Bulletin europeen de physiopathologie respiratoire最新文献

The toxicological implications of the formation of active oxygen species have attracted growing interest in recent years. Under aerobic conditions, oxygen radicals are normal cellular metabolites. However, the production of oxygen radicals may be greatly stimulated in the presence of various redox active compounds. Eventually, the stimulation of oxygen radical production may be so great as to overwhelm the cellular defence systems, create an oxidative stress and bring about toxicity. Recent studies in this laboratory indicate that glutathione and protein thiol depletion play a critical role in the development of oxidative cell injury. This depletion of cellular thiols can result in a disturbance of intracellular calcium ion homeostasis, which seems to be directly related to cell killing.

The lung is particularly exposed to oxidant stresses, such as those that can be brought about by oxygen-derived free radicals. They mainly result from the monovalent reduction of molecular oxygen. The most reactive oxygen metabolite is the hydroxyl radical, whose formation appears to be dependent upon the presence of iron-chelates. Free radicals are normally produced by cellular metabolism. Furthermore, activated phagocytes, during the 'respiratory burst', release oxygen metabolites that are necessary for bacterial killing. Free radicals are highly reactive species. Their target molecules are proteins, DNA and polyunsaturated fatty acids whose alterations can lead to cell death. There are, however, several antioxidant substances which are enzymatic (superoxide dismutases, catalase and glutathione peroxidase) and non enzymatic (reduced glutathione, vitamin E and C etc...). In many experimental systems, an increase in antioxidant defences is associated with higher resistance to oxidant stress. However, the antioxidant system may be overwhelmed by an overproduction of intra and/or extracellular free radicals leading to tissue injury. Recent advances in the understanding of free radical metabolism can suggest some new therapeutic approaches such as the administration of exogenous antioxidant or iron chelators.

The object of the study was to find a model to summarize all the information from dose-response curves, by determining the coefficients to be used to compare groups of subjects. Three coefficients were calculated from the following model: F(d)/F(o) = ONE - k(d-delta)alpha+, where F(d)/F(o) was the ratio between FEV1 at dose (d) of methacholine and prechallenge FEV1, 'k' the slope of the relative variation of FEV1 with the dose, 'delta' the threshold dose and 'alpha' a shape factor. The model was applied to the study of hyperresponsiveness in a population of 317 men. The results illustrated the interest of this model which was applicable to 91% of the population and permitted fine discrimination of the groups studied.

Oxidants are generated in vivo by multiple mechanisms, including stimulation of leukocytes, hyperoxia, metabolism of arachidonic acid, and the activation of various oxidases. When the biochemical defences to the oxidants are inadequate, injury of tissues results. This injury was observed in rabbits and rhesus monkeys when pulmonary inflammation was induced with phorbol esters or formylated peptide given intrabronchially. We have recently investigated metabolic changes in various cells exposed to oxidants that are generated from stimulated leukocytes, including H2O2, O2, and HOCl. The target cells used were P388D1 murine macrophage-like tumour cells, human peripheral lymphocytes, GM 1380 human fibroblasts and rabbit alveolar macrophages. The oxidants used were H2O2 and PMA stimulated PMNs or neutroplasts. Lysis could only be prevented when catalase was added within the first 30-40 min of H2O2 exposure indicating that early metabolic changes determined the fate of the cell. Within seconds after the addition of H2O2 to P388D1 cells activation of the hexose monophosphate shunt (HMPS) was observed indicative of increased glutathione cycle activity. At the same time DNA strand breaks (determined by an alkaline unwinding technique) were detected. They resulted in the activation of the DNA repair enzyme poly-ADP-ribose polymerase (pADP-RP) within minutes after the addition of H2O2. At the same time ATP and NAD (the substrate of pADP-RP) concentrations dropped and nicotinamide accumulated extracellularly. 10-15 min after oxidant exposure free intracellular Ca++ concentrations determined by Quin 2 fluorescence started to increase due to release from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been hypothesized that naloxone may alter the ventilation-perfusion relationship in patients with chronic obstructive pulmonary disease (COPD) with associated respiratory failure, through the release of hypoxic pulmonary vasoconstriction. To investigate the effects of naloxone on gas exchange, seven clinically stable patients with severe COPD (type B) (forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 38.3 +/- 4.0%) with hypoxaemia and hypercapnia (PaO2 7.6 +/- 0.4 kPa; PaCO2 6.4 +/- 0.3; pH 7.37 +/- 0.02), aged 59.0 +/- 4.6 yr, were studied. Breathing patterns, haemodynamic and conventional and inert gas exchange measurements were made while breathing room air before, during and 60 min after i.v. naloxone infusion. Naloxone and catecholamine plasma levels were also determined. In three subjects (protocol A), measurements were made using increasing concentrations of naloxone (cumulative dose: 54 mg), while the remaining four patients were studied (protocol B) at a fixed concentration of naloxone (cumulative dose: 38 mg). Despite high levels of naloxone (up to 150 ng.ml-1), no significant differences from baseline were observed in any of the measurements, during or after infusion. It is concluded that i.v. naloxone given as described has no effects on pulmonary gas exchange in clinically stable COPD patients with chronic respiratory failure.

We recorded the lung sound and flow rate from six normal subjects (3 male and 3 female). Sound was picked up at the trachea with a sensitive microphone held in a small probe. Flow rate was measured at the mouth using a Fleisch No. 3 pneumotachograph. Subjects were made to breath for 15 s, with an increasing peak flow rate starting from apnoea to around 2 l.s-1. Both sound and flow rate were directly digitized (i.e. without temporary analogic recording) at a sampling rate of 5120 Hz. Sound and flow were then divided in 128-sample blocks. For each block, the frequency spectrum was computed using the fast Fourier transform. Frequency spectrum depends on the flow rate in many ways. We computed the following formula on each spectrum: D = K.Fmean/(1 + A/Amean) where K and A are constant, Fmean and Amean are respectively the mean frequency and the mean amplitude of the spectrum computed on a 128-sample block. D may be considered as an evaluation of the flow rate every 50 ms. Plotted versus the measured values of the flow rate, D showed a linear relationship. This feature can be used as an almost instantaneous evaluation of the flow rate, or it is possible to compute the mean of D over consecutive 128-sample blocks. This has lead us to calculate the mean of the flow rate over 100, 200, ..., 800 ms. Of course, the longer the time window, the better the correlation between computed flow and real value. The values obtained for this correlation varied between 0.79 and 0.94.

We studied the effects of local high frequency mechanical vibration on ventilatory (VE) and occlusion pressure (P0.1) responses to CO2 rebreathing in twelve normal subjects. Three kinds of vibration procedures were employed: a) sustained vibration over the tendon of the quadriceps femoris near the knee, b) sustained vibration of the right 2nd or 3rd parasternal intercostal spaces and c) 'in-phase' chest wall vibration applied during inspiration on the right 2nd or 3rd parasternal intercostal spaces and during expiration on the right 9th or 10th intercostal spaces anterior to the midaxillary line. The slopes of VE response to hypercapnia (delta VE/delta PETCO2) were 2.05 +/- 0.26 (mean +/- SE), 2.48 +/- 0.24, 2.82 +/- 0.32 and 3.35 +/- 0.38 l.min-1/mmHg in the control state, during tendon vibration of quadriceps femoris, sustained chest wall vibration and 'in-phase' chest wall vibration, respectively. This sequential increase in slopes was significant compared to the control values. The effect of vibration on the P0.1 response to hypercapnia was similar to that of VE. We conclude that local mechanical vibration facilitates responsiveness to hypercapnia.

Rheumatoid arthritis (RA) is a generalized disorder characterized by chronic inflammation of peripheral joints and by involvement of many organs, including the lung parenchyma. The inflammatory infiltrates of the rheumatoid synovial membranes are associated with increased numbers of T-lymphocytes, with increased proportions of helper (OKT4 positive) T-cells and decreased percentages of suppressor/cytotoxic (OKT8 positive) T-cells, and since patients with interstitial lung disease associated with RA often have increased numbers of lymphocytes in the alveolar structures, it seemed possible that rheumatoid lung disease could also be associated with an imbalance of T-lymphocyte subpopulations. To test this hypothesis, patients with chronic interstitial lung disease and RA were evaluated by lung biopsy, gallium-67 scanning and bronchoalveolar lavage to assess the activity of the lung disorder and the T-lymphocyte subpopulations were identified with the OKT4, OKT8 and Tec T-5.9 monoclonal antibodies. The Tec T-5.9 is a recently described monoclonal antibody which recognizes a small T-cell fraction of the OKT4 positive T-lymphocytes, responsible for many helper T-cell functions, including the response to allogenic antigens and help in immunoglobulin production by B-cells. Histologic evaluation of the biopsies demonstrated active lung inflammation in all patients and gallium-67 scans showed an increased lung uptake in five of the six patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)