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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

At least 19 recordsLinked to original sources
PubMed1996

The effect of ozone exposure on allergen responsiveness in subjects with asthma or rhinitis.

The aim of this study was to determine whether ozone enhances bronchial responsiveness to allergens in subjects with allergic asthma, or facilitates a bronchial response in subjects with allergic rhinitis. Twenty-four subjects with mild stable allergic asthma, 12 subjects with allergic rhinitis without asthma, and 10 healthy subjects participated in the study. Subjects breathed 250 ppb ozone or filtered air (FA) for 3 h of intermittent exercise. Airway responsiveness to methacholine was determined 1 h before and after exposures, and allergen responsiveness 3 h after exposures. We determined the concentration of methacholine (PC20FEV1) and the dose of allergen (PD20FEV1) producing a 20% fall in FEV1. In the subjects with asthma, FEV1 decreased by 12.5 +/- 2.2% (mean +/- SEM; p = 0.0001), PC20FEV1 of methacholine by 0.91 +/- 0.19 doubling concentrations (p = 0.0001) and PD20FEV1 of allergen by 1.74 +/- 0.25 doubling doses (p < 0.0001) after ozone compared with FA. The changes in lung function, methacholine, and allergen responsiveness did not correlate with each other. In the subjects with rhinitis, mean FEV1 decreased by 7.8% and 1.3% when ozone or FA, respectively, were followed by allergen inhalation (p = 0.035). Therefore, our data suggest that short-term exposure to ozone can increase bronchial allergen responsiveness in subjects with mild allergic asthma or rhinitis.

Adult↗
PubMed1996

Increased content of hydrogen peroxide in the expired breath of cigarette smokers.

Cigarette smoking causes an influx of mononuclear phagocytes and polymorphonuclear leucocytes into the lower airways. These cells have altered oxygen metabolism and release more H2O2 than phagocytes from nonsmokers. In this study, we intended to determine whether asymptomatic cigarette smokers exhale more H2O2 than healthy nonsmokers. The content of H2O2 in the expired condensate of 27 nonsmokers and 33 cigarette smokers was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 level in the expired breath condensate of all cigarette smokers was about fivefold higher than that found in the whole nonsmoker group (0.24 +/- 0.32 versus 0.05 +/- 0.11 nM). However, only 16 smokers (49%) and 6 nonsmokers (22%) had detectable levels of H2O2 in expired breath that reached values 0.49 +/- 0.28 and 0.23 +/- 0.10 nM, respectively. Although the cigarette smoking status was similar for both male and female smokers, females expired 2.5 fold less H2O2 than males (0.15 +/- 0.24 (n = 21) versus 0.38 +/- 0.39 (n = 12) nM. No correlation was found between expired H2O2 levels and cigarette smoking status expressed as the daily cigarette consumption, cumulative cigarette consumption and urinary cotinine concentration. It is suggested that in some smokers, expressed H2O2 can be a noninvasive marker of oxidant overload in the lower airways related to cigarette smoking.

Adult↗
PubMed1996

[Bronchial asthma--a cost of illness analysis].

We performed an economic evaluation of the costs of asthma in Germany. Estimates of direct medical expenditures and indirect costs were derived from official health statistics of 1992. Adding up direct and indirect costs, the total sum is approximately 2.66 billions ECU which is equivalent to 5.13 billions DM or 3.11 billions US-$, respectively, for a total population of 80.3 millions. Direct costs make up 61.5% of this sum and comprise of outpatient medical care, drugs, hospital treatment, rehabilitation and compensation for occupational asthma as well as sickness benefits. Indirect costs of 38.5% are caused by payments for days off work, premature retirement and premature death due to asthma. Based on these figures, we speculate that an optimised treatment according to published recommendations should be accompanied by a reduction of the high amount of indirect costs.

Asthma↗
PubMed1995

Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes.

In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized. The BAL fluid of nine patients with histologically proven isolated pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.

Adult↗
PubMed1995

Short term effect of methotrexate in severe steroid-dependent asthma.

The steroid-sparing capacity of methotrexate in asthmatics is still being debated. The present study was undertaken to evaluate the effect of low-dose methotrexate on steroid consumption in patients with severe asthma, who require very high doses of systemic corticosteroids. We conducted a randomized, double-blind, parallel clinical trial in 24 patients with long-standing asthma. After a 3-week run-in period, patients received a 16-week course of either 15 mg of oral methotrexate weekly or matched placebo in addition to their previous asthma therapy. The daily steroid dose (at run-in 30 +/- 14 mg/day in the methotrexate group; 25 +/- 9 mg/day in the placebo group (NS)) decreased by 24% in the methotrexate group (p < 0.01) and by 5% in the placebo group (NS) during weeks 9-16 of the treatment period when compared with run-in values. However, there was no difference in steroid consumption between the two groups at any time. We conclude that in patients with severe asthma who require very high doses of systemic corticosteroids, short-term treatment with methotrexate allows only a marginal steroid reduction. Our study does not support the use of methotrexate as a steroid-sparing agent in asthmatics.

Administration, Oral↗
PubMed1995

Effect of cytochalasin B on intracellular free calcium concentration in human polymorphonuclear leukocytes after repeated stimulation with n-formyl-methionyl-leucyl-phenylalanine.

Cytochalasin B can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, lysosomal enzyme release, and reactive oxygen species generation. In this study we investigated the effect of cytochalasin B on the increase in intracellular free calcium concentration after three consecutive additions of 10(-7) M N-formyl-methionyl-leucyl-phenylalanine. The interval between stimulations was 5 min. Intracellular free calcium concentration was monitored using the fluorescent calcium indicator FURA-2AM. Cytochalasin B (3.3 micrograms/ml) added 60 s before the cell stimulation enhanced all three polymorphonuclear leukocyte calcium responses by increasing the N-formyl-methionyl-leucyl-phenylalanine-induced calcium influx from the extracellular space. Cytochalasin B increased the peak intracellular free calcium concentration and elevated the plateau phase level, but had no influence on its shape. In addition, pretreatment with cytochalasin B of polymorphonuclear leukocytes suspended in low calcium medium restored their capacity to respond to a third stimulation with N-formyl-methionyl-leucyl-phenylalanine. Finally, in resting cells cytochalasin B caused a moderate increase in intracellular free calcium concentration which was independent of extracellular calcium.

Adult↗
PubMed1995

Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice.

A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weight) caused a significant rise in the content of lipid peroxidation products in hearts of mice. The concentration of conjugated dienes (CD) and malondialdehyde (MDA) found 24 h after injection of DOX increased about 1.8- and 2.4-fold and reached values of 11.31 +/- 2.24 A233/g and 3.72 +/- 0.40 mumol/g, respectively. The same dose of 4'-epi-doxorubicin (EPI), a less cardiotoxic epimer of DOX, increased only the heart level of MDA. Both antracyclines were not able to induce increased formation of CD in murine liver and lungs. Ambroxol, an expectorant drug which possesses the ability to scavenge hydroxyl radicals, injected intravenously (70 mg/kg) 30 min prior to DOX, completely abolished the rise in heart content of CD and MDA. The heart levels of CD and MDA in animals treated with ambroxol and DOX were 3 and 2.7 times lower than those observed in mice treated with water and DOX, respectively. Ambroxol had no effect on DOX- and EPI-induced formation of MDA in the lungs. Our results indicate that (1) DOX is a more powerful inductor lipid peroxidation in the heart than EPI; and (2) ambroxol may be useful in preventing lipid peroxidation in the heart caused by DOX.

Ambroxol↗
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↗