek

Adipose tissue-derived mesenchymal stem cells attenuate lung inflammation and fibrosis in the bleomycin-induced pulmonary fibrosis rat model via caveolin-1/NF-kB signaling axis

Chen, Zhe
Autor Chen, Zhe Department of Respiratory and Critical Care Medicine, The First People's Hospital of Wenling, Zhejiang, China
Ruan, Bingqing
Autor Ruan, Bingqing Department of Internal Medicine, Wenling Women’s and Children’s Hospital, Zhejiang, China
Long, Guangyan
Autor Long, Guangyan Department of Infectious Diseases, The First People's Hospital of Wenling, Zhejiang, China
Lin, Wei
Autor Lin, Wei Department of Respirology, The First People's Hospital of Wenling, Zhejiang, China

Physiological research. 2022 ; 71 (5) : 657-666. [pub] 20220831

Physiol. Res. (Print)
ISSN 1802-9973
Medvik
Zdroj

Stem cells have emerged as promising therapeutic options for several human diseases, including pulmonary fibrosis (PF). In this study, we investigated the therapeutic effects of adipose tissue-derived mesenchymal stem cells (ADMSCs) in the bleomycin-induced PF model rats and the underlying mechanisms. The PF model rats were generated by intratracheal injections of 5 mg/kg bleomycin sulfate. The ADMSC group rats were generated by injecting 2×10(6) ADMSCs via the tail vein at 0, 12, and 24 h after bleomycin injection. The control, PF, and ADMSC group rats were sacrificed on day 21 after bleomycin injections and the changes in lung histology and the levels of pro-inflammatory cytokines, collagen I, and caveolin-1 (Cav-1), and the activity of the NF-kappaB signaling pathway in the lung tissues was assessed by hematoxylin-eosin staining, ELISA, and western blotting assays. The lung tissues of the PF model rats showed significant infiltration of neutrophils, tissue destruction, and collagen deposition, but these effects were abrogated by the ADMSCs. The levels of pro-inflammatory cytokines such as IL-6, IL-1beta, and TGF-beta1 were elevated in the lung tissues and the bronchoalveolar lavage fluid (BALF) of the bleomycin-induced PF model rats, but these effects were reversed by the ADMSCs. The lung tissues of the PF model rats showed significant downregulation of Cav-1 and significantly higher activation of the pro-inflammatory NF-kappaB pathway. However, administration of the ADMSCs restored the expression levels of Cav-1 and suppressed the NF-kappaB signaling pathway in the lungs of the bleomycin-induced PF model rats. In conclusion, this study demonstrated that the ADMSCs protected against bleomycin-induced PF in the rat model by modulating the Cav-1/NF-kappaB axis.

MeSH
bleomycin toxicita MeSH
cytokiny metabolismus MeSH
kaveolin 1 metabolismus farmakologie terapeutické užití MeSH
kolagen metabolismus MeSH
krysa rodu rattus MeSH
mezenchymální kmenové buňky * metabolismus MeSH
NF-kappa B metabolismus MeSH
plíce MeSH
plicní fibróza * chemicky indukované terapie metabolismus MeSH
pneumonie * metabolismus MeSH
potkani Sprague-Dawley MeSH
signální transdukce MeSH
zvířata MeSH
Check Tag
krysa rodu rattus MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH

Článek

Pleurální výpotky - cytologicko-energetická analýza versus tradiční Lightova kritéria
[Pleural effusion - cytological-energy analysis versus traditional Light's criteria]

Klinická biochemie a metabolismus. 2021 ; 29 (4) : 190-198.

ISSN 1210-7921
Medvik
Zdroj

Cíl studie: Porovnání diagnostické efektivity vyšetření pleurálních výpotků dle Lightových pravidel s jejich cytologicko-energetickou analýzou. Typ studie: Retrospektivní. Název a sídlo pracoviště: Biomedicínské centrum, Krajská zdravotní, a. s. - Masarykova nemocnice v Ústí nad Labem, o. z.; Ústav klinické imunologie a alergologie, LF UK v Hradci Králové a FN v Hradci Králové; Laboratoř pro likvorologii, neuroimunologii, patologii a speciální diagnostiku Topelex, s. r. o.; Oddělení hrudní chirurgie, Krajská zdravotní, a. s. - Masarykova nemocnice v Ústí nad Labem, o. z.; Oddělení klinické biochemie, Krajská zdravotní, a. s. - Masarykova nemocnice v Ústí nad Labem, o. z. Materiál a metody: Náš soubor pro tuto studii zahrnuje 96 případů nezánětlivých pleurálních výpotků od pacientů s kardiálním postižením či systémovou sepsí, 211 případů pleurálních výpotků od pacientů s purulentní pneumonií a 283 případů pleurálních výpotků od pacientů s hrudním empyémem. Ve všech případech jsme provedli vyšetření vybraných parametrů dle Lightových pravidel (počet jaderných elementů na 1 μl, koncentrace celkové bílkoviny, glukózy a laktátu a katalytická aktivita laktátdehydrogenázy (LDH)) a kompletní cytologicko-energetickou analýzu (četnost neutrofilních granulocytů, výpočet koeficientu energetické bilance (KEB) a katalytická aktivita aspartátaminotrasferázy (AST)). Pro statistické zhodnocení souboru jsme použili Kruskal-Wallisův test s vícenásobným porovnáním p-hodnot a ROC analýzu. Výsledky: Na úrovni všech zmíněných parametrů dle Lightových kritérií i cytologicko-energetické analýzy nacházíme při porovnání nezánětlivých a zánětlivých výpotků statisticky významné rozdíly (p < 0,01). Při porovnání výpotků pacientů s purulentními pneumoniemi a hrudními empyémy nacházíme statisticky významné diference (p < 0,01) v případě „Lightových“ počtů jaderných elementů, koncentrací celkové bílkoviny a laktátu a katalytických aktivit LDH a „cytologicko-energetických“ hodnot KEB a katalytických aktivit AST. Pro rozlišení nezánětlivých a parapneumonických výpotků dosáhly vysokou diagnostickou efektivitu „Lightovy“ koncentrace glukózy (AUC = 0,981), laktátu (AUC = 0,970) a katalytické aktivity LDH (AUC = 0,962) a „cytologicko- energetické“ četnosti neutrofilních granulocytů (AUC = 0,982), hodnoty KEB (AUC = 0,999) a katalytické aktivity AST (AUC = 0,954).Pro rozlišení nezánětlivých výpotků a výpotků pacientů s hrudními empyémy dosáhly vysokou diagnostickou efektivitu „Lightovy“ počty jaderných elementů (AUC = 0,939), koncentrace glukózy (AUC = 0,967), laktátu (AUC = 0,987) a katalytické aktivity LDH (AUC = 0,984) a „cytologicko-energetické“ četnosti neutrofilních granulocytů (AUC = 0,985), hodnoty KEB (AUC = 0,991) a katalytické aktivity AST (AUC = 0,979). Podstatně nižších diagnostických efektivit všech sledovaných parametrů bylo dosaženo při diferenciaci parapneumonických výpotků a výpotků pacientů s hrudními empyémy: „Lightovy“ počty jaderných elementů (AUC = 0,714), koncentrace glukózy (AUC = 0,631), laktátu (AUC = 0,721), celkové bílkoviny (AUC = 0,537) a katalytických aktivit LDH (AUC = 0,710) a „cytologicko-energetické“ četnosti neutrofilních granulocytů (AUC = 0,553), hodnot KEB (AUC = 0,671) a katalytických aktivit AST (AUC = 0,718). Závěr: Předností cytologicko-energetické analýzy oproti analýze pleurálních výpotků dle Lightových kritérií je charakteristika lokální imunitní odpovědi s ohledem na její energetické nároky. Obě metodiky se vhodně doplňují. V žádném případě si ale neodporují.

Objective: Comparison of diagnostic efficiency of Light's parameters with cytological-energy analysis parameters of pleural effusion. Design: retrospective. Settings: Biomedical Centre, Krajská zdravotní, a. s. - Masaryk Hospital in Ústí nad Labem, o. z.; Department of Clinical Immunology and Allergology, Faculty of Medicine and University Hospital in Hradec Králové, Charles University in Prague; Laboratory for Cerebrospinal Fluid, Neuroimmunology, Pathology and Special Diagnostics Topelex, s.r.o; Department of Thoracic Surgery, Krajská zdravotní, a.s. - Masaryk Hospital in Usti nad Labem, o.z.; Department of Clinical Biochemistry, Krajská zdravotní, a.s. – Masaryk Hospital in Ústí nad Labem, o.z. Material and Methods: The 96 samples of noninflammatory pleural effusions of patients with cardiac failure or systemic sepsis, the 211 samples of pleural effusions of patients with purulent pneumonia and the 283 samples of pleural effusions of patients with chest empyema were analysed. In all cases, we analysed selected parameters of Light criteria (total number of nuclear elements in 1 μl, concentration of total protein, glucose, lactate and catalytic activity of lactate dehydrogenase (LDH)) and parameters of cytological-energy analysis (frequency of neutrophils, KEB value and catalytic activity of aspartate aminotransferase (AST)). Statistical analysis was performed using the ANOVA Kruskal-Wallis test and ROC-analysis. Results: We found significant differences of parameters of Light‘s criteria and cytological-energy analysis between inflammatory and noninflammatory pleural effusions (p < 0.01). We found significant differences between patients with purulent pneumonia and chest empyema (p < 0.01). Light's criteria parameters included total number of nuclear elements, concentration of total protein, lactate and catalytic activities of LDH. Cytological-energy parameters included KEB value and catalytic activities of AST. We found high diagnostic accuracy of ,,Light's‘‘ concentration of glucose (AUC = 0.981), lactate (AUC = 0.970) and catalytic activities of LDH (AUC = 0.962) and ,,cytological-energy‘‘ frequency of neutrophils (AUC = 0.982), KEB values (AUC = 0.999) and catalytic activities of AST (AUC = 0.954) to distinguish between noninflammatory and parapneumonic pleural effusions. We found high diagnostic accuracy of „Light's“ total number of nuclear elements (AUC = 0.939), concentration of glucose (AUC = 0.967), lactate (AUC = 0.987) and catalytic activities of LDH (AUC = 0.984) and ,,cytological-energy‘‘ frequency of neutrophils (AUC = 0.985), KEB values (AUC = 0.991) and catalytic activities of AST (AUC = 0.979) to distinguish between noninflammatory pleural effusions and pleural effusions of patients with chest empyema. We found low diagnostic accuracy of all parameters to distinguish parapneumonic effusion and pleural effusion of patients with chest empyema: „Light's“ total number nuclear elements (AUC = 0.714), concentration of glucose (AUC = 0.631), lactate (AUC = 0.721), total protein (AUC = 0.537) and catalytic activities of LDH (AUC = 0.710) and „cytological-energy‘‘ frequency of neutrophils (AUC = 0.553), KEB values (AUC = 0.671) and catalytic activities of AST (AUC = 0.718). Conclusion: The advantage of cytological-energy analysis versus Light's criteria parameters is in their abilities to characterize a local immune response considering the energy state. Both methods complement each other appropriately. In any case, they do not contradict each other.

Klíčová slova
Lightova kritéria,
MeSH
empyém pleurální diagnóza metabolismus MeSH
lidé MeSH
pleurální výpotek * diagnóza metabolismus MeSH
pneumonie diagnóza metabolismus MeSH
retrospektivní studie MeSH
Check Tag
lidé MeSH

Článek

Cytological-energy analysis of pleural effusions with predominance of neutrophils

Therapeutic advances in respiratory disease. 2020 ; 14 (-) : 1753466620935772. [pub] -

Ther Adv Respir Dis
ISSN 1753-4666
Medvik
Zdroj

BACKGROUND: The predominance of neutrophils in pleural effusions of patients with different serious impairments of the pleural cavity organs is often found. The aim of this study was to identify the type of injury using the cytological-energy analysis of pleural effusions. METHODS: We analysed 635 samples of pleural effusions with predominance of neutrophils. We compared the values of the coefficient of energy balance (KEB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) catalytic activities in the following subgroups of patients: with transudative effusions, purulent pneumonia, chest empyema and after chest surgery with and without purulent complications. Statistical analysis was performed using the ANOVA Kruskal-Wallis test (p < 0.05 was considered as significant). RESULTS: We found the lowest KEB values in pleural effusions of patients with chest empyema and their gradual increases in patients with purulent pneumonia and with transudative effusions. We observed the highest LDH and AST enzymes activity in patients with chest empyema and their gradual decrease in patients with purulent pneumonia and with transudative effusions. LDH and AST enzymes activity was significantly higher in pleural effusions of patients after chest surgery with purulent complications compared with non-purulent cases. CONCLUSION: The most intensive inflammation and the most extensive tissue destruction in the pleural cavity were found in patients with chest empyema. Significantly better parameters were observed in patients with purulent pneumonia. The absence of serious inflammation and the absence of tissue destruction were typical for patients with transudative effusions. Finally, our results confirmed an anticipated higher tissue destruction in patients after chest surgery. Significantly worse injury was found in surgical patients with purulent complications compared with non-purulent ones. The reviews of this paper are available via the supplemental material section.

MeSH
aspartátaminotransferasy analýza MeSH
biologické markery analýza MeSH
empyém pleurální diagnóza imunologie metabolismus MeSH
energetický metabolismus * MeSH
hrudní chirurgické výkony škodlivé účinky MeSH
L-laktátdehydrogenasa analýza MeSH
lidé MeSH
neutrofily imunologie metabolismus MeSH
pleurální výpotek diagnóza imunologie metabolismus MeSH
pneumonie diagnóza imunologie metabolismus MeSH
pooperační komplikace diagnóza imunologie metabolismus MeSH
retrospektivní studie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Reduction of lung inflammation, oxidative stress and apoptosis by the PDE4 inhibitor roflumilast in experimental model of acute lung injury

Physiological research. 2018 ; 67 (Suppl. 4) : S645-S654.

Physiol. Res. (Print)
ISSN 1802-9973
Medvik
Zdroj

Proceedings of the ... Physiological days. 2018 ; 94 (Suppl. 4) : S645-S654.

ISSN 1802-9973
Medvik
Zdroj

Damage of alveolar-capillary barrier, inflammation, oxidative injury, and lung cell apoptosis represent the key features of acute lung injury (ALI). This study evaluated if selective phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the mentioned changes in lavage-induced model of ALI. Rabbits with ALI were divided into 2 groups: ALI without therapy (A group) and ALI treated with roflumilast i.v. (1 mg/kg; A+R group). One group of healthy animals without ALI served as ventilated controls (C group). All animals were oxygen-ventilated for further 4 h. At the end of experiment, total and differential counts of cells in bronchoalveolar lavage fluid (BALF) and total and differential counts of white blood cells were estimated. Lung edema formation was assessed from determination of protein content in BALF. Pro-inflammatory cytokines (TNFalpha, IL-6 and IL-8) and markers of oxidation (3-nitrotyrosine, thiobarbituric-acid reactive substances) were detected in the lung tissue and plasma. Apoptosis of lung cells was investigated immunohistochemically. Treatment with roflumilast reduced leak of cells, particularly of neutrophils, into the lung, decreased concentrations of cytokines and oxidative products in the lung and plasma, and reduced lung cell apoptosis and edema formation. Concluding, PDE4 inhibitor roflumilast showed potent anti-inflammatory actions in this model of ALI.

Článek

Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis

Chest. 2016 ; 150 (3) : 661-72. [pub] 20160419

ISSN 1931-3543
Medvik
Zdroj

BACKGROUND: Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. METHODS: Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. RESULTS: Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. CONCLUSIONS: HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

Článek

Redox-sensitive regulation of macrophage-inducible nitric oxide synthase expression in vitro does not correlate with the failure of apocynin to prevent lung inflammation induced by endotoxin

Immunobiology. 2011 ; 216 (4) : 457-65.

ISSN 1878-3279
Medvik
Zdroj

Reactive oxygen and nitrogen species are among the crucial mediators in the development of the pathological inflammatory process in the lungs and contribute to the damage of lung epithelium. The aim of the present study was to evaluate the potential of selected antioxidants or inhibitors of NADPH oxidase (glutathione, N-acetyl cysteine, trolox, apocynin, and diphenyleneiodonium chloride) to modulate nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by mouse macrophages induced by lipopolysaccharide (LPS) in vitro and to evaluate the potential of apocynin to modulate the course of LPS-induced lung inflammation in vivo. All the tested drugs revealed inhibitory effects on LPS-induced NO production and iNOS expression in RAW 264.7 macrophages. Further, apocynin significantly inhibited activation of nuclear factor kappa B induced by LPS. Ex vivo, diphenyleneiodonium chloride and apocynin significantly reduced ROS production by inflammatory cells isolated from bronchoalveolar lavage fluid. In contrast, in vivo intranasal application of apocynin did not exert any significant effect on the course of lung inflammation in mice induced by LPS that was evaluated based on the accumulation of cells, interleukine-6, interleukine-12, RANTES, tumor necrosis factor-alpha, and protein concentration in bronchoalveolar lavage fluid and expression of iNOS in lung tissue. Only effected were the levels of nitrites 36 h after induction of lung inflammation that were reduced in the apocynin-treated group. In conclusion, our data suggest that the inhibitors of NADPH oxidase possess inhibitory potential against LPS-induced NO production by mouse macrophages; however, apocynin failed to reduce LPS-induced lung inflammation in mice.