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Biomedical subjects

A Gillissen

Publications and source records attributed to A Gillissen.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Successful treatment of chronic necrotizing pulmonary aspergillosis with oral itraconazole long-term therapy].

HISTORY AND ADMISSION FINDINGS: A 66-year-old man with bullous pulmonary emphysema, was being treated with oral prednisone, had over the previous two month experienced dyspnoea, productive cough and an 8 kg weight loss. Physical examination revealed inspiratory rales over the right middle lobe, with faint vesicular breathing in the other lobes. INVESTIGATIONS: Inflammation parameters were markedly elevated (WBC 24,800/microliter, C-reactive protein 28.6 mg/dl), while the chest radiograph showed liquid infiltrates in the right upper and middle lobes. Despite administration of antibiotics the infiltrates persisted. Aspergillus fumigatus was demonstrated in bronchial secretion. TREATMENT AND COURSE: Antifungal treatment with itraconazole (400 mg/d) was started and resulted in marked subjective improvement, normalization of the inflammation parameters and slow regression of the pulmonary infiltrates. Thoracic computed tomography one year later merely revealed residual post-inflammatory changes. CONCLUSION: An insidious course and treatment-resistant lung infiltrates in patients with steroid treatment should suggest chronic necrotizing pulmonary aspergillosis and this pathogen should be looked for in bronchial secretions. Antifungal treatment with itraconazole is essential and efficacious.

Administration, Oral↗
PubMed1999

[Pulmonary aspergillosis in patients without pre-existing pulmonary disease after brain edema prevention with dexamethasone].

Pulmonary aspergillosis (PA) is a well-described complication in severely immunocompromised hosts. We report on one case of invasive PA and one case of PA following oral dexamethasone prophylaxis for cerebral oedema. Steroids were administered in a dosage of 14 mg and 16 mg, daily respectively for 21 and 15 days. Both patients died despite antifungal treatment. We conclude that PA must be considered as a cause for pulmonary complications in non-immunosuppressed, non-neutropenic patients during oral dexamethasone prophylaxis for neurological disease.

Aged↗
PubMed1998

Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure.

Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.

Asbestos, Crocidolite↗
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

Crocidolite asbestos causes an induction of p53 and apoptosis in cultured A-549 lung carcinoma cells.

A number of genotoxic chemicals and agents, such as benzo(a)pyrene and ultraviolet light, are able to induce nuclear accumulation of p53 protein. Usually, this response is transient and a consequence of stabilization of the wild-type p53 protein. After withdrawal of the exposure, the amount of p53 protein returns to a normal level within hours or a few days. We have studied the p53 response to the exposure of crocidolite asbestos in A-549 lung carcinoma cells using three different methods, i.e., p53 immunohistochemistry, Western blotting and metabolic labelling followed by p53 immunoprecipitation. With these techniques we demonstrate a dose-dependent p53 nuclear response to crocidolite exposure. The half-life of p53 protein in A-549 lung carcinoma cells cultured in serum-free media increased from 30 up to 80 min, and the protein reacted with a wild-type specific antibody suggesting that it was in a wild-type conformation. In situ 3'-end labelling of A-549 cells demonstrated a dose-dependent increase in apoptotic activity. Our data support the idea that increased apoptotic activity, induced by crocidolite, is mediated by p53.

Journal Article↗
PubMed1997

Oxidant scavenger function of ambroxol in vitro: a comparison with N-acetylcysteine.

Highly reactive oxygen metabolites play an important role in inflammatory processes in the lung. Ambroxol (2-amino-3,5-dibromo-N-[trans-4- hydroxycyclohexyl]benzylamine) has been shown to reduce oxidant-mediated cell damage. However, the mechanism of this effect remains unclear. In order to evaluate oxidant scavenger function increasing concentrations of ambroxol (0-10(-3) mol/l) were compared with equimolar concentrations of N-acetylcysteine (NAC) and glutathione (GSH) in vitro to reduce OH. (hydroxyl radical), HOC1 (hypochlorous acid), O-2 (superoxide anion) and H2O2 (hydrogen peroxide). OH. was measured spectrophotometrically (deoxyribose assay); O-2 (xanthine/x-oxidase), H2O2 and HOC1 (HOC1/OC1-) were determined by chemiluminescence. Ambroxol, NAC and reduced GSH scavenged OH. significantly at 10(-3) mol/l, while HOC1 was inhibited at concentrations > or = 10(-4) mol/l completely (P < 0.01). NAC and GSH had no anti-O-2 function, while ambroxol (10(-4) mol/l) reduced O-2 by 14.3 +/- 6.7%. In contrast, GSH and NAC scavenged H2O2 at > 10(-6) mol/l (P < 0.01), while ambroxol had no anti-H2O2 effect. Our data demonstrate direct oxidant-reducing capabilities of ambroxol, which may be directly related to the aromatic moiety of the molecule. However, high concentrations (micromolar concentrations) are needed. Due to differences in direct oxidant scavenger function, a combination of ambroxol and NAC could be beneficial in antioxidant therapy.

Acetylcysteine↗
PubMed1997

Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in vitro.

This study quantifies the antioxidant function of ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine) in vitro. Polymorphonuclear cells (PMN) and mononuclear cells were isolated from the blood of healthy volunteers (n = 46) to determine reactive oxygen species (ROS) by luminol-enhanced chemiluminescence. Ambroxol or the controls N-acetylcysteine (NAC), nacystelyn (NAL), glutathione (GSH), superoxide dismutase (SOD), catalase, and the combination of SOD/catalase were incubated for 1 or 2 h with zymosan-activated cells in vitro using concentrations ranging from 10(-6) to 10(-3) mol/liter. Reduction of ROS-mediated luminescence was similar within the cell types. Ambroxol (10(-4) mol/liter) reduced ROS about 75% (1-h incubation) and 98% (2-h incubation), respectively (p < 0.001). SOD and SOD/catalase, but not the H2O2-catalyzing substances (NAC, NAL, GSH, and catalase), reduced cellular ROS. This indicates that inflammatory cells predominantly generate O2-, which can be scavenged by ambroxol. The antioxidant function of ambroxol with increasing incubation time suggests additional cellular antiinflammatory properties of this substance. Our results indicate that good antioxidant function of ambroxol is related mainly to direct scavenger function of reactive oxygen metabolites such as O2-. However, an antioxidative effect of ambroxol may also be associated with the reduction of prooxidative metabolism in inflammatory cells. Concluding from this observation, and because of the well known high affinity of ambroxol for lung tissue, ambroxol may be an alternative in antioxidant augmentation therapy, particularly in pulmonary diseases characterized by an overburden of toxic oxygen metabolites.

Acetylcysteine↗