Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.     

Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness

OBJECTIVE: Major depression is associated with defective antioxidant defenses. Vitamin E is the major fat soluble antioxidant in the body. The aim of the present study is to examine serum vitamin E concentrations in major depressed patients versus normal volunteers. METHOD: Serum vitamin E concentrations were measured in 26 healthy volunteers and 42 major depressed patients by means of HPLC. Since vitamin E is a fat soluble vitamin, and serum vitamin E concentrations are strongly related to these of low-density-lipoprotein cholesterol (LDL-C) and triglycerides, we have adjusted the results for possible differences in these lipids. The numbers of peripheral blood leukocytes were measured. RESULTS: Patients with major depression had significantly lower serum vitamin E concentrations than healthy controls. The area under the ROC (receiver operating characteristics) curve was 83%. There were significant and negative correlations between serum vitamin E and number of total leukocytes and neutrophils. CONCLUSIONS: Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression.     

Identification and characterization of human pulmonary dendritic cells

Dendritic cells (DC) are specialized antigen-presenting cells, linking innate and adaptive immune responses, and thus play an important role in immunologically mediated diseases, including pulmonary diseases such as asthma and respiratory viral infections. Although much is known about the characteristics of lung DC in animal models, very few data concerning human lung DC are available. The goal of our study was to identify and characterize dendritic cells in human lung by preparing single-cell suspensions from surgical resection specimens and subsequent labeling with the recently developed blood dendritic cell antigen (BDCA) markers. A straightforward isolation procedure was developed to avoid phenotypical and functional changes induced by extensive purification methods. In this way, human lung DC were directly identified without the need for an additional adherence step for further purification. For the first time, we demonstrate the presence of three previously unidentified DC subsets in human lung digests: myeloid DC type 1 (BDCA1+/HLA-DR+), myeloid DC type 2 (BDCA3+/HLA-DR+), and plasmacytoid DC (BDCA2+/CD123+). The presence of CD1a+ DC in the human lung was confirmed. The identification and characterization of different human pulmonary DC subtypes is of great importance for the future development of DC-based immunotherapies.     

Effect of bronchodilation on regional lung function measured by 133Xe and gamma camera

Using ¹³³Xe, a gamma camera and off-line data handling the effect of inhaled Salbutamol on regional lung function was measured in six patients with chronic obstructive lung disease and associated bronchospasm.After bronchodilation only minor changes were obtained in regional ventilation or in the arterial hypoxemia, although the overall airways obstruction improved markedly. These findings suggest that the bronchodilating agent had an effect mainly on the larger airways and almost did not influence the function of the more peripheral lung units responsible for gas exchange. Also, a slight but direct effect on the perfusion was demonstrated. The effect on the ¹³³Xe ventilation-perfusion ratio was not correlated with that on the hypoxemia, indicating that the first is not a good representation of the latter.Supported by a grant from the Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

Preoperative and postoperative abnormalities in chest x-ray indices and in lung function in pectus deformities

In 88 patients with pectus deformities radiologic chest indices and routine pulmonary function tests were measured before and 1 to 20 years after corrective surgery. A combination of anteroposterior indices at the upper and lower level of the chest were investigated to quantitate and to discriminate the different pectus deformities. The study comprised four groups: pectus excavatum, pectus carinatum, pectus deformatum and pectus excavatum with scoliosis. These indices were also assessed in 250 healthy males and females. Generally, several indices showed significant and discriminative changes in the different patient groups and improved again after surgery. Preoperative lung function was decreased in pectus excavatum only. In all groups lung function worsened after surgery. A stepwise discriminant analysis performed on the large group with pectus excavatum indicated that postoperative lung function was decreased if the preoperative value of FEV1 or VC was more than about 75 percent predicted and vice versa, but that it was not related to other factors such as radiologic indices, age at operation or time since operation.     

Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders

We report the results of a prospective registration of the prevalence of interstitial lung diseases by 20 centres of respiratory medicine in Flanders from January 1992 till July 1996. The 20 centres registered a total of 362 cases. Sarcoidosis (31% with inclusion of stage I, or 22% without stage I), idiopathic pulmonary fibrosis (20%), hypersensitivity pneumonitis (13%) and unclassified forms of interstitial lung diseases (9%) were the most often diagnosed diseases. The mean age of the patients was 52 +/- 17 (SD) years, but ranged from 32 +/- 10 years in histiocytosis X to 70 +/- 13 years in drug induced interstitial lung diseases. The male to female ratio was 1.3 but ranged from 2.3 in interstitial lung diseases due to inhalation of inorganic materials to 0.8 in interstitial lung diseases due to connective tissue disease. The diagnosis was considered certain in 60%, probable in 30% and possible in 10%. In 50% of the cases the diagnosis was proven by biopsy and the most often used biopsy technique was transbronchiolo-alveolar biopsy (40% of biopsies) followed by open lung biopsy (32%). At diagnosis vital capacity was 82 +/- 22% pred. (ranging from 92 +/- 19% in sarcoidosis to 71 +/- 24% in idiopathic pulmonary fibrosis) and CO-diffusing capacity was 77 +/- 19% pred. (ranging from 77 +/- 19% in sarcoidosis to 41 +/- 13% in drug induced pneumonitis). The regional frequency of interstitial lung diseases in Flanders varied widely and was not proportional to the regional distribution of the 20 contributing centres. In conclusion this registration provides interesting information on the occurrence and presentation of the different forms of interstitial lung diseases, although it may still underestimate the real prevalence and incidence of interstitial lung diseases.     

Evaluation of the safety and efficacy of amrinone in chronic obstructive lung disease with cor pulmonale

In a pilot study the effect of a bolus dose of amrinone intravenously (IV), 0.5 or 1 mg/kg body weight, in 10 patients with chronic obstructive lung disease and cor pulmonale was evaluated. We found that the higher dose of 1.0 mg/kg IV significantly (P less than 0.05) decreased the mean pulmonary artery pressure and pulmonary wedge pressure without significant changes in cardiac output, in systemic blood pressure or in arterial blood gas values. No adverse effects were recorded in any of the patients.     

Total respiratory resistance and reactance in patients with diffuse interstitial lung disease

In 54 patients with interstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, diffusing capacity (DLCO), total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of the forced oscillation technique. In all patients DLCO was less than 75% of the expected value. Patients were classified into two groups depending on total lung capacity (TLC): group A with TLC less than 80% of expected, and group B with TLC of 80% or more. Group A demonstrated a decrease of Xrs especially at low frequencies, with small, not significant changes in Rrs. In the patients in this group with the lowest values of TLC (less than 50%), we observed an increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function data and forced oscillation parameters, showed tight correlations between TLC in absolute value or VC in percent of the predicted value on the one hand and average level of Xrs and average slope of Xrs (and Rrs) vs frequency curves on the other hand. Measurements of lung mechanics in five additional patients and comparison with a model of the respiratory system suggest that the changes of Rrs and Xrs are not explained totally by the observed increase in lung tissue resistance and decrease in lung compliance. The observed changes in Rrs and Xrs are not specific for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases.