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Biomedical subjects

C Rusznak

Publications and source records attributed to C Rusznak.

32 records · Page 2Linked to original sources
PubMed1997

The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro.

Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.

Anti-Asthmatic Agents↗
PubMed1996

Air pollutants and respiratory hypersensitivity.

Epidemiological evidence suggests that an increase in liquid petroleum derived pollutants is associated with exacerbation of allergic airway disease, and that the effects of pollution may occur 1-2 days later. Laboratory based studies have demonstrated that the pollutants responsible for the adverse effects on respiratory health include nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and respirable particulates (PM10). More recently, studies of asthmatic individuals exposed to O3, NO2 and a combination of NO2 and SO2 have indicated that these agents increase the airway responsiveness of these individuals to inhaled allergen, and that this effect may be maximal 24 h after exposure to the pollutants. Studies investigating the putative mechanisms underlying the effects of these pollutants suggest that exposure to these agents may lead to perturbation of the airway epithelium and release of pro-inflammatory mediators from the epithelial cells, which then influence the activity of inflammatory cells, such as eosinophils.

Adult↗
PubMed1996

Airway response of asthmatic subjects to inhaled allergen after exposure to pollutants.

BACKGROUND: Recent studies have suggested that air pollutants resulting from vehicle exhaust emissions and burning of fossil fuels, either in combination or individually, may enhance the airway response of asthmatic subjects to inhaled allergen. It was hypothesised that the airway response to inhaled allergen after exposure to a combination of 400 ppb nitrogen dioxide (NO2) and 200 ppb sulphur dioxide (SO2) is increased 24-48 hours after exposure. METHODS: Thirteen mild atopic asthmatic volunteers were exposed for six hours to a single exposure of air and three exposures of the combination of 400 ppb NO2 + 200 ppb SO2 in randomised order, and then challenged with increasing concentrations of Dermatophagoides pteronyssinus allergen either immediately after exposure to air, or immediately, 24 hours or 48 hours after exposure to the combination of the two pollutants, until a 20% fall in forced expiratory volume in one second (FEV1) was recorded. RESULTS: Exposure to 400 ppb NO2 + 200 ppb SO2 significantly decreased the dose of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) at all times after exposure when compared with air. The mean percentage changes in allergen PD20FEV1 immediately, 24 hours, and 48 hours after exposure to 400 ppb NO2 + 200 ppb SO2 were -37% (95% confidence intervals (CI) -50 to -23), -63% (CI -75 to -51), and -49% (CI -75 to -28.8), respectively, when compared with the PD20FEV1 after air exposure and were significant at all time points studied. The allergen PD20FEV1 at 24 hours after exposure to the combination of the two pollutants was also found to be significantly lower when compared with that immediately after exposure to the two pollutants. CONCLUSION: These results demonstrate that exposure to a combination of NO2 and SO2, at concentrations which can be encountered during episodes of increased outdoor and indoor air pollution, enhances the airway response to inhaled allergen in asthmatic subjects. This effect persists over a period of 24-48 hours and is maximal 24 hours after exposure to these air pollutants.

Adult↗
PubMed1996

Ozone-induced mediator release from human bronchial epithelial cells in vitro and the influence of nedocromil sodium.

Although animal and human studies have demonstrated that ozone inhalation leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epithelial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion molecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA). O3 exposure led to significant epithelial cell damage at concentrations of 10-500 ppb O3, as indicated by increased release of [51Cr]-labelled sodium chromate. At concentrations of 10-100 ppb, O3 induced maximal release of interleukin-8 (IL-8), granulocyte/macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and sICAM-1. The IL-8 and GM-CSF release increased significantly from 5.64+/-0.58 and 0.04+/-0.03 pg x microg(-1) cellular protein, respectively, from control cells exposed to air, to 20.16+/-2.56 and 0.20+/-0.04 pg x microg(-1) cellular protein, respectively, from cells exposed to 50 ppb O3. 10(-5) M nedocromil sodium significantly attenuated the O3-induced release of both IL-8 and GM-CSF (p<0.01). The TNF-alpha and sICAM-1 increases after exposure to 10-50 ppb O3, were also abrogated by treatment of the cells with 10(-5) M nedocromil sodium (p<0.05). Similarly, the antioxidant, glutathione, at concentrations of 400-600 microM, significantly reduced the O3-induced release of IL-8 (p<0.05). In conclusion, these studies indicate that ambient concentrations of ozone may induce airway inflammation, through release of proinflammatory mediators from airway epithelial cells. This effect may be inhibited both by the anti-inflammatory drug, nedocromil sodium, and the naturally occurring antioxidant glutathione.

Adult↗
PubMed1996

Nedocromil sodium and airway inflammation in vivo and in vitro.

We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.

Asthma↗
PubMed1994

Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation.

Air pollution may enhance the airway response of asthmatic subjects to allergen inhalation. To test the hypothesis that sulphur dioxide and nitrogen dioxide alone or in combination could have a contributory role, we have studied the effect of 6 h exposure to air, 200 parts per billion (ppb) sulphur dioxide, 400 ppb nitrogen dioxide, and the two gases together on the airway response to inhaled allergen in ten volunteers with mild atopic asthma. The subjects were exposed to the gases in random order at weekly visits, then challenged with pre-determined concentrations of Dermatophagoides pteronyssinus allergen 10 min after each exposure. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and cumulative breath units (CBU) of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) were measured after each exposure. Compared with air, neither sulphur dioxide nor nitrogen dioxide nor the combination significantly altered FEV1 or FVC. Although the decreases in PD20FEV1 after exposure to each agent alone were not significant (41.2%, p = 0.125 after nitrogen dioxide; 32.2%, p = 0.506 after sulphur dioxide) the decrease after exposure to the combination was significant (60.5 [SE 8.1]%, p = 0.015). Exposure to a combination of sulphur dioxide and nitrogen dioxide in concentrations that could be encountered in heavy traffic enhances the airway response to inhaled allergen, possibly as a result of previous airway inflammation.

Adult↗
PubMed1994

The impact of pollution on allergic disease.

Evidence suggests that allergic disease is becoming more common, particularly in industrialized societies. Two studies of schoolchildren from Aberdeen, Scotland aged 8-13 years were undertaken in 1964 and 1989 using identical questionnaires, and found that the reported prevalence of asthma had risen from 4.1% to 10.2% during this period, hay fever from 3.2% to 11.9% and eczema from 5.3% to 12%. Indication that air pollution may contribute to this increase has come from several studies. In Japan, allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. Severe asthma also occurs more commonly than mild asthma in children living in polluted areas. Exercise-induced asthma and the use of asthma medication were twice as high in a town near two power stations compared with a non-polluted town. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide. Deterioration in peak flow recordings in asthmatics and exacerbations of symptoms in hay fever sufferers correlate with ambient levels of ozone. Elucidation of the mechanisms by which exposure to air pollutants may influence the frequency of allergic disease or exacerbate symptoms has come from in vitro and in vivo experiments in animals and man. Animals exposed to ozone, sulphur dioxide, nitrogen dioxide and particles from diesel exhaust, together with allergens, show more ready development of allergic sensitization compared with those exposed to allergen alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗
PubMed1993

Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro.

Although studies of nitrogen dioxide (NO2) inhalation, in both animals and humans, have demonstrated that this agent can cause epithelial cell damage and inflammation of the airway epithelium, the mechanisms underlying these effects are not well understood. We have cultured human bronchial epithelial cells, as explant cultures from surgical tissue, and studied these firstly from their ability to constitutively synthesize specific proinflammatory cytokines and then investigated the effect of exposure to NO2 on the generation of these cytokines. Constitutive synthesis of cytokines was evaluated by analysis of both the expression of the mRNA for interleukin (IL)-1 beta, IL-4, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), by the polymerase chain reaction (PCR), and by immunocytochemical staining for the presence of cell-associated IL-1 beta, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, using specific monoclonal and polyclonal antibodies directed towards these cytokines. Release of IL-4, IL-8, GM-CSF, TNF-alpha, and IFN-gamma following exposure to 5% CO2 in air or 400 ppb and 800 ppb NO2 for 6 h was investigated by enzyme-linked immunosorbent assay. PCR demonstrated that the human bronchial epithelial cells expressed the mRNA for IL-1 beta, IL-8, GM-CSF, and TNF-alpha but not for IL-4 and IFN-gamma. Immunocytochemical staining confirmed the presence of endogenous IL-1 beta, IL-8, GM-CSF, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Human bronchial epithelial cell dysfunction following in vitro exposure to nitrogen dioxide.

Nitrogen dioxide (NO2), is a major air pollutant, that causes bronchoconstriction and bronchial hyperreactivity, and may also lead to damage and inflammation of the airway epithelium. We have cultured human bronchial epithelial cells and investigated the effect of exposure to NO2, for 20 min on epithelial cell membrane integrity and function in vitro. Epithelial cell membrane damage and permeability were assessed by release of 51Cr from prelabelled cells, and movement of 14C-labelled bovine serum albumin (BSA) across the bronchial epithelial cell monolayers. Ciliary beat frequency (CBF) of the cells was monitored by the analogue contrast enhancement technique, and arachidonic acid (AA) metabolism was investigated by analysis of radiolabelled AA metabolites generated from cultures prelabelled by incubation with [3H]-arachidonic acid. Exposure to 400 and 800 parts per billion (ppb) NO2 significantly increased the release of 51Cr from 0.9 +/- 0.4%, in control cultures exposed to 5% CO2 in air, to 9.7 +/- 3.2% and 13.9 +/- 3.5%, respectively. Similarly, NO2 also significantly increased the movement of 14C-BSA across the epithelial monolayers from 1.3 +/- 0.2%, in control cultures, to 2.7 +/- 0.2%, 3.8 +/- 0.4% and 5.1 +/- 0.5%, respectively, in cultures exposed to 100, 400 and 800 ppb NO2. Although NO2 attenuated the CBF of the cells at all concentrations investigated, this was significant only at the concentration of 2,000 ppb NO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro.

Studies investigating mechanisms of mucociliary clearance have suggested that beta 2-adrenergic agents may significantly influence ciliary activity of epithelial cells and therefore play a vital role in the maintenance of functional integrity of the airways. We have cultured human bronchial epithelial cells, from surgical explants and investigated the effects of salbutamol and salmeterol, in a time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these cells. Prior to and at several times after exposure to either salbutamol (10(-8) to 10(-3) M) or salmeterol (10(-8) to 10(-4) M), the epithelial cells were monitored for CBF and on the basis of data obtained from these studies, the effect of 10(-6) M propranolol was investigated in the presence of optimal concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a concentration of 10(-4) M and caused a transient but significant increase in the CBF from baseline level of 8.6 +/- 0.4 to 9.6 +/- 0.5 Hz (P < 0.05), after 2 h incubation. In contrast, salmeterol was maximally active at a concentration of 10(-6) M and caused a significantly rapid and prolonged increase in CBF from a baseline value of 9.2 +/- 0.4 to 10.9 +/- 0.6 Hz (P < 0.02) and 10.6 +/- 0.8 Hz (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10(-6) M) abrogated the salbutamol- but not the salmeterol-induced increases in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1992

The effect of human eosinophils on cultured human nasal epithelial cell activity and the influence of nedocromil sodium in vitro.

Although there is increasing evidence of a pathogenic role for eosinophils in the airway epithelium, there is little direct evidence which demonstrates that eosinophils influence epithelial cell activity in humans. We have cultured human nasal epithelial cells in vitro and studied the effect of isolated human eosinophils on the ciliary beat frequency (CBF) and cell membrane integrity of these cells after incubation in the absence or presence of 0.1 microM phorbol 12-myristate 13-acetate (PMA) or 0.1 mg/ml opsonized latex beads and the absence or presence of 10(-5) M nedocromil sodium. CBF was monitored by an analogue contrast-enhancement technique, and cell damage was assessed by release of 51Cr from the cells. Cell cultures were also assessed for the percentage of eosinophil cationic protein (ECP) released into the medium at the end of incubation. Neither 0.1 microM PMA, 0.1 mg/ml opsonized latex beads, 10(-5) M nedocromil sodium, nor eosinophils alone altered the CBF of the epithelial cells. PMA-stimulated eosinophils, however, attenuated the CBF significantly, from 10.2 +/- 0.3 to 8.8 +/- 0.4 Hz (P less than 0.05) after 15 h of incubation. Similarly, opsonized latex bead-stimulated eosinophils led to a significant attenuation of CBF from 9.2 +/- 0.3 to 8.4 +/- 0.3 Hz (P less than 0.05), 6.9 +/- 0.5 Hz (P less than 0.001), and 7.5 +/- 0.3 Hz (P less than 0.001) after 2, 15, and 24 h of incubation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗