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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

At least 109 records · Page 6Linked to original sources
PubMed1999

N-acetylcysteine and ambroxol inhibit endotoxin-induced phagocyte accumulation in rat lungs.

UNLABELLED: We have investigated whether pretreatment with N-acetylcysteine (NAC) and/or ambroxol (Amb), drugs known as reactive oxygen species (ROS) scavengers, would minimize lipopolysaccharide (LPS)-induced leucocyte accumulation in rat lung microvasculature and protect lungs from damage and the effect of these drugs on chemotactic peptide (fMLP)-induced chemiluminescence of human polymorphonuclear leukocytes (PMNs). Animals were injected ip with NAC (27.6 mg/kg, n=8), ambroxol (70 mg/kg, n=8), combination NAC+ambroxol (n=8), or 1 ml buffer alone (n=8), once a day for 3 consecutive days. Then animals were injected with LPS (17 mg/kg), and killed 3 h later. In each of another four groups eight rats were used as a control, and received the same drug treatment but LPS was replaced with 0.9% NaCl. PMNs and macrophages (Ms) were counted in histologic slides of lung tissue. Using computer image analysis we measured the area of alveolar profiles. Luminol-enhanced chemiluminescence was measured in PMNs suspensions obtained from healthy volunteers. Chemiluminescence intensity was measured in resting and fMLP-stimulated cells, and compared between cells incubated with Amb, NAC or distilled water. We observed significant differences in the number of PMNs and Ms, alveolar profile area between control and LPS-treated animals (P<0.01). PMNs and Ms were numerous in lungs of LPS-administered animals (PMNs: Median (M)=137.5 per 6 high power fields range (r)=54.0; Ms: M=123.0 r=11.0), less numerous in ambroxol-treated group (PMNs: M=101.5 r=32.0 and Ms:53.5 r=36.0), not abundant in NAC (PMNs:M=56.0 r=28.0 and Ms:M=20.5 r=13.0) and in NAC+ambroxol treated rats (PMNs:M=53.5 r=21.0 and Ms:M=29.0 r=9.0), and rare in LPS+drugs-untreated control group (PMNs:M=40.5 r=19.0 and Ms:M=18.5 r=15.0). Chemiluminescence assay revealed that 100 micro;M ambroxol stimulated fMLP-induced PMNs chemiluminescence and NAC of the same concentration had no significant effect. CONCLUSION: In our experiment we showed that pretreatment with NAC and ambroxol may inhibit phagocyte influx to rat lung and may protect it from damage. We also revealed that NAC at dose 27.6 mg/kg has stronger protective properties than ambroxol at dose 70 mg/kg and this may result from enhancing effect of ambroxol on fMLP-provoked PMNs chemiluminescence.

Acetylcysteine↗
PubMed1999

Grip forces exerted against stationary held objects during gravity changes.

In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object's weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object's weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.

Adult↗
PubMed1999

Respiratory health and fluoride exposure in different parts of the modern primary aluminum industry.

OBJECTIVE: The aim of this cross-sectional study was to investigate possible acute and long-term respiratory health effects of work at different working places in the primary aluminum industry. METHOD: A cross-sectional study was carried out on 78 potroom workers, 24 foundry workers, and 45 carbon-plant workers (n = 147, exposed group), and 56 control workers (watchmen, craftsmen, office workers, laboratory employees) of a modern German prebake aluminum plant. The survey consisted of pre- and postshift spirometric and urinary fluoride measurements. RESULTS: Potroom workers had significantly lower preshift results with regard to forced vital capacity (FVC, 99. 5% versus the 107.2% predicted; P < 0.05) and peak expiratory flow (PEF, 85.2% versus the 98.4% predicted; P < 0.01) as compared with controls. In a multiple regression model a small but significant negative correlation was found between postshift urinary fluoride concentrations and FVC, FEV(1), and PEF. Across-shift spirometric changes were observed only in FVC among carbon-plant workers (103.0 +/- 13.3% predicted preshift value versus 101.2 +/- 13.6% predicted postshift value; P < 0.05). CONCLUSIONS: The results suggest that lung function impairment in the modern primary aluminum industry may be only partly due to fluoride exposure and that working in aluminum carbon plants may cause acute lung function changes.

Adult↗
PubMed1999

Increased serum concentrations of conjugated diens and malondialdehyde in patients with pulmonary tuberculosis.

During pulmonary inflammation increased amounts of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI) are produced as a consequence of phagocyte respiratory burst. One of the manifestation of these free radical-mediated processes is lipid peroxidation (LP). The aim of our study was to assess the concentration of lipid peroxidation products (LPPs), conjugated diens (CD) and malondialdehyde (MDA), in patients with active TB. Forty-two patients were enrolled into the study. Half (group I) had advanced TB and were sputum smear-positive. The remainder (group II) had only small radiographical changes and were sputum smear-negative. Serum concentrations of CD and MDA were measured at days 0, 7, 14 and 28 in group I and day 0 in group II. We found that in all patients with active TB CCD (1.0 +/- 0.05A233) and CMDA (2.01 +/- 0.16 nmol dl-1) were significantly elevated compared to healthy controls (0.67 +/- 0.03A233 and 1.36 +/- 0.08 nmol dl-1, respectively) (P < 0.001). The highest levels of LPPs were in patients with advanced TB. These concentrations were stable during the first month of anti-tuberculous therapy. Our data indicated that, as in bacterial pneumonia, LPPs were enhanced in active TB. The levels of LPPs depended on the form of the disease as they were higher in subjects with advanced disease than in those with only small radiographical changes. Further studies are needed to assess the role of antioxidants as adjuvant therapy in patients with pulmonary TB.

Biomarkers↗
PubMed1999

Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: no significant effect of cigarette smoking.

The imbalance between oxidants and antioxidants is known to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most frequent factor responsible for development of COPD by leading to oxidant overload in the lower airways, due to presence of its own oxidants and to recruitment and activation of pulmonary phagocytes. We aimed to determine whether (1) patients with stable COPD have higher thiobarbituric acid-reactive substances (TBARs, an end-product of lipid peroxidation) and H2O2 levels in expired breath condensate than healthy subjects who have never smoked; (2) COPD subjects who are current smokers exhale more TBARs and H2O2 than COPD ex-smokers and those who have never smoked; and (3) concentration of TBARs correlates with H2O2 levels in the breath condensate of COPD patients. The TBAR and H2O2 content in expired breath condensate of 17 healthy nonsmoking subjects and 44 patients (11 current smokers, 20 ex-smokers and 13 who had never smoked) with stable COPD [forced expiratory volume in 1 s (FEV1) 63.3 +/- 16.3% and FEV1 reversibility 5.2 +/- 4.3% predicted value] was measured spectrofluorimetrically by the thiobarbituric acid and homovanillic acid methods, respectively. The mean concentrations of TBARs and H2O2 in the expired breath condensate of COPD subjects were 12 (0.48-0.86 microM vs. 0.04 +/- 0.14 microM; P < 0.05) and 10 times (0.48 +/- 0.67 microM vs. 0.05 +/- 0.07 microM; P < 0.005) higher than in healthy controls. Current smokers with COPD did not exhale more H2O2 than COPD ex-smokers and those who had never smoked. TBARs levels shared only a tendency to be higher in the breath condensate of smoking COPD subjects than in that of ex-smokers (0.92 +/- 1.49 microM vs. 0.35 +/- 0.44 microM) and of COPD subjects who had never smoked (0.92 +/- 1.49 microM vs. 0.30 +/- 0.53 microM). No correlation was found between TBAR and H2O2 levels in the whole COPD group. These variables did not correlate with cigarette smoking status and the time from smoking cessation. Subjects with stable COPD exhibit increased lipid peroxidation and H2O2 generation in the airways. Current cigarette smoking does not distinguish COPD subjects with respect to TBARs and H2O2 exhalation.

Antioxidants↗
PubMed1999

Variations of p53 in cultured fibroblasts of patients with lung cancer who have a presumed genetic predisposition.

The authors studied cultured skin fibroblasts of 64 patients with lung cancer for constitutive mutations of the p53 tumor suppressor gene by using polymerase chain reaction and single-strand conformation polymorphism covering the entire coding region. The patients were considered to be genetically predisposed because lung cancer had developed in 25 of them before age 46 and because 42 of them had at least one first-degree relative with lung cancer. One mutation was detected at position 235 coding for serine instead of asparagine in the conserved DNA binding domain. The Pro/Pro genotype at codon 72 of p53, considered to harbor an increased risk for lung cancer, could not be detected with increased frequency in this study's patients. From these data, the authors conclude that constitutive variations of the p53 gene do not represent a major genetic determinant for lung cancer.

Adult↗
PubMed1999

Lack of combined effects of exposure and smoking on respiratory health in aluminium potroom workers.

OBJECTIVE: To investigate the combined influence on respiratory health of smoking and exposure in an aluminium potroom. METHODS: In a cross sectional study of 75 potroom workers (23 never smokers, 38 current smokers, 14 ex-smokers) and 56 controls in the same plant (watchmen, craftsmen, office workers, laboratory employees; 18 non-smokers, 21 current smokers, 17 ex-smokers), prevalences of respiratory symptoms and spirometric indices were compared. RESULTS: Smokers in the potroom group had a lower prevalence of respiratory symptoms than never smokers or ex-smokers, which was significant for wheezing (2.6% v 17.4% and 28.6% respectively, both p < 0.01), whereas respiratory symptoms in controls tended to be highest in smokers (NS). No effects of potroom work on the prevalence of respiratory symptoms could be detected. In potroom workers, impairment of lung function due to occupational exposure was found only in non-smokers, with lower results for forced vital capacity (FVC) (98.8% predicted), forced expiratory volume in one second (FEV1) (96.1% predicted) and peak expiratory flow (PEF) (80.2% predicted) compared with controls (114.2, 109.9, and 105.9% predicted; each p < 0.001). Conversely, effects of smoking on lung function were only detectable in non-exposed controls (current smokers v non-smokers: FVC 98.8% v 114.2% predicted; p < 0.01; FEV1 95.5 v 109.9% predicted; p < 0.05). CONCLUSIONS: In a cross sectional survey such as this, the effects of both smoking and occupational exposure on respiratory health may be masked in subjects with both risk factors. This is probably due to strong selection processes which result in least susceptible subjects continuing to smoke and working in an atmosphere with respiratory irritants.

Adult↗
PubMed1999

Hydrogen peroxide in expired air condensate correlates positively with early steps of peripheral neutrophil activation in asthmatic patients.

We have found an increased H2O2 level in expired air of asthmatic patients. Neutrophils from these subjects generated higher amounts of superoxide radicals after challenge with phorbol esters than those from healthy subjects which may result from an increased activity of NADPH-oxidase. The enhanced Ca2+ mobilisation in neutrophils from asthmatics could be responsible for increased production and subsequent elevated H2O2 concentration in expired breath condensate. In this study we wished to determine whether neutrophils of asthmatic patients have enhanced [Ca2+]i response after N-formyl-methionyl-leucyl-phenylalanine--fMLP challenge as compared with cells from healthy donors, and if so, does it correlate with H2O2 levels in expired air. We examined 21 patients, 10 healthy individuals as a control group (mean age 34.3 +/- 5.5, 6 males and 4 females) and 11 asthmatic subjects (mean age 38.2 +/- 7.2, 7 males and 4 females). The rise of [Ca2+]i as an early event of neutrophil activation, was measured spectrofluorimetically with Fura-2-AM. The mean H2O2 level, measured spectrofluorimetrically in the expired breath of asthmatics, was 20-fold higher than that in healthy control (0.18 +/- 0.20 vs. 0.01 +/- 0.04 microM, p < 0.05). [Ca2+]i increase after challenge by fMLP (delta [Ca2+]i) was much higher in asthmatics than in control group (205.0 +/- 44 vs. 113.0 +/- 22 nM, p < 0.05, respectively). A strong correlation was observed between H2O2 and delta [Ca2+]i and maximal velocity of increase in [Ca2+]i in asthmatics (r = 0.87, p < 0.01 and r = 0.64, p < 0.05). We conclude that elevated H2O2 level in the expired breath condensate of asthmatics can be generated by activated neutrophils in the course of mucosal inflammation observed in bronchial asthma.

Adult↗
PubMed1999

Clinical utility of a commercial ligase chain reaction kit for the diagnosis of smear-negative pulmonary tuberculosis.

SETTING: In paucibacillary forms of smear-negative tuberculosis it is very difficult to establish a correct and rapid diagnosis, as several weeks are usually required to obtain positive results from culture. In the last few years new rapid techniques based on molecular biology for the detection of Mycobacterium tuberculosis have been introduced. OBJECTIVE: The aim of this study was to evaluate the utility of the ligase chain reaction method (LCx, Abbott) for the diagnosis of smear-negative pulmonary tuberculosis. DESIGN: Thirty smear-negative patients with radiographic changes and clinical signs consistent with TB participated in the study. Sputum and bronchial aspirate were assessed according to traditional methods on Löwenstein-Jensen medium, and bronchoalveolar lavage (BAL) was assessed by the LCx test and the Bactec 460 system. Another 30 patients with non-tuberculous infections were included in the study as controls. RESULTS: Of the 30 patients suspected of tuberculosis, 19 had active disease on clinical, bacteriological and radiographic grounds, nine inactive tuberculosis and two had lung cancer. Bacteriological confirmation was obtained in 12 of the 19 (63.2%) patients with active tuberculosis. The sensitivity of sputum culture was 42.1% and bronchial aspirate culture 47.4%. BAL fluid revealed positive results in 57.9% using both LCx and Bactec. The results of the LCx assay can be obtained in 5 hours as opposed to several weeks using other methods. CONCLUSION: The LCx test may be useful in the diagnosis of smear-negative pulmonary tuberculosis and may be recommended in these clinical situations.

Adult↗
PubMed1999

Identification of actin from hepatoma Morris 5123 cells.

The hepatoma Morris 5123 tumor growth is accompanied by changes in actin content and polymerization (Malicka-Błaszkiewicz et al. (1995) Mat. Med. Pol., 27, 115-118; Nowak et al. (1995) J. Exp. Cancer Res. 14, 37-40). Presently actin isoforms from cytosol and cytoskeleton fractions were separated by SDS/PAGE and identified with antibodies directed against different actin isoforms. Actin isolated from the cytosol by affinity chromatography on DNase I bound to agarose shows the presence of only one protein spot on 2D gel electrophoresis corresponding to the mobility of the rabbit a skeletal muscle actin (Mr 43,000) and isoelectric point equal to 5.3. It interacts only with monoclonal anti beta actin isoform antibodies, posing the question of differential affinity of actin isoforms to DNase I.

Actins↗
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↗