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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

At least 163 records · Page 9Linked to original sources
PubMed1995

Changes of intracellular free calcium concentration in human polymorphonuclear leukocytes after repeated stimulations with N-formyl-methionyl-leucyl-phenylalanine.

A rapid transient rise in the intracellular free calcium concentration ( Ca2+]i) is an important step in human polymorphonuclear leukocytes (PMNL) activation. This can be caused by many inflammatory mediators and has been implicated in the regulation of various cellular reactions. In this study we investigated the changes of [Ca2+]i in human PMNL activated three times with 10(-7)M n-formyl-methionyl-leucyl-phenylalanine (FMLP). PMNL in the presence of 1 mM Ca2+ were able to respond to three consecutive stimulations with FMLP. The first Ca2+ response was the highest one and was a result of Ca2+ release from internal stores (which was responsible for about 30% of maximal increment in [Ca2+]i) and the extracellular Ca2+ influx. Experiments with PMNL suspended in a medium containing 100 nM Ca2+ and pretreated with 1 nM Ni2+ (an inorganic calcium channel blocker) revealed that the second and third response is completely dependent on the extracellular Ca2+ influx. Changes of the time interval between stimulations had no influence on the occurrence of extracellular Ca2+ influx related to second addition of FMLP. Elongation of the time interval up to 30 min did not restore the release of Ca2+ from internal stores. It indicates the occurrence of dissociation of Ca2+ release from intracellular stores and extracellular Ca2+ influx during the second and third PMNL response to FMLP.

Calcium↗
PubMed1995

The effect of 1 ppm nitrogen dioxide on bronchoalveolar lavage cells and inflammatory mediators in normal and asthmatic subjects.

Several studies have suggested that patients with bronchial asthma are more susceptible to the potential effects of nitrogen dioxide (NO2) than healthy subjects, with respect to airway responsiveness and lung function. We investigated whether these differences are paralleled by differences in the cellular and biochemical response within the airway lumen. Twelve subjects with mild extrinsic asthma and eight normal subjects breathed either filtered air or 1 ppm NO2 in a single-blind manner during intermittent exercise for 3 h. Bronchoscopy with bronchoalveolar lavage (BAL) was performed one hour after each exposure, and on a third day without exposure (baseline day). Prostanoids, leukotrienes and histamine were analysed in BAL fluid, and the cellular composition of BAL fluid was assessed. In the asthmatic subjects, NO2 induced a small mean drop in forced expiratory volume in one second (FEV1). Differential cell counts in BAL fluid did not reveal significant effects of NO2. Levels of 6-keto-prostaglandin1 alpha (6-keto-PGF1 alpha) were decreased, and levels of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2) in BAL fluid were increased after NO2 compared to filtered air exposure; whereas, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), histamine and leukotriene levels did not change significantly. The normal subjects showed no change in lung function parameters and a small increase in TxB2 after breathing NO2. We conclude that in subjects with mild asthma NO2 is capable of inducing an activation of cells, which is compatible with enhancement of airway inflammation, even if lung function parameters and cellular composition of BAL fluid are not markedly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Modulation of fibroblast activity in histiocytosis X by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibrosis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidence of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B-chain of PDGF) expression was measured by gene hybridization revealing an upregulated c-sis transcript in the group of histiocytosis X and patients, whereas no c-sis expression was detectable in the control group. The alveolar macrophage supernatants from histiocytosis X patients and from the control group were incubated with a human lung fibroblast cell line (WI-38). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen III peptide concentration in fibroblast supernatants. Tritiated thymidine uptake was increased 1.6 times in histiocytosis X compared with the control group (p < 0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants from histiocytosis X were elevated 2.5 times compared with the control group (p < 0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (AA- and BB-chain) resulting in an 80% decrease of tritiated thymidine uptake and procollagen-III-peptide production in the group of histiocytosis X patients compared with native supernatants. No significant change in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T-lymphocyte marker did not show significant differences in both groups excluding unspecific antibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen production.

Adult↗
PubMed1995

[Effect of tobacco smoke on serum antioxidant activity].

Oxidants of cigarette smoke and those released from phagocytes in smoker's lungs may inactivate alpha-1-antiproteinase. Thus, the "elastase-antielastase" imbalance may lead to lung tissue destruction and emphysema. Insufficient antioxidant protection, postulated by some authors might be an additional factor contributing to this process. The presented data on the influence of acute in vitro exposure to cigarette smoke in humans did not show difference in serum antioxidant activity (AOA) before and after the exposure. Attempts were made to evaluate the effect of whole cigarette smoke, its gas-phase and water-soluble phase on serum AOA in vitro. The results show that gas-phase leads to the depletion of serum AOA, whereas water-soluble phase exerts protective effect. Thus, at least part of oxidants might be inactivated in the stream of inhaled smoke. In conclusion, we doubt that serum AOA is influenced as a result of smoking and that the depletion of serum AOA is a decisive factor in the development of pulmonary emphysema.

Adult↗
PubMed1995

[Evaluation of selected factors induced by antioxidative activity in serum of cigarette smokers and in patients with early phase emphysema].

We investigated the concentration of ceruloplasmin (CP), transferrin (T) and metal ions (Cu, Zn) in serum of healthy smokers, emphysema patients and healty non-smoking subjects (control). We observed elevated Cu concentration in smokers and emphysema patients. Elevated CP concentration was observed only in those emphysema patients who smoked cigarettes, but not in healthy smokers. This observation excludes the possibility of compensative CP and Cu increase as the effect of chronic oxidant exposure. Changes in concentration of CP and Cu observed by us are probably due to chronic inflammation of respiratory tract not only of emphysema patients but also of chronic smokers without signs of the disease.

Adult↗
PubMed1995

Influence of gold salts treatment on the serum concentration of IL-1 and IL-2 in patients with rheumatoid arthritis.

Eighteen subjects (2 males, 16 females) with rheumatoid arthritis were treated with gold salts for 6 months. The statistically significant decrease of IL-1 and IL-2 levels during the treatment was observed. The mean serum concentrations of IL-1 and IL-2 decreased from 41.0 +/- 11.5 to 28.6 +/- 7.3 (p < 0.001) and 98.3 +/- 57.6 to 29.3 +/- 20.5 fmol/ml (p < 0.001), respectively. This decrease was accompanied by a decline of serum concentration of acute phase proteins and immunoglobulins. These results can explain a strong anti-inflammatory action of gold salts in patients with rheumatoid arthritis.

Adult↗
PubMed1994

DNase-I-like enzyme from the carp liver--inhibition by muscle and endogenous actin.

1. DNase-I-like activity occurs in the carp (Cyprinus carpio) liver cytosol (supernatant 105,000 g). 2. The enzyme resembles DNase I from bovine pancreas in respect to the molecular mass (approximately 31 kDa), pH (7.4) and ion requirements (Mg2+, Ca2+) and the ability to degrade native as well as denatured DNA. 3. As judged by comparison of DNase zymograms obtained after native- and SDS-PAGE, the enzyme occurs in the three molecular forms of similar molecular weight and different charges. 4. All these forms are inhibited by rabbit skeletal muscle actin as well as by endogenous actin isolated from the carp liver cytosol. 5. DNase from the carp liver cytosol does not interact with the antibodies directed against DNase I from bovine pancreas and against DNase I from the rat and bovine parotid glands.

Actins↗
PubMed1994

Antioxidant properties of Ambroxol.

We tested whether Ambroxol, a drug which stimulates the release of surfactant by pneumocytes type II, may also possess antioxidant properties. To assess the reactivity of Ambroxol with reactive oxygen species, we analysed its ability to decompose hydrogen peroxide (H2O2) and to inhibit the superoxide (O2.-)-dependent autooxidation of pyrogallol, hydroxyl radical (.OH)-mediated deoxyribose oxidation, and hypochlorous acid (HClO-induced chlorination of monochlorodimedon. Ambroxol was found to be a sufficient scavenger of HClO and .OH and also revealed the capacity to decompose H2O2. At concentrations of 25 and 70 microM, it inhibited HClO-induced chlorination of monochlorodimedon by 22 +/- 13 and 59 +/- 14%, respectively. Similarly, at concentrations of 1, 2, and 10 mM, Ambroxol decreased .OH-mediated deoxyribose oxidation by 47 +/- 11, 75 +/- 9, and 89 +/- 4%. In addition, at concentrations of 1 to 5 mM, it completely protected linoleic acid from .OH-induced peroxidative damage. Ambroxol had a weak effect on O2.(-)-dependent autooxidation of pyrogallol. Our results indicate that Ambroxol has antioxidant activity, which may have clinical significance in protecting lung tissue from oxidant-induced injury.

Ambroxol↗
PubMed1994

Protective effect of ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice.

We wanted to determine whether ambroxol, a drug which stimulates the release of surfactant by type II pneumocytes, can protect lung lipids from peroxidative damage in mice. Animals were injected intraperitoneally with ambroxol, 0.169 mmol.kg-1, or 1 ml buffer once a day for three consecutive days. Lipid peroxidation was then induced in lung homogenates either by means of heat, 50 degrees C, or H2O2, 10 mmol.l-1. The lung homogenates from ambroxol-treated animals revealed decreased lipid peroxidation in response to both stimuli. The heat- and H2O2-induced generation of conjugated dienes (a first lipid peroxidation product) in ambroxol-treated lung homogenates was 3.7 and 3.1 fold lower than in the lungs from buffer-injected mice. Ambroxol, as an inhibitor of heat- and H2O2-induced lipid peroxidation, was equipotent to and stronger than the two antioxidants, N-acetylcysteine and methionine, respectively. Ambroxol was not able to protect heart and liver lipids. These results suggest that ambroxol can sufficiently enhance the antioxidant defence in lung tissue and can act as a lung lipid antioxidant.

Acetylcysteine↗
PubMed1994

[Experimental effects of air pollutants on healthy probands and asthmatic patients].

We investigated the acute airway response to nitrogen dioxide (NO2) and ozone in healthy and asthmatic subjects. A) 12 subjects with mild bronchial asthma and 8 healthy subjects were studied to determine the effects of shortterm exposure to NO2 on lung function, bronchoalveolar lavage cells and mediators, and bronchial mucosal biopsy specimens. The asthmatic subjects exhibited changes in prostanoid and leukotriene mediators but no changes in differential cell numbers after NO2 exposure, whereas the normal subjects showed no consistent effects. These results indicate that changes in mediator profile induced by NO2 may be found without concomitant alterations in differential cell numbers. B) Ozone has been demonstrated to induce deterioration of lung function and bronchial responsiveness but it is not clear whether subjects with asthma or rhinitis are more susceptible than normals. We studied the effect of a short-term exposure to ozone on lung function and airway responsiveness to methacholine in 12 subjects with atopic asthma, 18 subjects with allergic rhinitis, and 38 healthy subjects. There was a large interindividual variability in the airway response to ozone but no statistically significant difference between study groups with respect to changes of lung function and airway responsiveness. Our data indicate that an intrinsic variability in ozone sensitivity is of higher relevance than a pre-existing airway disease such as asthma or rhinitis. By comparing both studies we suggest that the relationship between airway disease and airway responsiveness to oxidant pollutants is not homogeneous over substances.

Adult↗
PubMed1993

[Diagnosis of bronchopulmonary aspergillosis is often made too late].

ABPA may occur in patients with longstanding bronchial asthma. The most important diagnostic criteria include a history of asthma with peripheral blood eosinophilia, immediate skin reactivity, elevated serum IgE, precipitating antibodies against Aspergillus species, migrating infiltrates, and central bronchiectases. Here we report on the clinical characteristics in 15 patients in whom the diagnosis of ABPA could be established. Mean diagnostic latency between the occurrence of first symptoms and the diagnosis was 10 +/- 10 years. We therefore conclude that the diagnosis and therapy of ABPA is often delayed.

Adult↗
PubMed1993

Effect of bacterial lipopolysaccharide on the content of lipid peroxidation products in lungs and other organs of mice.

The influence of lipopolysaccharide from Escherichia coli (LPS, 17 mg/kg body weight) on the lipid peroxidation process in organs of mice was studied. The content of conjugated dienes (CD), lipid peroxides (LP), malondialdehyde (MDA) (all three lipid peroxidation by-products), peroxidase (PO) activity and wet-to-dry weight ratio in lungs, heart, spleen, kidneys and liver were determined 1.5 h after intravenous injection of LPS. Animals observed at this time-point had reduced activity and decreased body temperature by about 2 degrees C, however, all analysed organs did not reveal any changes of wet-to-dry weight ratio comparing to organs from mice injected with sterile, pyrogen free 0.9% NaCl. Only extracts from heart and lungs showed significant increase in the tissue level of at least two lipid peroxidation products. The heart content of CD, MDA, and LP was about 1.5-, 1.3-, and 2.4-fold higher than in control group. In lungs CD and MDA increased 3.3- and 1.3-times but in spleen only content of LP was elevated. In these organs the suppression of PO activity was also observed. Liver and kidneys did not reveal any convincing enhancement of lipid peroxidation process and alterations of PO activity. Since free radical reactions are involved in lipid peroxidation process and inactivation of PO these results suggest that heart, lungs and spleen are the organs mostly exposed to oxidative stress during the first 1.5 h after single injection of LPS in mice.

Animals↗