Novel method and parameters for testing and characterization of foam stability.

The paper presents novel parameters which can be used for a swift characterization of all kinds of liquid foams. The procedure of the automated method developed consists of introducing a predefined volume of gas into the test solution contained in a cylindrical glass column at constant flow rate. The levels of the foam and of the solution are recorded simultaneously in dependence on time using a photosensor system. Two novel parameters, called time of deviation and time of transition, have been derived on the basis of simultaneous measurements of the changes in the foam volume (DeltaV(F)) and the corresponding volume of the drained solution (DeltaV(S)). These parameters enable one to distinguish three different stages of the foam decay, and on their basis the foam stability can be predicted, irrespective of whether constituting an unstable (wet) or a (meta)stable (dry) foam system. The validity of the method elaborated is demonstrated by applying various unstable and stable foam systems, including biological surfactants such as sugar and lung surfactants.

[Breath condensate as a method of noninvasive assessment of inflammation mediators from the lower airways]. / Das Atemkondensat als Methode zur nicht-invasiven Erfassung von Entzündungsmediatoren aus den unteren Atemwegen.

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.

[Relation between 67-gallium scintigraphy and bronchoalveolar lavage--differential cell count and superoxide anion liberation--in patients with systemic scleroderma and systemic lupus erythematosus]. / Beziehungen zwischen 67-Gallium-Szintigraphie und bronchoalveolärer Lavage--Differentialzellbild und Superoxid-Anion-Freisetzung--bei Patienten mit systemischer Sklerodermie und systemischem Lupus erythematodes.

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.

[Bronchoalveolar lavage in patients with systemic scleroderma and systemic lupus erythematosus: characterization of cell activity by cytofluorometry, chemiluminescence and differential cell count]. / Bronchoalveoläre Lavage (BAL) bei Patienten mit systemischer Sklerodermie und systemischem Lupus erythematodes: Charakterisierung der Zellaktivität durch Zytofluorometrie, Chemilumineszenz und Differentialzellbild.

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.

[Clinical pharmacology in optimization of therapy of lung diseases]. / Klinische Pharmakologie bei der Therapieoptimierung von Lungenkrankheiten.

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.

[Chemiluminescence measurements of bronchoalveolar lavage cells in patients with collagenosis]. / Chemilumineszenz-Messungen an Zellen der bronchoalveolären Lavage bei Kollagenose-Patienten.

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.

[Short scientific report. Vitamin C lessens superoxide anion(O2)-induced bronchial constriction]. / Kurze wissenschaftliche Mitteilung. Vitamin C vermindert die superoxid-anion(O2)-induzierte bronchokonstriktion.

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.

Failure of ambroxol to influence the allergen induced bronchial constriction in sensitized guinea pigs.

The action of ambroxol was tested in an in vivo guinea pig asthma model. Ambroxol, a compound with antiallergic properties effects the mediator releasing cells in vitro and surfactant secretion from alveolar type II cells. This paper deals with the action of ambroxol in an in vivo asthma model in guinea pigs. Ovalbumin sensitized guinea pigs were artificially ventilated by negative chest wall pressure, using a tank respirator. Breathing parameters were measured pneumotachographically. The experimental animals were treated with 50 mg/kg ambroxol i.p. for 5 days; control animals received saline only. The results indicate that pretreatment with ambroxol had no significant effect on the allergic bronchial constriction, while in vitro ambroxol effects on mediator releasing cells and surfactant production point to antiallergic properties. An explanation of the failure of allergenic preventing effects of ambroxol in vivo may be its insufficient concentration in the tissue.

[Tracheal instillation of arachidonic acid as an asthma model in guinea pigs--preliminary results of the effect of inhibitors of arachidonic acid metabolism]. / Tracheale Instillation von Arachidonsäure als Asthmamodell am Meerschweinchen--erste Ergebnisse zum Einfluss von Hemmstoffen des Arachidonsäuremetabolismus.

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.

[Chemiluminescent measurements of alveolar macrophages in sarcoidosis patients]. / Chemilumineszenz-Messungen an Alveolarmakrophagen bei Sarkoidose-Patienten.

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.

[Effect of antioxidants on the production of reactive oxygen metabolites by stimulated alveolar macrophages]. / Einfluss von Antioxidanzien auf die Erzeugung von reaktiven Sauerstoffmetaboliten durch stimulierte Alveolarmakrophagen.

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.

[The effect of ambroxol and bromhexine on the "respiratory burst" of alveolar macrophages]. / Einfluss von Ambroxol und Bromhexin auf den "Respiratory Burst" von Alveolarmakrophagen.

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.

[Liposomes from hydrogenated egg yolk lecithin]. / Untersuchungen an Liposomen aus hydriertem Eilecithin.

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.

[Clinico-experimental studies of therapy optimization in kidney tuberculosis]. / Klinisch-experimentelle Untersuchungen zur Therapieoptimierung der Nierentuberkulose.

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.

[The pharmacokinetics of rifampicin in the intermittent treatment of patients with pulmonary tuberculosis. 1. Excretion of rifampicin in the urine]. / Zur Pharmakokinetik des Rifampicins (RMP) bei intermittierender Behandlung von Patienten mit Lungentuberkulose. 1. Mitteilung: Zur Ausscheidung von RMP im Harn.

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.

[Modulation of alveolar macrophage activity by ambroxol, bromhexine and exogenous arachidonic acid]. / Modulation der Alveolarmakrophagenaktivität durch Ambroxol, Bromhexin und exogene Arachidonsäure.

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.

[Bronchoalveolar lavage]. / Bronchoalveolärre Lavage.

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.