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D Nowak

Publications and source records attributed to D Nowak.

At least 19 recordsLinked to original sources
PubMed1998

Correlations between DNA and cytogenetic damage induced after chemical treatment and radiation.

The induction of damage in human lymphocytes has been compared after treatment in vitro with two different agents, the chemical o-phenylenediamine (o-PDA) and gamma irradiation, in the alkaline single cell gel electrophoresis (Comet) assay, and after cytogenetic analysis. The chemical treatment caused dose-related increases in DNA damage in the Comet assay and cytogenetic damage in the first and second metaphases. The results revealed a very strong association between the two types of damage. Correlation coefficients were from 0.95 to 0.97. From previous studies, high correlation coefficients of 0.99 and 0.97 in the same assays were also evaluated for X-rays and fast neutrons, respectively. On the basis of such results, we suggest that the Comet assay responses provide a good prediction of cytogenetic damage. Thus, because of its simplicity and rapidity, the Comet assay would appear to be a very useful tool for determining the genotoxicity of environmental agents.

Chromosome Aberrations↗
PubMed1998

Effect of various agonists on nitric oxide generation by human polymorphonuclear leukocytes.

Nitric oxide generation is involved in a range of diseases involving polymorphonuclear leukocytes. The aim of this study was to determine whether human polymorphonuclear leukocytes are able to generate nitric oxide and to investigate the time course of its generation after stimulation with 10(-7) M N-formyl-methionyl-leucyl-phenylalanine, 60 ng/ml phorbol myristate acetate, 10(-7) M concanavalin A, and 10(-7) M platelet activating factor. Stimulation of human polymorphonuclear leukocytes with N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate caused sustained nitric oxide generation, reaching maximal values of 1,105 +/- 361 nM (n = 32) and 628 +/- 119 nM (n = 30), respectively. Platelet activating factor did not affect nitric oxide production (maximal value 29 +/- 7 nM, n = 8), whereas concanavalin A caused only a slight increase (102 +/- 24 nM, n = 8) when compared with resting cells control (26 +/- 6 nM, n = 8). Human polymorphonuclear leukocytes were able to respond to both consecutive and alternate N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate stimulation with nitric oxide generation. Nitric oxide generation was inhibited by specific inhibitors (N omega-nitro-L-arginine and N omega-monomethyl-L-arginine) and restored with L-arginine. We provide, to our knowledge, the first direct evidence that human neutrophils generate nitric oxide.

Concanavalin A↗
PubMed1998

Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.

Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.

Administration, Inhalation↗
PubMed1998

Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.

Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have both been frequently investigated. Because of its SH group, NAC scavenges H2O2 (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid). Furthermore, NAC can easily be deacetylated to cysteine, an important precursor of cellular glutathione synthesis, and thus stimulate the cellular glutathione system. This is most evident in pulmonary diseases characterized by low glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication and may even be protective against side-effects of mutagenic agents. In addition NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL-1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces bronchial hyperreactivity, and it is known to stimulate cellular surfactant production. In addition, ambroxol has anti-inflammatory properties owing to its inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. For both substances effective anti-oxidant and anti-inflammatory function has been validated when used in micromolar concentrations. These levels are attainable in vivo in humans. This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol.

Acetylcysteine↗
PubMed1998

Age-dependent differences in the prevalence of allergic rhinitis and atopic sensitization between an eastern and a western German city.

Recent studies have found a higher prevalence of allergic rhinitis and atopic sensitization among adults living in eastern than those living in western Germany. We hypothesize that prevalence rates were similar before Germany was divided and diverged after the division. Because there are no historical data comparing atopic status between the two parts of Germany, we tested this hypothesis by comparing the prevalence of atopy among persons who were born during different decades. As part of the EC Respiratory Health Survey, a respiratory health questionnaire was mailed to a population-based sample of 8363 subjects aged 20-44 years from a city in the former West Germany (Hamburg) and a city in the former East Germany (Erfurt). Of the target population, 6428 (77%) subjects responded. Subsamples of 731 subjects from Erfurt and 1159 subjects from Hamburg participated in medical examinations, including skin prick tests and specific IgE measurements. Prevalence rates of allergic sensitization were similar in Hamburg and Erfurt for those born in the periods 1946-51 and 1952-61, respectively, but differed between Hamburg and Erfurt subjects born in the period 1962-71. After adjustment for several potential predictors, the younger subjects from Hamburg had a higher odds ratio (OR) of sensitization than those Hamburg subjects born before 1952 (skin prick test reactivity: OR 2.06, any specific IgE > 0.35 kU/l: OR 1.61). The younger subjects from Erfurt were not more frequently sensitized than the older subjects (skin prick test reactivity: OR 1.05, any specific IgE > 0.35 kU/l: OR 0.79). No single allergen could be identified as responsible for the observed difference. We conclude that factors related to a "Western lifestyle", which were prevalent in the West German city during the 1960s and 1970s, may be responsible for the higher prevalence of allergic sensitization observed in Hamburg.

Adult↗
PubMed1998

References values for forced spirometry. Group of the European Community Respiratory Health Survey.

The European Coal and Steel Community (ECSC) prediction equations exemplify a significant effort carried out approximately 15 yrs ago to provide uniform standards for lung function testing, but this set of equations has not been properly validated as yet. The present study evaluates the ECSC reference values and four other sets of prediction equations, using spirometric data collected in 12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers) aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS). Standardized spirometric measurements were obtained using a common protocol in 34 centres in 14 countries. For each prediction equation, the prediction deviations (i.e. observed minus predicted value) for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined for the whole study population and for each centre. For the age range included, the errors about the ECSC equations showed the most prominent underestimation of both predicted FVC (+355 and +360 mL on average in males and females, respectively) and predicted FEV1 (+211 and +200 mL, respectively) among the five studies examined. As expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower than in lifetime nonsmokers (each p<0.01). We conclude that the present European recommendations on lung function reference values should be reconsidered, but further data for nonsymptomatic subjects above the age of 44 yrs are needed.

Adult↗
PubMed1998

[Almitrine in therapy of chronic obstructive respiratory tract diseases with hypoxemia--a clinical multicenter study comparing 2 dosages].

In an 8-month prospective, placebo-controlled multi-centre trial involving 64 hypoxaemic COPD patients (mean +/- SD age, 64 +/- 8 years, paO2, 57 +/- 7 mmHg, paCO2, 41 +/- 6 mmHg), we compared the efficacy and acceptability of two different dosages of almitrine, 75 and 100 mg. 21 patients received continuous treatment with almitrine (75 mg), 23 sequential treatment (100 mg, one month of placebo after three months treatment), and 20 were in the placebo group. As defined by the inclusion criteria, none of the patients had clinical or subclinical signs of peripheral neuropathy. Clinical examinations, blood gas analyses and determinations of plasma almitrine levels were performed monthly. Patients underwent spirometry and detailed neurological examination upon entry and at the end of the trial. The percentage of drop-outs was considerably higher among patients under medication (59%) as compared to placebo (10%, p < 0.001) which was particularly due to impaired compliance in the almitrine groups. Comparing arterial paO2 or paCO2 over time by analysis of variance, there was no significant effect of medication on blood gases. However, in patients receiving 100 mg almitrine daily, paO2 was significantly increased vs. placebo after four and six months of treatment, and in patients receiving 75 mg almitrine, mean paCO2 was significantly lowered vs. placebo after four months of medication (t-test, p < 0.05). Neurological findings did not differ between treatments and over time. In conclusion, only certain individual patients may benefit from a treatment with 100 mg almitrine whereas the effect of the 75 mg dosage on paO2 did not differ from placebo.

Aged↗
PubMed1998

Effect of serine proteinase inhibitors on intracellular free calcium rise in human polymorphonuclear leukocytes after stimulation with receptor agonists.

The respiratory burst of polymorphonuclear leukocytes depends on activation of many enzymes and generation of variety of second messengers. One of important links leading to polymorphonuclear leukocytes (PMNL) activation is a transient rise in intracellular free calcium concentration ([Ca2+]i). Serine proteinase inhibitors such as alpha-1-proteinase inhibitor (alpha1PI), phenylmethylsulphonylfluoride (PMSF) and soybean trypsin inhibitor (SBTI) were reported to inhibit human PMNL respiratory burst. In this study we tested the hypothesis whether these inhibitors can inhibit the rise in [Ca2+]i after stimulation of human PMNL with 10(-7) M n-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) or platelet activating factor (PAF). [Ca2+]i was measured with use of a fluorescent probe Fura-2AM under conditions of 100 nM and 1 mM extracellular Ca2+ concentration. Preincubation of PML with 600 mg/dl of alpha1PI or SBTI for 30 min at 37 degrees C had no influence on Ca2+ response to all agonists in comparison with cells treated with the same concentration of human serum albumin. However, 0.5 mM PMSF enhanced 1.7-fold (p < 0.002) [Ca2+]i rise after challenge with FMLP while did not affect significantly Ca2+ response to PAF and LTB4. The stimulatory effect of PMSF after addition of FMLP was dependent on increased Ca2+ influx from extracellular space. Our results suggest that suppression of PMNL respiratory burst by serine proteinase inhibitors is not mediated via Ca2+ pathway and that some proteases take part in Ca2+ response to FMLP.

Adult↗
PubMed1998

[Health effects of airborne pollutants, particularly in swine confinement stalls, from the viewpoint of occupational medicine].

From the point of view of occupational respiratory medicine, an overview on potential health effects of airborne pollutants particularly in swine confinement houses is presented. Airway diseases are the most frequent occupational disorders among farmers in many countries around the world including Germany. Due to various methodological reasons, epidemiological studies in farming populations are more difficult to perform than among non-farmers. Major constituents of swine confinement dust include bacteria, endotoxin, mites, fungal spores, and animal dander. Gaseous pollutants include ammonia, methane, and hydrogen sulfide. In a variety of cross-sectional studies, high prevalences of respiratory symptoms and non-obstructive (and obstructive) bronchitis and Organic Dust Toxic Syndrome have been reported in pig farmers. Nasal and bronchial provocation challenges with swine confinement dust include influx of neutrophils and other inflammatory cells as well as mediators. In cross-sectional and longitudinal studies, endotoxin turns out as the probably most relevant parameter associated with lung function impairment. Further studies are clearly needed focusing on the prognosis of non-obstructive bronchitis in swine farmers and on health effects of reducing airborne contaminants in swine confinement houses.

Adolescent↗
PubMed1998

Cigarette smoking does not increase hydrogen peroxide levels in expired breath condensate of patients with stable COPD.

Cigarette smoking is the most common factor responsible for the development of chronic obstructive pulmonary disease (COPD) leading to oxidant overload in the lower airways because of the presence of oxidants in cigarette smoke and recruitment and activation of pulmonary phagocytes. In this study we intended to determine whether: 1) patients with stable COPD have higher H2O2 levels in expired breath condensate than healthy nonsmoking subjects and 2) whether cigarette smoking increases H2O2 exhalation in patients with stable COPD. The H2O2 content of the expired breath condensate of 17 healthy nonsmoking subjects and 38 patients (10 current smokers, 17 exsmokers and 11 who have never smoked) with stable COPD (forced expiratory volume in one second (FEV1) 63.3 +/- 15.5% of predicted value) was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 concentration in the expired breath condensate of COPD subjects was 10-times higher than that found in healthy controls (0.55 +/- 0.69 microM versus 0.05 +/- 0.07 microM, p < 0.005). There were no significant differences between H2O2 levels found in current smokers with COPD (0.44 +/- 0.56 microM) and COPD subjects who have never smoked (0.49 +/- 0.70 microM). No correlation was found between expired H2O2 and daily cigarette consumption or cumulative cigarette consumption in current smokers or exsmokers with COPD. These findings demonstrate that subjects with stable chronic obstructive pulmonary disease exhibit increased H2O2 generation in the airways and that cigarette smoking does not increase H2O2 production.

Breath Tests↗
PubMed1997

Polymorphonuclear leukocytes from asthmatics release more calcium from intracellular stores and have enhanced calcium increase after stimulation with N-formyl-methionyl-leucyl-phenylalanine.

Polymorphonuclear leukocytes isolated from peripheral blood of asthmatics appear to be primed to release more reactive oxygen species than cells of healthy subjects. The enhanced agonist-induced rise in the intracellular free calcium concentration may be responsible for this increased respiratory burst. To test this hypothesis we studied the N-formyl-methionyl-leucyl-phenylalanine- and cyclopiazonic acid--(an inhibitor of Ca(2+)-ATPase of intracellular calcium stores) induced calcium increase in the polymorphonuclear leukocytes of 28 subjects (16 with moderate asthma, 69.6% +/- 8.3% predicted normal peak expiratory flow and 12 normal controls) using a fluorescent probe Fura-2AM at 100 nM and 1 mM extracellular calcium concentrations. In 1 mN calcium, the N-formyl-methionyl-leucyl-phenylalanine-induced calcium increase was 1.7-fold higher in asthmatics than in healthy subjects. Similarly, the contribution of calcium from intracellular stores to the calcium response to N-formyl-methionyl-leucyl-phenylalanine was higher in asthmatics (55% +/- 14% vs. 39% +/- 14%, P < 0.01). The pool of calcium released from intracellular stores by N-formyl-methinoyl-leucyl-phenylalanine and cyclopiazonic acid was 2.3- and 2.2-fold larger than in control cells. There was a correlation between maximal intracellular calcium concentration related to N-formyl-methionyl-leucyl-phenylalanine-induced calcium release from intracellular stores and forced expiratory volume in 1 s expressed as percentage predicted and reversibility in asthmatics (r = 0.63, r = -0.53, P < 0.05). In conclusion, polymorphonuclear leukocytes of asthmatics exhibit an altered calcium response that is mainly dependent on increased calcium release from intracellular stores.

Adult↗
PubMed1997

Effect of 3 hours' passive smoke exposure in the evening on airway tone and responsiveness until next morning.

To study the effect of environmental tobacco smoke (ETS) exposure in the evening on nocturnal changes in airway tone and responsiveness, 17 subjects with mild asthma (mean +/- SD age, 26 +/- 5 years, FEV1% pred., 89 +/- 14%) were exposed to either ambient air (sham) or ETS (20 ppm CO) for 3 h (7:00 to 10:00 p.m.). Seven subjects had a history of ETS-induced respiratory symptoms. Spirometry was performed 2 h before exposure (5:00 p.m.), every 30 min during exposure, and at 11:00 p.m., 3:00 a.m., and 7:00 a.m. The provocative concentrations of methacholine necessary to decrease FEV1 by 20%, PC20FEV1, were assessed at 5:00 p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Compared with pre-exposure measurements, mean FEV1 values during and after ETS exposure were significantly lower than with sham exposure = 0.013 and 0.026). This effect, however, was due to a significant response in single individuals. The higher bronchial responsiveness after ETS than after sham exceeded one doubling concentration in 4, 5, and 4 patients at 11:00 p.m., 3:00 a.m., and 7:00 a.m., respectively. The opposite effect was observed in 2, 2, and 2 patients, respectively. There was no statistically significant mean effect of ETS on airway responsiveness during night; however, there was significant heterogeneity in individual responses (P = 0.0002). Patients with and without a history of ETS-induced symptoms did not show different responses to experimental ETS exposure. In conclusion, our data suggest that in single adult subjects with mild asthma, acute exposure to ETS in the evening can produce a deterioration of airway tone and responsiveness during the night, with wide interindividual variability in the response.

Adult↗
PubMed1997

Effect of 3 hours of passive smoke exposure in the evening on inflammatory markers in bronchoalveolar and nasal lavage fluid in subjects with mild asthma.

OBJECTIVE: The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure compared with sham (P < 0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION: In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.

Adult↗
PubMed1997

Altered intracellular calcium signalling after PAF stimulations in polymorphonuclear leukocytes from asthmatic patients.

Platelet activating factor (PAF), a potent lipid mediator, has been implicated in the pathogenesis of airways inflammation in bronchial asthma. Binding of PAF to its receptor (Nakamura et al., 1991) leads to changes of intracellular Ca2+ concentration ([Ca2+]i) that is crucial to cell activation. Therefore, the aim of our study was to investigate whether PMNL of asthmatic patients stimulated with PAF (10(-7) M) differ in relation to changes of [Ca2+]i from cells of healthy subjects. PMNL from asthmatic patients revealed attenuated first response to PAF stimulation--increase in [Ca2+]i (delta[Ca2+]i) was 1.3-fold lower in cells of asthmatics (P < 0.05) versus PMNL of healthy subjects. As determined in experiments with low extracellular calcium concentration, Ca2+ release from internal stores tended to be increased in asthmatics and hence the difference in total Ca2+ response was related to decrease in Ca2+ influx. Thus the contribution of Ca2+ from internal stores to the total first Ca2+ response upon PAF stimulation was two-fold higher (58 +/- 18 vs. 29 +/- 8%, P < 0.001) in PMNL of asthmatics compared with healthy subjects. Two subsequent Ca2+ responses evoked by stimulations with the agonist in 1 mM Ca2+ buffer did not differ between study groups. In low Ca2+ buffer PMNL of 50% of asthmatics responded to the second stimulation while cells of healthy subjects remained unresponsive. The altered Ca2+ responses in PMNL of asthmatic subjects may reflect previous contact with mediator(s) that occur in vivo which may be at least partially explained by the phenomenon of down regulation reported for PAF receptor upon cell stimulation.

Adult↗