scholarly journals Impact of simulated lung fluid components on the solubility of inhaled drugs and predicted in vivo performance

2021 ◽  
pp. 120893
Author(s):  
Snezana Radivojev ◽  
Gerfried Luschin-Ebengreuth ◽  
Joana T. Pinto ◽  
Peter Laggner ◽  
Alessandro Cavecchi ◽  
...  
Keyword(s):  
Inhaled Drugs ◽  
Lung Fluid ◽  
Simulated Lung Fluid

Involvement of αENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis

2007 ◽  
Vol 293 (4) ◽  
pp. L1069-L1078 ◽  
Author(s):  
Tianbo Li ◽  
Shyny Koshy ◽  
Hans G. Folkesson
Keyword(s):  
Extravascular Lung Water ◽  
Fluid Secretion ◽  
Alveolar Epithelial Cells ◽  
Na Channel ◽  
Fluid Absorption ◽  
Lung Water ◽  
Fourfold Increase ◽  
Lung Fluid ◽  
Near Term

To explore interactions between the epithelial Na channel (ENaC) and neural precursor expressed, developmentally downregulated protein 4-2 (Nedd4-2) at the conversion of the rat lung from fluid secretion to absorption at birth, we used small-interfering RNA (siRNA) against αENaC and Nedd4-2. siRNA-generating plasmid DNA (pDNA) was administered via trans-thoracic intrapulmonary (ttip) injection 24 h before ENaC and Nedd4-2 expression, extravascular lung water, and mortality were measured. αENaC mRNA and protein were specifically reduced by ∼65% after pSi-4 injection. Nedd4-2 mRNA and protein were reduced by ∼60% after pSi-N1 injection. Interestingly, αENaC and βENaC mRNA and protein expression were increased after Nedd4-2 silencing. Extravascular lung water was significantly increased after αENaC silencing and reduced after Nedd4-2 silencing. αENaC silencing resulted in a fourfold increase in newborn mortality, whereas silencing Nedd4-2 did not affect mortality. We also isolated distal lung epithelial (DLE) cells after in vivo αENaC or Nedd4-2 silencing and measured αENaC or Nedd4-2 expression in freshly isolated DLE cells. In these DLE cells, there were attenuated αENaC or Nedd4-2 mRNA and protein, thus demonstrating that αENaC and Nedd4-2 silencing occurred in alveolar epithelial cells after ttip injection. We also looked for pDNA by PCR to determine pDNA presence in the lungs and found strong evidence for pDNA presence in both lungs. Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.

Mechanisms and sequelae of increased alveolar fluid clearance in hyperoxic rats

1997 ◽  
Vol 272 (3) ◽  
pp. L407-L412 ◽  
Author(s):  
G. Yue ◽  
S. Matalon
Keyword(s):  
Alveolar Epithelial Cells ◽  
Na Channels ◽  
Alveolar Fluid Clearance ◽  
Na Transport ◽  
Alveolar Epithelial ◽  
Lung Fluid ◽  
Isotonic Fluid ◽  
Epithelial Na Channels ◽  
Alveolar Edema

We instilled 4 ml isotonic fluid containing trace amounts of fluorescently labeled dextran (molecular mass 150 kDa) in the lungs of rats exposed to either 85% O(2) for 7 days or to 85% O(2) for 7 days and 100% O(2) for 3 days. We withdrew the fluid every hour for a 3-h period and calculated alveolar fluid clearance (AFC) from changes in dextran concentration. Postinstillation (3 h), AFC values in the control and the two hyperoxic groups were 51 +/- 1, 63 +/- 2, and 62 +/- 3 (SE), respectively (%instilled volume; n > or = 5; P < 0.05). Addition of either 1 mM amiloride or N-ethyl-N-isopropyl amiloride (EIPA) in the instillate decreased the AFC values in all groups 3 h later to approximately 30% of instilled volume. Instillation of phenamil, an irreversible blocker of epithelial Na+ channels into the lungs of rats exposed to 85% O(2) for 7 days and 100% O(2) for 2 days, resulted in a significant increase of their extravascular lung fluid volumes 24 h later. These results demonstrate the existence of EIPA-inhibitable Na+ channels in alveolar epithelial cells in vivo and indicate that an increase in Na+ transport plays an important role in limiting the amount of alveolar edema in O(2)-damaged lungs.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

scholarly journals Size Distribution, Bioaccessibility and Health Risks of Indoor/Outdoor Airborne Toxic Elements Collected from School Office Room

Atmosphere ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 340 ◽  
Author(s):  
Zhi-Jie Tang ◽  
Xin Hu ◽  
Jun-Qin Qiao ◽  
Hong-Zhen Lian
Keyword(s):  
Size Distribution ◽  
Health Risks ◽  
Toxic Elements ◽  
Inhalation Exposure ◽  
Potential Health ◽  
Lung Fluid ◽  
Mass Size ◽  
Office Rooms ◽  
Simulated Lung Fluid ◽  
Indoor And Outdoor

20 sets of indoor and outdoor size-segregated aerosol (SSA) samples (180 foils) were collected synchronously by using two 8 Stage Non-Viable Cascade Impactor from an office room in the central region of the megacity-Nanjing, China in winter and spring in 2016. The mass size distribution of SSAs was bimodal for outdoor SSAs and unimodal for indoor in both winter and spring. The crustal elements, such as K, Ca, Mg and Fe, were mainly distributed in the coarse fractions of SSAs while toxic elements such as As, Cd, Pb and Sb were enriched more in the fine fractions in both winter and spring. Moreover, indoor/outdoor (I/O) concentration ratios of SSAs and inorganic elements indicated the penetration of outdoor fine fractions of SSAs into indoor air. As, Pb, V and Mn showed higher inhalation bioaccessibility extracted by the artificial lysosomal fluid (ALF); while V, As, Sr and Cd showed higher inhalation bioaccessibility using the simulated lung fluid (SLF), suggesting differences in elemental inhalation bioaccessibility between ALF and SLF extraction. There were similar potential carcinogenic and accumulative non-carcinogenic risks via inhalation exposure to indoor and outdoor particle-bound toxic elements based on their bioaccessible concentrations. Therefore, the potential health risks to human posed by toxic elements in office rooms cannot be neglected via inhalation exposure of the fine airborne particles.

Temperature affects lung fluid and recoil during high tidal ventilation at low resting volume

1987 ◽  
Vol 63 (5) ◽  
pp. 1705-1710
Author(s):  
T. Horie ◽  
T. Izumi ◽  
K. Hodaka ◽  
T. Akashiba ◽  
Y. Hosokawa ◽  
...  
Keyword(s):  
Activity Index ◽  
Weight Ratio ◽  
Dry Weight ◽  
Elastic Recoil ◽  
Edema Formation ◽  
Lung Fluid ◽  
Open Chest ◽  
Tidal Ventilation ◽  
Minimum Surface Tension

Effects of tidal volume (VT), end-expiratory pressure (EEP), and environmental temperature (Tenv) on elastic recoil force (Pel) and edema formation were examined in open-chest anesthetized rabbits. Sixty-two rabbits in four groups were ventilated for 3 h with VT of either 10 or 25 ml/kg body wt, EEP of 0 or 2 cmH2O, and Tenv of 18 or 35 degrees C. After ventilation, Pel at 80% of total lung capacity (P80) was significantly increased when ventilation was performed with the combination of large VT, 0 EEP, and low Tenv. This change was prevented by altering any one of the three conditions, e.g., small VT, positive EEP, or high Tenv. Similarly, elevation of minimum surface tension and reduction of surface activity index of lavages from excised lungs after ventilation were observed only when increased P80 was noted. Additionally, the increase of P80 was well correlated with increment of wet weight-to-dry weight ratio and degree of perivascular cuffing and alveolar edema formation of excised lungs. These results indicate that elevation of Pel after high tidal ventilation in open-chest animals in vivo was influenced by level of EEP and Tenv and that the degree of edema formation was closely related to the increase of Pel. The increased Pel is presumably primary and causes fluid accumulation.

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