Absorption and metabolism of intratracheally instilled cortisol and beclomethasone dipropionate in the isolated perfused rat lungs

The fate of [4-14C]-cortisol and [16,16 alpha-3H]-beclomethasone dipropionate following intratracheal application of the substrates into isolated perfused rat lungs was studied. Both substrates were transferred to the perfusion medium, cortisol at a much higher rate than beclomethasone dipropionate. The proportion of different metabolites of the total radioactivity was larger with beclomethasone dipropionate in both the perfusion medium and the lung tissue. The lungs are considered to have a catabolic role in cortisol metabolism.     

Vascular segmental permeabilities at high peak inflation pressure in isolated rat lungs

The response of segmental filtration coefficients (Kf) to high peak inflation pressure (PIP) injury was determined in isolated perfused rat lungs. Total (K f,t ), arterial (K f,a ), and venous (K f,v ) filtration coefficients were measured under baseline conditions and after ventilation with 40-45 cmH(2)O PIP. K f,a and K f,v were measured under zone I conditions by increasing airway pressure to 25-27 cmH(2)O. The microvascular segment K f (K f,mv ) was then calculated by: K f,mv = K f,t - K f,a - K f,v. The baseline K f,t was 0.090 +/- 0.022 ml. min(-1). cm H2O(-1). 100 g(-1) and segmentally distributed 18% arterial, 41% venous, and 41% microvascular. After high PIP injury, K f,t increased by 680%, whereas K f,a, K f,v, and K f,mv increased by 398, 589, and 975%, respectively. Pretreatment with 50 microM gadolinium chloride prevented the high PIP-induced increase in K f in all vascular segments. These data imply a lower hydraulic conductance for microvascular endothelium due to its large surface area and a gadolinium-sensitive high-PIP injury, produced in both alveolar and extra-alveolar vessel segments.     

Factors determining the degree of anaerobiosis of Bifidobacterium strains

Summary The degree of sensitivity of twelve Bifidobacterium (Lactobacillus bifidus) strains to O₂ was determined by measuring the size of the inhibition zones obtained when the bacteria were grown in deep agar cultures under air, and by measuring growth in aerated cultures. The size of the inhibition zones varied from 1 to 23 mm. Growth in aerated cultures differed markedly for the strains investigated. No strain grew on agar plates under aerobic conditions.The small inhibition zone of three Bifidobacterium strains might be explained by the presence of a weak catalase activity, which removes traces of H₂O₂ possibly formed. It is also possible that the NADH oxidase of these strains does not form H₂O₂ at all. Most probably, the lack of growth on an agar medium results from the fact that these strains only grow below a certain oxidation-reduction potential.One strain, which was rather insensitive to O₂, formed a small amount of H₂O₂ from NADH oxidation. The absence of H₂O₂ in aerated liquid cultures and cell suspensions of this strain, which lacked catalase and NAD peroxidase activity, must be explained by removal of the traces of H₂O₂ formed, by an unknown peroxidase system or by a chemical reaction with pyruvate formed during glucose fermentation.For two strains, which were moderately sensitive to O₂, accumulation of H₂O₂ seems to be the principal reason for anaerobiosis. H₂O₂ turned out to inactivate specifically fructose-6-phosphate phosphoketolase, a key enzyme of the fermentation pathway of bifidobacteria.In the culture medium of two strains, which were extremely sensitive to O₂, no H₂O₂ could be detected after aeration. During anaerobic growth of these strains, the oxidation-reduction potential of the culture decreased so much that neutral red was decolourized. Cell suspensions of these strains only fermented glucose when cysteine was added. It was concluded that these strains required a low oxidation-reduction potential for growth and fermentation.     

Ultrastructural changes in the lungs of neonatal rats intratracheally inoculated with meconium

Meconium aspiration syndrome has been for many years an important cause of neonatal respiratory distress in newborn babies and sporadically reported in animals. This investigation was designed to study the ultrastructural and morphometric changes in the lungs of neonatal rats following the intratracheal inoculation of meconium. Seven-day-old Fischer-344 rats (n = 24) were randomly allocated in two groups. One group was intratracheally inoculated with saline solution and the second group received homologous meconium. Neonates were euthanatized at 1, 3 and 7 postinoculation days (PID) and lungs were examined by light and electron microscopy. Saline solution did not induce any ultrastructural changes in the lung. In contrast, meconium induced deciliation, recruitment of neutrophils and pulmonary alveolar macrophages to the bronchoalveolar space, intravascular sequestration of neutrophils and aggregation of platelets at PID 1 and 3. Other ultrastructural changes at PID 1 and 3 included interstitial edema and escape of red cells and fibrin into the alveolar space and interstitium. Interstitial edema and sequestration of neutrophils were responsible for the significant increase in thickness of alveolar septa. At PID 7 there was hyperplasia and enlargement of type II pneumocytes as well as interstitial proliferation of mesenchymal cells with intra-alveolar fibrosis. It was concluded that intratracheal inoculation of meconium in neonatal rats induces acute ultrastructural changes followed by a reparative response.     

Factors determining the degree of endometrial exfoliation and their diagnostic implications in endometrial adenocarcinoma

Since the degree of endometrial exfoliation largely determines the ability of cytology to diagnose endometrial adenocarcinomas by the study of cervicovaginal smears, five features of their subsequent histologically diagnosed endometrial adenocarcinomas were studied in 28 patients whose smears contained endometrial cells. The surface area occupied by abnormal endometrium was found to be an important determinant in the degree of endometrial exfoliation. The tumor grade, endocervical involvement, pattern of growth and squamous-cell component were all factors that influenced cellular shedding. The extent of myometrial involvement did not affect the likelihood that an endometrial adenocarcinoma would be diagnosed cytologically prior to histologic examination.     

Effect of lung inflation on fluid flux in zone 1 lungs

Because of conflicting data in the literature, we studied the effect of positive-pressure inflation on transvascular fluid filtration in zone 1 lungs. Lungs from New Zealand White rabbits (n = 10) were excised, perfused with saline and autologous whole blood (1:1), ventilated, and continuously weighed. Pulmonary arterial and venous pressures (Pvas) were referenced to the most dependent part of the lung. A change in vascular volume (delta Vvas) and a fluid filtration rate (FFR) were calculated from the change in lung weight that occurred from 0 to 30 s and from 3 to 5 and 5 to 10 min, respectively, after changing alveolar pressure (PA). FFR's and delta Vvas's were measured with Pvas equal to 2 or 10 cmH2O and PA changing from 15 to 30 cmH2O when the lungs were normal and after they were made edematous. When Pvas = 2 cmH2O, increasing PA increased the Vvas and the FFR in both normal and edematous lungs. However, when Pvas = 10 cmH2O, increasing PA only slightly changed the Vvas and reduced the FFR in the normal lungs, and decreased Vvas and markedly decreased the FFR in the presence of edema. Inflating zone 1 lungs by positive pressure has an effect on transvascular fluid flux that depends on the Pvas. The results suggest that the sites of leakage in zone 1 also vary depending on Pvas and PA.     

Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally

Hybertson, Brooks M., Stuart L. Bursten, Jonathan A. Leff,Young M. Lee, Eric K. Jepson, Chris R. Dewitt, John Zagorski, Hyun G. Cho, and John E. Repine. Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1intratracheally. J. Appl. Physiol.82(1): 226-232, 1997.Interleukin-1 (IL-1) is increased in lunglavages from patients with the acute respiratory distress syndrome, andadministering IL-1 intratracheally causes neutrophil accumulation and aneutrophil-dependent oxidative leak in lungs of rats. In the presentstudy, we found that rats pretreated intraperitoneally with lisofylline[(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (LSF)], an inhibitor of lysophosphatidic acid acyl transferase, which reduces the production of unsaturated phosphatidic acid species,did not develop the lung leak or the related ultrastructural abnormalities that occur after intratracheal administration of IL-1.However, rats pretreated with LSF and then given IL-1 intratracheally did develop the same elevations of lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels and the same increased numbersof lung lavage neutrophils as rats given IL-1 intratracheally. Lungs ofrats given IL-1 intratracheally also had increased unsaturated phosphatidic acid and free acyl (linoleate, linolenate) concentrations compared with untreated rats, and these lipid responses were prevented by pretreatment with LSF. Our results reveal that LSF decreases lungleak and lung lipid alterations without decreasing neutrophil accumulation or lung lavage CINC increases in rats given IL-1 intratracheally.

     

Factors influencing the growth of alveolar type II epithelial cells isolated from rat lungs

Primary cultures of isolated alveolar type II cells have been established. Under appropriate conditions, these epithelial cells can be subcultured at least nine times. Using standard assay procedures, effects of growth factors or inhibitors can be studied. The alveolar type II cells show a marked response to both serum and growth factors in tissue culture. Either epidermal growth factor (EGF) or human urine gives an increase in thymidine incorporation (2-fold and 10-fold, respectively). The growth factor(s) in urine appears to be different from urogastrone (human EGF). The response to urine is several-fold greater than the response to a saturating concentration of mouse EGF alone. Mouse EGF added to urine does not increase the activity of urine. The period during which the alveolar type II cells respond to the growth factor(s) in urine is limited to early passages of the cells. Alveolar type II epithelial cells produce growth inhibitors in culture. Inhibitors are produced in the growth medium in either the presence or absence of serum. The concentrated inhibitor, although very unstable, gives up to a 50% inhibition of thymidine incorporation when assayed on sparse or crowded alveolar type II cells.     

A study of inflation of the lungs of the newborn; a preliminary report

There seems to be no reasonable doubt that the lungs in a newborn expand progressively during the first few days of life. Some degree of atelectasis seems to be perfectly normal. This is indicated by a number of roentgenographic studies (including those here reported); by the reported findings of pathologists; by the fact that in experimental animals the lungs inflated very unevenly; and by the fact that aeration of only a portion of the lung is needed for complete oxygenation of the blood. The relation of atelectasis to neonatal death is not entirely clear and is probably not always the same. The infant may die from other causes before the lungs are fully expanded. Atelectasis may develop secondarily to other debilitating conditions. The frequent coincidence of prematurity and extensive atelectasis is impressive. It may be that the lungs are so incompletely formed that they cannot expand. On the other hand, atelectasis and massive collapse in the adult is a serious condition and there seems to be no good reason to suppose that this cannot also occur in infants and be serious per se. The air pressures found necessary to expand the lungs in rabbit fetuses were found to be about ten times what adult humans use in quiet respiration and were of about the same magnitude as the pressures found necessary to expand the lungs of stillborn humans. An attempt to produce atelectasis in newborn rabbits by chilling was most inconclusive. Atelectasis did develop in three of 15 animals used in the experiment, but the relation to chilling was not at all clear.