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The detection of mediators from the lower airways still depends on invasive or provoking sampling techniques like bronchoalveolar lavage (BAL) or induced sputum, respectively. Both methods affect the specimen itself. In contrast, the breathing condensate opens the possibility to get native specimens from lower airways during breathing at rest. The breathing condensate was obtained by freezing of exhaled air. The equipment was developed in the FILT Res. Soc. Ltd.. The method is applied for a patent. Leukotriene B4 and Leukotriene C4D4E4F4 were measured in the exhalation of asthmatics, patients with different airway disorders and healthy volunteers. In an additional study the condensate was obtained before and after of a non-specific bronchial challenge test. In asthmatics a close correlation between leukotriene concentration of the condensate and the degree of asthmatic disease according to "International Consensus Report" was found, but no correlation to lung function tests. Within a bronchial challenge test applying histamine the release of leukotrienes was shown to be more sensitive to the challenge test than a lung function test. The results of the study indicate new diagnostic possibilities in lung diseases using the detection of non volatile substances in the exhaled air.

The aim of the study was to determine the pulmonary 67-gallium uptake, bronchoalveolar lavage (BAL) cell differentiation and the activity of BAL cells, measured as release of superoxide anion (O2-), and to investigate the results whether there are relations. In 11 nonsmoking systemic scleroderma (SS) patients and 11 systemic lupus erythematosus (SLE) patients with lung involvement double-sided BAL were performed, mainly in regions with increased 67-gallium uptake. Release of O2- was measured by INT-assey. BAL cell differentiation was in SS and SLE pathological in 68.2% without side-difference. In contrast to SS, O2(-)-release in SLE depends on BAL cell differentiation and is most increased in normal BAL cell differentiation. There is no correlation between 67-gallium uptake and both BAL cell differentiation and O2(-)-release. The results suggest, that in contrast to SS, BAL cells in SLE with pathological differentiation are less activated than BAL cells with normal differentiation probable due to autoimmunological factors. Pulmonary 67-gallium scan and BAL seem to be independent from each other.

The purpose of the study was to determine the role of lymphocyte subsets (Ly) and reactive oxygen metabolites RSM, concerning the activity of BAL cells, in the pathogenesis of lung involvement in 12 patients with systemic sclerosis (SS) and 4 with systemic lupus erythematodes (SLE) in comparison with 10 control subjects. The cellular activity was measured by means of cytofluorometry (CFM) and chemiluminescence (CL). In SS/SLEY CD3+, CD4+, CD4/CD8-ratio, CD25 + T-Ly and luminol-dependent CL are increased (p less than 0.05). Correlations exist between CD3+, CD4+, CD8+ and CD25 + T-Ly and both luminol-dependent CL and neutrophils (p less than 0.01). The results suggest, that increased secretion of RSM by BAL-cells may be caused by local release of lymphokines by these activated T-Ly. Therefore CFM and CL seem to be useful in addition to BAL cell differentiation in characterizing the BAL cell activity in the diagnostic of lung involvement in SS and SLE.

The optimization of the therapy of lung tuberculosis and asthma bronchiale was supported since 1955 by clinical-pharmacological investigations. The prerequisites therefore--using highly specific methods of distribution and quantification in biological material till to the synthesis of 3H-INH and 3H-RMP were introduced step by step. The investigations--in most cases estimations of the nonbiotransformated part of antituberculotic drugs and theophylline had following purposes: security of the necessary dose especially in the case of INH (hereditary INH-polymorphismus), proof of a sufficient permeation of INH and RMP in the tuberculous kidney, control of the usefulness or uselessness of the INH-depot-preparations, relations between the concentration in the serum and dose respectively of the appearance of side effects, estimation of bioavailability and pharmacokinetic parameters during the development of an useful retard-preparation of theophylline.

The purpose of the study was to determine the role of reactive oxygen metabolites in the pathogenesis of interstitial lung involvement in 13 patients with collagen vascular diseases (CVD) in comparison with 10 control subjects. The cellular activity of bronchoalveolar lavage (BAL) cells was measured by means of chemiluminescence (CL), spontaneously and after challenge of the cells with opsonized zymosan (simultaneously luminol- and lucigenin-dependent). The findings show an increase of the spontaneous and stimulated CL of BAL cells in CVD, more pronounced in luminol-dependent CL. The luminol-dependent CL correlates with neutrophils in BAL cell differentiation. The results suggest that reactive oxygen metabolites take part in interstitial lung involvement in patients with CVD. Therefore the measurement CL of BAL cells is useful in addition to BAL cell differentiation in diagnostic of interstitial lung involvement in CVD.

A short review of the different methods for light microscopic demonstration of phospholipids in the lung tissue is given. As shown in own experiments, the phosphomolybdic-acid-stannous-chloride reaction (Landing et al., 1952) appears as a successful method for rapid demonstration of phospholipids.

The effect of ambroxol and bromhexine on the yeast cell wall- and arachidonic acid (AA)-induced luminol-respectively lucigenin-dependent chemiluminescence (CL) of alveolar macrophages (AM) of patients with lung diseases has been investigated. Both drugs cause a suppression of the induced CL. These results suggest that ambroxol and bromhexine reduce the generation of reactive oxygen metabolites (ROM) by AM. The mechanism of action is thought to involve the activation of the acyl-CoA: lysophosphatide acyltransferase. The increase of this enzyme activity lowers probably the intracellular concentration of free AA and consequently also the production of ROM. The investigations show a new possibility for the influence of biosynthesis of ROM and likely of eicosanoids, which play an important role as pathogenetic mediators in different lung diseases.

In the lungs of LEWE-Mini-Pigs with aspiration pneumonitis, which was produced by intratracheal application of 0,2 n hydrochloric acid, the following parameters were determined post-mortally: Total phospholipid-, water- and cholesterol content and sphingomyelin-, lecithin-, phosphatidylethanolamine- and phosphatidylserine concentration. Furthermore thin-layer- and gelchromatographic investigations were performed. The water- and the cholesterol content are increased (about 4 respectively 40 percent). The total phospholipid- and the lecithin content are decreased (about 10 respectively 30 percent). The lysolecithin concentration is very low in the lungs. By therapy with bromhexine metabolite VII the water- and cholesterol content are reduced, the total phospholipid- and lecithin content are increased in comparison to the lungs without therapy. In this case the total phospholipid- and lecithin content are raised in the liver simultaneously. The biochemical changes are caused probably by a disorder of the surfactant system of the lung (disturbance of phospholipid-protein-interaction) and impairment of the alveolar epithelial cells typ II (decreased lecithin biosynthesis) in consequence of the action of the hydrochloric acid.

The use of antituberculotic short-term chemotherapeutic methods did not yet make its way on a larger scale in the treatment of the extrapulmonary tuberculosis on account of supposed peculiarities of the terrain. Therefore, the present clinical and experimental study had the aim to investigate the distribution of INH and RMP in the kidney and the radiometrical determination of their concentration directly in the tuberculous focus of the kidney. For this purpose the tritium labelling of the two basis antituberculotics mentioned was carried out. Apart from the description of the applied working and measuring technique, questions of the distribution of medicaments are discussed. The results made evident that also in kidneys widely destroyed by tuberculosis both INH after an intravenous application of 300 mg and RMP after oral application of 600 mg even in large tuberculous caverns achieve antimycobacterially effective concentrations. Indeed, there are considerable differences, however, the values were always far above the minimum inhibition concentration. Thus there are no terrain-caused peculiarities for the tuberculous kidney and also no restrictions as to the use of an optimized antituberculotic chemotherapy. The same is probably also applied to all other forms of the extrapulmonary tuberculosis. The newly developed method distinguishes itself by a high measuring exactness and could analogously be used in questions of the chemotherapy of malignant tumours.

An in-vivo asthma model in guinea pig by tracheal instillation of sodium-arachidonate in artificially ventilated animals was introduced. The introduced model seems to be sufficient for testing inhibitors of arachidonate metabolism for antiasthmatic activity.

The incidence of interstitial lung diseases is increased during the last years. A possibility for improvement the diagnosis of these lung diseases is the bronchoalveolar lavage (BAL). In a critical review the performance of the BAL, same properties of the isolated macrophages and the determination of biochemical parameters in lavage fluid are described. In this context especially problems of diagnosis of sarcoidosis are discussed. There are new fields of application of BAL (diagnosis of occupational lung diseases, control of therapy). In order to improve the comparability of different results a standardization of BAL is necessary.

Electron microscopical, autoradiographical and histochemical investigations were carried out in experimental lipid pneumonia, 6 weeks after exposure to mineral oil. In the lungs developed granulomatous changes with fibroblasts, some macrophages and leucocytes. With the aid of electron microscopy an increased number of fibroblasts with predominantly extracellular localized collagen fibers were visible in the granulomatous foci. Autoradiograms with 3H-Thymidine show an six-fold increase of number of radioactive labelled nuclei of fibroblasts in the granulomatous areas. This two methods--electron microscopy and autoradiography--appear sufficient for early detection of changes in experimental lung fibrosis.

Today there are still difficulties by differentiating of chylous pleural effusions. It is reported about two forms of chylothorax which are different in their etiology. The chyle were examined with regard to the fats. It can be shown that the thin-layer chromatography of lipids makes possible a rapid diagnostics of chylous pleural effusions.

In a small number of patients, lung emphysema can be attributed to a remarkable deficiency of alpha1-antitrypsin. Concentrations reduced about 50% of the normal value represent a predisposing factor. In most cases of newborns with respiratory-distress-syndrome the concentration of alpha1-antitrypsin is decreased. Its determination can be used for the early diagnosis of the respiratory-distress-syndrome.

The present paper describes a simple method for the extracorporeal hypothermic perfusion of isolated lungs during the experimental lung transplantation in the dog. Two different solutions were used: sodium chloride-solution and Dextran-electrolyte-solution. The temperature of the perfused lung falls to 14 degrees C. The water-content is significantly increased by using the sodium chloride-solution, it is slightly increased after perfusion with Dextran-electrolyte solution. The total phospholipid-content is decreased in lungs perfused with sodium chloride-solution, it is significantly increased in lungs perfused with Dextran-electrolyte-solution.

The investigations of the last 10 years have shown that beside the respiratory function the biochemical processes of the lungs are of basic importance. The normal biochemical processes are the prerequisite to a normal respiratory function. Today the problems of air pollutants are topical. Therefore a review of the new literature about the influence of air pollutants on biochemical processes of the lungs is given. The following substances are included: gaseous air pollutants (ozone, NO2, SO2, phosgene) and aerosols as well as dust (cadmium, paraquat, carcinogens, tobacco smoke). Furthermore the biochemical changes of the lungs by high and low oxygen concentrations are described. Our knowledge concerning the simultaneous influence of several pollutants, the possibilities for an early biochemical detection of damages caused by air pollutants, and their therapeutical influence are still limited.

After injection of an anti-lung -serum a respiratory distress syndrome could be produced in spontaneously-breathing guinea pigs. Reduced compliance, increased resistance and work of breathing was found. Morphological investigations showed intraalveolar and interstitial bleedings and a lung edema. Biochemically a decreased total phospholipid content could be found. Surface tension characteristics, examined with the Langmuir balance, were deteriorated. A complete restitution of surface tension parameters and total phospholipid content was obtained by administration of bromhexin metabolit Na 872.

The observations and the results after allogenic lung transplantation in 24 receivers were reported. The animals were not treated immuno-suppressively. They survived 6.2 days on an average and died in consequence of the rejection. The transplant is progressively threatened of bacterial infections after the beginning of the rejection even in case of an operation under sterile conditions. The investigations confirmed a narrow correlation between the leucocyte count and the course of the rejection. However, the condition of the transplant can be estimated approximately certainly by means of complex clinical methods of examination.

In order to characterize the pulmonary maturity during ontogenetic development the following parameters were determined in the lungs of 30 fetuses respectively newborns with a weight between 15 and 4450 g: Water content (WC), total phospholipid content (TPC), lecithin concentration (LC), sphingomyelin concentration (SPC) and surface activity (SA) of the extracts. The water content decreases with increasing gestation age. The total phospholipid content and the lecithin concentration increase during the ontogenetic development. The sphingomyelin concentration remains approximately constant during lung development. No significant correlation exists between phospholipid content and surface activity. A relatively high TPC and a high SA was found in a 43 g-fetus (about 14th week of gestation). This result suggests, that the surfactant-system of the lung is produced earlier than supposed till now. Lungs of infants who developed respiratory distress syndrome (RDS) have a low concentration of TPC. The lecithin/sphingomyelin-ratio rises as gestation progresses. Lungs of RDS-children have - similarly in amniotic fluid - a low lecithin/sphingomyelin-ratio.

In the last 30 years the production and consumption of cigarettes are increasing permanently. Till now more than 2200 noxious substances have been detected in the smoke of cigarettes. The origin and the synthesis of selected groups of these compounds and their distribution on main- and on sidestream smoke are described, furthermore the possibilities for estimation and control of nicotine abuse are reviewed. The incorporation of noxious substances of tobacco smoke result in a damage of clearance mechanisms of the lung and a change of loading by drugs and other metabolisable noxious substances, because the biotransformation processes are influenced by tobacco smoke. In this connection the importance of aryl-hydrocarbon-hydroxylase is discussed.

An in vivo model of acute lung damage provoked by free oxygen radicals in guinea pigs was introduced. Bronchial and pulmonary response was induced by tracheal instillation of Xanthine-Oxidase (XO)-Xanthine solution. The response was measured as a decrease of tidal volume during unchanged artificially ventilation. It was found that ascorbic acid pretreatment was effective to diminish the XO-induced reaction.

With a rifampicin (RMP) range of 600 to 1800 mg, 12.5% of the administered dose are on an average secreted in urine. In spite of this minimal portion the course of pharmacokinetic processes can distinctly be learned from its alterations. Analyses in 84 patients revealed that the age will influence the induction and the sex-specific differences of the pharmacokinetics. Compared to male subjects, an increased RMP secretion in urine can be recorded in young female subjects, whereas in older male ones an induction-reduced RMP elimination in urine becomes more obviously. Considering these multiform processes, the determination of the bioavailability of RMP preparations by means of the RMP secretion in urine is taken to be manipulatable and uncertainly. More evident results can be gained by the determination of the RMP concentration in serum or by the calculation of the AUC.

Egg yolk lecithin is a lipid, frequently been used for the liposome preparation. Such liposomes, however, are sensitive to oxidation and relatively permeable to encapsulated substances. The catalytic hydrogenation of egg yolk lecithin is one possibility to modify the properties mentioned. The authors deal with preparation and characterization of hydrogenated egg yolk lecithin. Liposomes from native and hydrogenated egg yolk lecithin--also in combination with cholesterol--are compared. Liposomes with hydrogenated egg yolk lecithin as phospholipid component exhibit a significantly increased encapsulation capacity and an essentially improved stability. The permeation of electrolytes, carboxyfluorescein and of the cytostatic drug daunorubicin is studied.

The increased generation of reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, X OH, OX-) by alveolar macrophages (AM) and neutrophils has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. With regard to a possible therapeutic application in this context the effect of bromhexine and ambroxol on the activity of AM of of guinea-pigs and of patients with lung diseases was investigated. The activity of AM, which were isolated by bronchoalveolar lavage, was determined by means of chemiluminescence (CL)-measuring. Ambroxol and bromhexine cause a depression of the spontaneous as well as of the induced CL [yeast cell walls, yeast glucan, exogenous arachidonic acid (AA)] of AM. AM from guinea-pigs and in some cases also from patients show primarily an increase of the CL-signal under the influence of bromhexine. These results suggest that ambroxol and bromhexine reduce the production of ROM by AM. The mechanism is possibly due to the activation of acyl-CoA-lysophosphatide acyltransferase. The increase of this enzyme activity lowers the intracellular concentration of the free AA, whereby the generation of ROM is diminished too. The investigations exhibit a new possibility of influence of respiratory burst and thus indirectly of AA-liberation from phospholipids. The probable reduction of AA-liberation by these drugs could also be of importance for other lung cells especially concerning the biosynthesis of eicosanoids (AA-metabolites), which play an important part as pathogenetic mediators in different lung diseases.

The phagocytic activity of alveolar macrophages (AM) in a group of patients with stage I, stage II and stage III pulmonary sarcoidosis (gradation according to Wurm) has been investigated. Additionally a classification in different forms of the course of sarcoidosis was made (acute = Loefgren's syndrome, latent = primary-chronic, and relapses). Patients with other lung diseases and healthy subjects were recruited as control group. The phagocytic activity (stimulation with opsonized yeast cell wall particles) of AM, which were isolated by bronchoalveolar lavage, was determined by means of chemiluminescence (CL)-measuring using lucigenin and luminol, respectively, as amplifiers. The investigations showed that the lucigenin-dependent yeast cell wall-induced CL of AM in patients with sarcoidosis is significantly increased in comparison to the control group. No significant changes of the luminol-dependent CL of AM from sarcoidosis patients could be detected. The lucigenin-dependent CL-response of AM is obviously an indicator of the intensity of the alveolitis and thus of the activity of the pathological process in sarcoidosis. The results suggest that in pulmonary sarcoidosis there is a hyperreactive AM/lymphocytes-system.

Morphological investigations (light microscopy, semithin sections, histochemistry) on autografted lungs showed two changes with mifferent regional distributions. In the upper lobes were found focal areas of slight fibrosis, in the upper and lower lobes degenerative changes especially of the small bronchi and bronchioles with a focal loss of activity of alkaline phosphatase, nonspecific esterase and some dehydrogenase. Possible reasons for these morphological changes are discussed in connection with functional and biochemical results.

Reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, .OH, OX-) which are produced by stimulated alveolar macrophages (AM), neutrophils and eosinophils, play an important role in the pathogenesis of many acute and chronic lung diseases. With regard to a therapeutic application the influence of the antioxidants ascorbic acid (Vitamin C) and alpha-tocopheryl acetate (Vitamin E acetate) on the production of ROM by AM was investigated. The AM were isolated by bronchoalveolar lavage from patients with different lung disorders. The ROM were determined by means of chemiluminescence-measuring. alpha-Tocopheryl acetate solved in peanut oil causes a little increase of the yeast cell wall-induced chemiluminescence. Pure alpha-Tocopheryl acetate has no effect on the chemiluminescence. In contrast to alpha-Tocopheryl acetate the addition Vitamin C to the stimulated AM results in a strong diminution of the chemiluminescence signal. This result suggests that Vitamin C reduces the generation of ROM by AM. Therefore Vitamin C could be a suitable scavenger of radicals and oxidants in different lung diseases.

A ratio-test (Isoniazid: acetyl-isoniazid) is used for phenotyping the Isoniazid-inactivation. The border-line between both the phenotypes is determinated. The influence of age and weight of the patients is studied. Usefully results are obtained after application per os of an uniform dosage and a sampling period for urine of 4 hours. Increasing the dosage to 900 mg the portion of isoniazid arises mmore than proportionally, more distinct in rapid than in slow inactivators. Therefore the differences between the two phentoypes are diminished. The clinical importance of these results is discussed.