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1.
We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical
responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance
(Rrs) and inspiratory static respiratory system compliance (Crs) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. Rrs responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC150) and intravenous spasmogen dose (PD150) causing an increase in Rrs to 150% of baseline. Crs responsiveness was calculated similarly for a decrease in Crs to 85% of baseline (PC85 for inhaled and PD85 for intravenous spasmogen). Baseline Rrs and Crs were similar in all groups. Rrs responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains.
In contrast, Crs responses were variable and had a greater mean PC85 for inhaled serotonin than carbachol in both strains and a greater fall in mean Crs at PC150 for carbachol in Balb/C mice; no interstrain and interdrug differences in PD85 were noted for intravenous spasmogens. Intravenous atropine attenuated the Rrs response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine
attenuated Crs responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of
administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil.
Accepted for publication: 24 June 1999 相似文献
2.
The dose dependence and time course of smoke inhalation injury were determined in a rabbit model. Animals were insufflated
with 18–90 breaths of cotton smoke or room air (control) at a rate of 18 breaths/min and tidal volume of 12 ml/kg. Smoke-exposed
animals exhibited dose-related histologic effects with progressive deterioration of respiratory function during the postexposure
period of observation (96 h). The smoke-exposed rabbits had reproducible injuries to both airway mucosa and lung parenchyma,
manifested by disruption and sloughing of airway and alveolar epithelia, and exudation of protein-rich fluid and leukocytes
into the airway and alveolar spaces. Significant effects were evident by 24 h postexposure. Smoke inhalation also affected
the respiratory burst of alveolar macrophages. Generation of superoxide anions by alveolar macrophages at 48 h postexposure
was increased significantly after smoke inhalation (54 breaths). The present rabbit model should be useful for studying the
interactions between pulmonary epithelial cells and leukocytes after smoke inhalation and for determining the role that abnormal
functioning of alveolar macrophages plays in the development of smoke inhalation injury.
Accepted for publication: 8 October 1998 相似文献
3.
Nitric oxide (NO) is an important mediator in the regulation of bronchial muscle tone and airway responsiveness. We investigated
the influence of exogenous NO on airway responsiveness to acetylcholine aerosols (ACH) in normal and in hyperresponsive rabbits.
White New Zealand rabbits were anesthetized, intubated, and breathed room air spontaneously. Responses of respiratory parameters
in ACH challenge tests were measured. In group A the influence of NO on ACH infusion-induced airway constriction was measured.
Airway responses to aerosols from 0.25 to 8.0% ACH solutions in saline were measured with 150 and 300 ppm NO inhalation (groups
B and C) and compared with the same animals' responses without NO. Moreover, we examined the influence of NO synthase inhibition
on airway responsiveness (group D) and the modulatory effect of NO in hyperresponsive animals (group E). 300 ppm NO inhalation
significantly decreased the bronchoconstrictor response to intravenously administered ACH (group A). However, the baseline
value of dynamic elastance (Edyn) was only marginally lower under the influence of 300 ppm NO. During inhalation of 150 or 300 ppm NO, responses to nebulized
2.0% and less ACH solutions remained nearly unaltered. Responses to aerosols of 4.0 and 8.0% diminished significantly (groups
B and C). Following 40 min of aerosolized N-nitro-l-arginine-methyl ester (l-NAME) solution (a NO synthase inhibitor, 1.2 mM) inhalation, the response of Edyn to ACH increased significantly in group D. In group E, animals inhaled 500 mg/m3 ammonium persulfate (APS), an oxidant with various industrial applications, after the first ACH challenge test (0.2, 1.0,
and 2.0% ACH). After 2 h of APS exposure, the ACH-induced broncho constriction was increased significantly in the challenge
test. After another 2 h of APS inhalation, the airway responsiveness to ACH was tested under the influence of 300 ppm NO.
NO significantly decreased the response to ACH to almost the same level as before APS exposure. The results indicate that
responses to high ACH concentrations as well as an APS-induced increase in ACH responsiveness were effectively reduced by
high concentrations of inhaled NO.
Accepted for publication: 11 February 1997 相似文献
4.
Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness
to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported
that the airways of such subjects maintained on chronic baclofen (γ-aminobutyric acid) therapy were not hyperreactive to inhaled
methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine
in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained
on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized
histamine until either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%)
and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders in the baclofen (PC20= 2.91 ± 2.3) and control (PC20= 2.18 ± 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on
cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due
to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.
Accepted for publication 21 January 1997 相似文献
5.
Inhaled endotoxin, lipopolysaccharide (LPS), has been shown to result in bronchial hyperresponsiveness (BHR) to endogenous
bronchoconstrictive mediators such as histamine. To determine the role of sensory neuropeptides released from bronchopulmonary
C-fibers in LPS-induced BHR, 24 guinea pigs were allocated randomly to the following four groups. Animals in Groups I and
IV were challenged with intratracheal instillation of 100 μl of saline vehicle, and those in Groups II and III with 1 mg of
LPS (Escherichia coli, 0111:B4) in 100 μl of saline. Groups III and IV also received a high dose capsaicin (HDC) treatment to deplete tachykinins
from C-fibers 1–2 weeks prior to the experiment. Animals were anesthetized and paralyzed, and total lung resistance (RL) and compliance (Cdyn) were measured continuously during the experiment. Dose responses of RL and Cdyn to histamine (0–8 μg/kg, intravenously) and capsaicin (0–1.6 μg/kg, intravenously), a specific C-fiber stimulant, were obtained
prior to and at 1, 2, and 3 h following LPS/saline vehicle challenge. At 2 h after LPS, ΔRL caused by histamine (8 μg/kg) was significantly higher in Group II (1.145%) than that in Group I (280%; p < 0.05); similarly, ΔRL caused by capsaicin (1.6 μg/kg) was also increased after LPS (Group I, 107%; Group II, 267%; p < 0.05). Although HDC treatment completely abolished the bronchomotor response to capsaicin in both Groups III and IV, it
enhanced the LPS-induced BHR to histamine (8 μg/kg; Group III, 1.834%; p < 0.05). In conclusion, these results suggest that the role of tachykinins in LPS-induced BHR may be dependent upon the type
and the route of administration of the bronchoactive substance studied.
Accepted for publication: 13 December 1996 相似文献
6.
E. Kreuzfelder G. Scheiber K. Quabeck U. W. Schaefer J. Bruch U. Costabel H. Grosse-Wilde 《Lung》1998,176(2):99-109
A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early
(<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early
or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein
permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after
BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease
than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage
(BAL) fluid albumin (alb) and serum β2-microglobulin (S-β2m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before
BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3
mg/dl) and S-β2m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications)
as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications)
1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population
at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes
(FEV1, 73% predicted, VC, 85% predicted).
Accepted for publication: 12 June 1997 相似文献
7.
Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to be important modulating factors for the
hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen radicals
modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs were divided into four groups: control, dimethylthiourea
(DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of LT receptor, whereas
A63162 is an inhibitor of lipoxygenase. Each group was further divided into three subgroups: baseline, hyperpnea, and recovery.
Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory compliance
(Crs), maximal expiratory flow at 50% total lung capacity (Vmax50), and forced expiratory volume in 0.1 s (FEV0.1) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, Vmax50, and FEV0.1, indicating HIB in the control group. Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (SP)
levels increased progressively during the experiment in all groups. However, both FPL 55712 and A63162, but not DMTU, significantly
decreased SP levels. Similarly, lung malondialdehyde (MDA) contents increased progressively during the experiment in the control
group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly attenuated the
increase in MDA during the recovery period. These results suggest that inhibition of LTs leads to suppression at SP levels
and HIB, whereas DMTU attenuates HIB by means of other mechanisms.
Accepted for publication: 25 April 2000 相似文献
8.
To ascertain whether chronic cigarette smoke exposure induces increased airway responsiveness, we performed methacholine
response tests in Sprague-Dawley rats by calculating pulmonary resistance after nebulization of saline followed by an increasing
concentration of methacholine. We also calculated the concentration of methacholine which doubled the baseline resistance
(R200). Tests were performed at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven cigarettes per
day, 5 days each week; control animals were exposed to room air. At the completion of the study, there were 13 rats in the
smoke-exposed group and 7 rats remaining in the control group. Airway morphology was assessed using a point counting technique.
We found that (1) chronic exposure to cigarette smoke did not alter either the baseline resistance or the R200; (2) the saline
baseline resistance decreased over time in the control animals; and (3) at the 12-month time point, smokers with increased
baseline airway resistance had greater amounts of airway smooth muscle compared with the smoke-exposed animals without increased
resistance. We conclude that in this animal model, long term exposure to cigarette smoke did not alter the response to methacholine
but did increase airway smooth muscle and baseline resistance in some but not all animals.
Accepted for publication: 4 December 1997 相似文献
9.
Airway Eosinophilic Inflammation and Bronchial Hyperresponsiveness after Allergen Inhalation Challenge in Asthma 总被引:2,自引:0,他引:2
Allergen exposure in atopic asthmatic patients is associated with recruitment and activation of eosinophils in the airways.
Once activated, eosinophils release toxic products, including the eosinophil cationic protein (ECP), able to damage bronchial
structures and to increase bronchial hyperresponsiveness. With this background, the present study was designed to evaluate
whether ECP levels in bronchoalveolar lavage (BAL) fluid could reflect, better than BAL eosinophil counts, the cellular activation
that follows allergen exposure in atopic asthmatics. Twenty-two atopic patients attended the laboratory on two separate days.
On the 1st day, they underwent methacholine (MCh) inhalation challenge to detect the degree of nonspecific bronchial hyperresponsiveness.
On the 2nd day, they underwent fiberoptic bronchoscopy and BAL, at baseline or 4–6 h after allergen inhalation challenge.
In this latter patient group, MCh challenge was repeated 3–5 h after allergen challenge, 1 h before fiberoptic bronchoscopy.
The analysis of the mean baseline FEV1 values and the degree of bronchial reactivity to MCh (MCh Pd20) on the 1st study day did not demonstrate differences between the two patient groups (p > 0.1, each comparison). In addition, in the allergen-challenged group, MCh Pd20 was decreased significantly after allergen challenge (151.4 μg/ml and 67.6 μg/ml, respectively, before and after challenge;
p < 0.05). Evaluation of the different BAL cell types demonstrated that the proportions of eosinophils and epithelial cells
were increased significantly in the allergen-challenged group compared with the group evaluated at baseline (p < 0.01 and p < 0.05, respectively). Moreover, ECP levels, corrected by the correspondent albumin levels (ECP/Alb), were higher in the
allergen-challenged group compared with the group evaluated at baseline (p < 0.05). In addition, although a positive correlation was demonstrated between BAL eosinophil percentages and ECP/Alb values
(r= 0.72, p < 0.05) in the group evaluated at baseline, no links were found between these parameters in the allergen-challenged group
(p > 0.1). However, in this latter group, a weak positive correlation was demonstrated between eosinophil percentages and ΔMch,
i.e., the increased nonspecific bronchial reactivity, which is observed after allergen challenge (r= 0.55; p < 0.05). Thus, in stable asthmatic patients an ongoing activation of eosinophils parallels their migration, but this eosinophilic
inflammation is not strictly related to bronchial reactivity to Mch. By contrast, after allergen inhalation challenge, eosinophil
recruitment and activation seem to follow different temporal kinetics, and eosinophilic inflammation may be partially associated
with the degree of airway hyperresponsiveness.
Accepted for publication: 15 September 1997 相似文献
10.
In this review the effects of oxidant inhalation on the pulmonary surfactant system of laboratory animals are discussed.
Oxidant lung injury is a complex phenomenon with many aspects. Inhaled oxidants interact primarily with the epithelial lining
fluid (ELF), a thin layer covering the epithelial cells of the lung which contains surfactant and antioxidants. In the upper
airways this layer is thick and contains high levels of antioxidants. Therefore oxidant injury in this area is rare and is
more common in the lower airways where the ELF is thin and contains fewer antioxidants. In the ELF oxidants can react with
antioxidants or biomolecules, resulting in inactivation of the biomolecules or in the formation of even more reactive agents.
Oxidation of extracellular surfactant constituents may impair its function and affect breathing. Oxidized ELF constituents
may promote inflammation and edema, which will impair the surfactant system further. Animal species differences in respiratory
tract anatomy, ventilatory rate, and antioxidant levels influence susceptibility to oxidants. The oxidant exposure dose dictates
injury, subsequent repair processes, and tolerance induction.
Accepted for publication: 26 September 1996 相似文献
11.
Surfactant protein A (SP-A) enhances the uptake of phospholipid by type II cells derived from adult and late gestation fetal
rat lung. The present study was performed to examine more fully the developmental biology of the effects of SP-A on phosphatidylcholine
(PC) uptake, to determine the effect of SP-A on the cellular location of bound and internalized phospholipid and on the metabolism
of internalized phospholipid by morphologically undifferentiated (18-day) and morphologically differentiated (19-day) fetal
type II cells. SP-A enhanced uptake almost twofold in a dose-dependent manner in 19-day fetal cells, but it had no effect
on uptake by 18-day fetal cells at any concentration. Stimulation of uptake by 19-day fetal cells was saturable at concentrations
above 1 μg/ml SP-A. Maximal uptake was 1.12 nmol of PC/mg of protein, and the effective concentration that yields 50% maximal
response, KΦ, was 58.9 ng/ml (84.1 pM). The effect of SP-A on uptake by 19-day fetal cells was detectable as early as 1 min of exposure.
Uptake correlated significantly with time both in the absence (r= 0.98, p < 0.001) and presence of 5 μg/ml SP-A (r= 0.979, p < 0.001). The rate of uptake in the presence of SP-A (0.019 ± 0.002 nmol of PC/mg of protein/min) was twice the rate of uptake
in controls (0.009 ± 0.001 nmol of PC/mg of protein/min). SP-A had no effect on binding to plasma membranes and uptake of
phospholipid into lamellar bodies by 18-day fetal cells. On the other hand, SP-A significantly enhanced binding of dipalmitoyl
phosphatidylcholine to plasma membranes (two- to threefold) and uptake into lamellar bodies (threefold) of 19-day fetal cells.
SP-A caused a significant reduction in the degradation of internalized phospholipid by differentiated fetal type II cells.
Based on the lack of effect of exogenous SP-A on 18-day fetal cells, we conclude that the response to SP-A is under developmental
control. SP-A enhances the initial binding to the plasma membranes of fetal type II cells and subsequent internalization into
the lamellar bodies. This effect is associated with a protection of internalized phospholipid from metabolic degradation.
Both of these processes are developmentally regulated during the transition from the canalicular to the saccular phase of
lung development.
Accepted for publication: 15 May 1997 相似文献
12.
Tannin, isolated from cotton bracts and implicated in the pathogenesis of byssinosis, inhibits isoproterenol and forskolin-stimulated
cAMP release from airway cells in part by decreasing cell surface β-adrenergic receptor number and uncoupling the β-adrenergic
receptor from its stimulatory G-protein (Gs) and in part by inhibiting adenylyl cyclase activity. We have hypothesized that cotton tannin, because of its long polymer
length, interacts with the hydrophobic binding pocket of the β-adrenergic receptor and alters β-adrenergic receptor binding
and Gs coupling. In these studies, tannins of three different polymer lengths and molecular masses were isolated from cotton bracts
using sequential Amicon ultrafiltration [molecular mass > 10,000 (YM10 retentate), 1,000–10,000 (YM10 filtrate), and 1,000–5,000
Da (YM2 retentate)]. The YM10 retentate (25 μg/ml) decreased chloride secretion (Jnet = 1.11 ± 0.28 (control) to 0.59 ± 0.18
μEq/cm2·h, p < 0.05, n= 6), decreased cell surface β-adrenergic receptor number (18.0 ± 1.8 (control) to 10.6 ± 0.9 fmol/mg protein, p < 0.02, n= 4), and inhibited forskolin-stimulated cAMP release (5,254 ± 1,290 (control) to 2,968 ± 620 pmol/mg protein, p < 0.01, n= 8). In contrast, neither the YM10 filtrate nor the YM2 retentate had any effect on net chloride secretion, β-adrenergic
cell surface receptor number, or forskolin-stimulated cAMP release. We conclude that polymer length is essential for the effect
of tannin on the β-adrenergic receptor and on adenylyl cyclase.
Accepted for publication: 28 June 1998 相似文献
13.
14.
Ishii Y Hashimoto K Hirano K Morishima Y Mochizuki M Masuyama K Nomura A Sakamoto T Uchida Y Sagai M Sekizawa K 《Lung》2000,178(4):225-234
We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen
every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased
pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage
fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible
nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting
that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the
pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also
contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents
a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.
Accepted for publication: 8 May 2000 相似文献
15.
To determine the site of action of inhaled nitric oxide (iNO) in the newborn pig lung, lungs were isolated and perfused at
constant flow for microfocal x-ray angiography. Measurements of pulmonary arterial diameters were made on arteries in the
100–2500 μm diameter range under control conditions, during vasoconstriction caused by hypoxia (decreasing PO2 from ∼120 to ∼50 Torr), or Nω-nitro-L-arginine methylester (L-NAME 10−4 M) administration, with or without vasodilation induced by iNO (40 ppm) or by the NO donor S-nitroso-N-acetylpenicillamine
(SNAP 5 × 10−6 M) given intravascularly. Hypoxia caused constriction only in smaller arteries whereas L-NAME constricted arteries throughout
the size range studied. iNO dilated the smaller arteries more than the larger arteries under all study conditions. SNAP was
used to provide an intravascular source of NO for comparison to iNO. SNAP also dilated smaller arteries more than larger arteries,
but it had a significantly greater effect on the large arteries than did iNO. This suggests that differential accessibility
of the vascular smooth muscle to NO between sources, air and blood, is a factor in the diameter dependence of the responses.
Accepted for publication: 13 March 2001 相似文献
16.
X. L. Qiu L. V. Brown S. Parameswaran V. W. Marek G. S. Ibbott S. J. Lai-Fook 《Lung》1999,177(5):273-288
Albumin diffusion measured in an isolated segment of rabbit lung interstitium with a radioactive tracer (125I-albumin) technique was independent of albumin concentration and similar to the free diffusion of albumin in water (Qiu et
al, 1998. J Appl Physiol 85: 575–583). We studied the effect of hyaluronidase on the diffusion of albumin. Isolated rabbit
lungs were inflated with silicon rubber by way of airways and blood vessels, and two chambers were bonded to the sides of
a ∼0.5-cm thick slab enclosing a vessel with an interstitial cuff. One chamber was filled with 2 g/dl albumin solution containing
125I-albumin and 0.02 g/dl hyaluronidase. Unbound 125I was removed from the tracer by dialysis before use. The other chamber filled with Ringer's solution was placed within a
NaI(Tl) scintillation detector. Diffusion of tracer was measured continuously for 120 h. Albumin diffusion coefficient (D)
and interstitial area (A) were obtained by fitting the tracer-time curve with the theoretical solution of the equation describing
one-dimension diffusion of a solute across a membrane. D averaged 5.2 × 10−7 cm2/s for albumin diffusion with hyaluronidase, 20% less than that measured previously without hyaluronidase. Hyaluronidase had
no effect on A. Results indicated an interaction between albumin and interstitial hyaluronan that was the opposite of the
steric effect on albumin excluded volume measured in solution.
Accepted for publication: 9 May 1999 相似文献
17.
Lung tissue resistance (Rti) measured in air-filled guinea pig lungs by the alveolar capsule technique was a large part of total lung resistance (Rl), and we wondered whether similar results applied to saline-filled lungs. We used the micropuncture method to measure alveolar
pressure (Palv) in saline-filled lungs of 21 guinea pigs. Palv and airway opening pressure (Pao) were measured before and after a sudden interruption of flow during an inflation or deflation maneuver. On stopping flow,
there was an immediate large change in Pao followed by a smaller slower change in Pao. Palv was nearly constant immediately after flow interruption but followed the slower change in Pao. The initial change in Pao on flow interruption was interpreted as the resistive pressure loss in the airways. The small change in Pao and Palv was interpreted as the pressure loss caused by tissue stress adaptation. Airway resistance (Raw) and Rti were obtained by dividing the pressure losses by the flow before the interruption. Rl was the sum of Raw and Rti. The calcium blocker nifedipine reduced both Raw and Rti and abolished the difference in Rti between inflation and deflation. Values of Rti were 10–29% of Rl. However, with correction for viscosity, Rti predicted in air-filled lungs would dominate Rl.
Accepted for publication: 21 February 1997 相似文献
18.
Silica inhalation predisposes workers to bacterial infection and impairments in pulmonary defense function. In this study,
we evaluated the effect of pre-exposure to silica on lung defense mechanisms by use of a rat pulmonary Listeria monocytogenes infection model. Male Fischer 344 rats were exposed by inhalation to filtered air or silica (15 mg/m3× 6 h/day × 5 days/wk). After 21 or 59 days of silica exposure, the rats were inoculated intratracheally with 5 × 103
L. monocytogenes. At 0 (noninfected controls), 3, and 7 days after infection, the left lungs were removed, homogenized, and the number of
viable L. monocytogenes was counted after an overnight culture at 37° C. Bronchoalveolar lavage (BAL) was performed on the right lungs. Alveolar
macrophages (AM) were collected, and the AM production of chemiluminescence (CL), an index of reactive oxygen species generation,
was measured. The number of lavagable neutrophils (PMNs) and acellular BAL lactate dehydrogenase (LDH) activity were determined
as indices of inflammation and injury, respectively. Pre-exposure to silica for 59 days caused substantial increases in PMN
number and LDH activity compared with the air controls, whereas silica inhalation for both 21 and 59 days significantly enhanced
the pulmonary clearance of L. monocytogenes compared with air controls. Dramatic elevations were also observed in zymosan- and phorbol myristate acetate (PMA)–stimulated
CL production by lung phagocytes recovered from rats pre-exposed to silica for 59 days. These results demonstrate that short-term
exposure to inhaled silica particles activates lung phagocytes, as evidenced by increases in reactive oxygen species. This
up-regulation in the production of antimicrobial oxidants is likely responsible for the enhancement in pulmonary clearance
of L. monocytogenes observed with short-term silica inhalation.
Accepted for publication: 2 October 2000 相似文献
19.
B. A. Zachara E. Marchaluk-Wiśniewska A. Maciag J. Pepliński J. Skokowski W. Lambrecht 《Lung》1997,175(5):321-332
We studied the selenium (Se) concentration in whole blood and plasma, glutathione peroxidase (GSH-Px) activity in red blood
cells and plasma, as well as both of these parameters in cancerous and tumor-free lung tissue of lung cancer patients. Blood
samples were taken from 84 cancer patients and 61 healthy controls. Normal and neoplastic lung tissues were obtained from
57 patients at the time of surgery. Se concentrations in whole blood and palsma were lower by 23% (p < 0.001) in patients compared with controls. GSH-Px activity in red cells was lower by 20.2% (p < 0.004) and in plasma by 11.7% (p < 0.05) in patients than in the control group. On the other hand, the tumor Se level was higher by 66.6% (p < 0.0001) and GSH Px activity by 49.5% (p < 0.0001) than in adjacent tumor-free tissue. No differences in Se concentrations and GSH-Px activities were found between
squamous cell carcinoma and adenocarcinoma nor among the clinical stages of the disease. In the whole blood and plasma of
cancer patients significantly lower Se concentrations were found in smokers than in nonsmokers. Significantly lower Se concentrations
were also found among cancer patients who were smokers compared with controls. These findings show that in the blood of cancer
the antioxidant ability, as measured by Se and GSH-Px, is reduced significantly. The cause of increased Se and GSH-Px in the
malignant part of the lung is not understood and requires further studies.
Accepted for publication: 17 April 1997 相似文献
20.
We have shown recently that apoptosis occurs during fetal and postnatal lung development. Our hypothesis that branching morphogenesis
occurs through a delicate balance of cell proliferation and apoptosis predicts that substances that enhance branching of the
airways would affect both cell proliferation and apoptosis in the lung. Bombesin-like peptides have a mitogenic effect on
bronchial epithelium and fibroblasts, and bombesin has been shown to enhance branching morphogenesis in fetal lung. We used
organ cultures of 16-day gestation fetal rat lung to study the effects of bombesin on apoptosis. Cultures were incubated in
serumless medium alone or exposed to 1μM bombesin for 0–48 h. Levels of apoptosis were quantified using the TUNEL assay and
expressed as percentage of apoptotic cells in paraffin sections of explants. Bombesin significantly inhibited apoptosis in
fetal lung mesenchyme 48 h in culture by more than 50% (p < 0.05). The effects of bombesin on apoptosis were prevented completely if explants were exposed to the specific bombesin
receptor antagonist, [d-Phe12]bombesin. To examine if the absence of serum in the media could have accounted for some of these effects, explants were cultured
for 48 h in serumless medium, medium containing 10% fetal bovine serum, serumless medium with 1 μM bombesin, or medium containing
both 10% fetal bovine serum and 1 μM bombesin. The addition of fetal bovine serum to the media reduced apoptosis significantly.
The effect of fetal bovine serum on apoptosis was additive with bombesin. We conclude that bombesin inhibits apoptosis in
developing fetal rat lung mesenchyme through its interaction with the bombesin receptor.
Accepted for publication: 18 March 1999 相似文献