Epithelia pulmonary epithelium

Intraspecies Because the species used was the most sensitive to monomethylhydrazine toxicity and the most closely related to humans, an uncertainty factor of 3 is justified. A factor of 3 was used. Although the mechanism of toxicity is uncertain and sensitivity among individuals may vary, the exposure-response relationship is steep, suggesting limited variability in the toxic response to methylhydrazine. Furthermore, it is likely that acute toxic responses are, at least initially, a function of the extreme reactivity of methylhydrazine. The interaction of the highly reactive monomethylhydrazine with tissues (e.g., pulmonary epithelium) is not likely to greatly vary among individuals. 

Keywords Bronchial epithelium Pulmonary drug absorption Pulmonary metabolism Drug transport Permeability... 

Thompson AB, Robbins RA, Romberger DJ, Sisson JH, Spurzem JR, Teschler H, Rennard SI (1995) Immunological functions of the pulmonary epithelium. Eur Respir J 8(1) 127—149. 

In relation to the above it is obvious that passage of the pulmonary epithelium may depend on characteristics of a drug molecule. Not only the size, but also its solubility, overall charge, structural conformation and potential aggregation can have a significant effect on the absorption rate and bioavailabUity of the drug after pulmonary deposition. 

In most organs and tissues the injury and the underlying mechanism for that injury are complex and may involve a combination of events. The extent and severity of this tissue injury are dependent upon the radiosensitivity of the various cell types in that organ system. Rubin and Casarett (1968) describe and schematically display the events following radiation in several organ system types. These include a rapid renewal system, such as the gastrointestinal mucosa a slow renewal system, such as the pulmonary epithelium and a nonrenewal system, such as neural or muscle tissue. In the... 

The main drugs in this group are lomustine, carmustine, semustine and streptozotocin. The nitrosoureas are lipophilic and cross the blood-brain barrier. They are therefore effective against brain tumours. They cause a severe cumulative bone marrow depression that starts within 1-2 months of treatment. Lomustine and carmustine cause direct injury to the pulmonary epithelium leading to alveolar fibrosis. Streptozotocin has little bone marrow toxicity, but destroys the pancreatic 3 cells, causing diabetes mellitus. 

One of the main drivers for the development of new pulmonary drug delivery systems has been the potential for noninvasive systemic delivery of protein and peptide compounds. The systemic delivery of macromolecules via the airways would overcome the inconvenience and cost associated with current methods of administration (injection), and appears likely given the large surface area of the airways and the thin pulmonary epithelium. Most research has concentrated on pulmonary delivery of insulin for the treatment of diabetes. Recently, one insulin product has completed phase three studies and is now undergoing review by European regulatory agencies for marketing approval. 

P. Briscoe, I. Caniggia, A. Graves, B. Benson, L. Huang, A. K. Tanswell, and B. A. Freeman, Delivery of superoxide dismutase to pulmonary epithelium via pH-sensitive liposomes, Am. J. Physiol. 26 L374 (1995). 

H.P. Schnebli, R.C. Thompson, and R.G. Crystal. 1990. Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. /. Appl. Physiol. 69 1843-1848. 

Pulmonary epithelium at three principal levels bronchus, bronchiolus and alveolus... 

Inhalation Inhalation provides the rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium, producing an effect almost as rapidly as by intravenous injection. This route of administration is used for drugs that are gases (for example, some anesthetics), or those that can be dispersed in an aerosol. The route is particularly effective and convenient for patients with respiratory complaints (for example, asthma or chronic obstructive pulmonary disease) as drug is delivered directly to the site of action and systemic side effects are minimized (see p. 219). 

Finally, an increased secretory activity of the pulmonary epithelium was observed. 

More sophisticated techniques than the ones used by Haldane have estabhshed that CO binds to hemoglobin with an affinity 200 times greater than that of oxygen (Ernst and Zibrak, 1998 Roughton and Darling, 1944 Sendroy et al, 1930). Carbon monoxide diffuses from the alveoh to the blood in pulmonary capillaries across the alveoh-capillary membrane, which is composed of pulmonary epithelium, the capillary epithelium, and the fused basement membranes of the two. The uptake of CO by Hb is very rapid and the transfer of CO is diffusion limited (Prockop and Chichkoa, 2007). 

The uptake of ozone relates directly to its reactions with substrates present in the lung lining fluid, a mechanism referred to by Postlewaite as reactive absorption [3]. The uptake of ozone is thus related not only to its concentration but also availability of substrates within the RTLF [4]. As these are numerous, ozone does not actually transit RTLF and hence cannot interact directly with the pulmonary epithelium. Rather it is consumed during reactions with compounds in this compartment (Fig. 2). Therefore, cellular responses to ozone are not a result of the direct reaction of ozone with cell surface component/receptors but rather are mediated through a cascade of secondary, free radical derived, ozonation products [2,4]. 

Potential sources of NO in the lungs include activated alveolar macrophages, neutrophils alveolar type II cells endothelial cells and airway cells. nNOS is localized to nonadrenergic/noncholinergic nerve terminals and is present in human airway epithelial cells. eNOS is localized to human pulmonary epithelium and bronchial epithelium. Studies have suggested that iNOS is constitutively expressed in human upper airway epithelium... 

Relative to the gastrointestinal mucosa the pulmonary epithelium possesses a high permeability to water soluble molecules, which is an advantage with dmgs such as sodium cromoglicate (IX), a bischromone with two carboxylic acid groups and a pK of approximately 1.9. The dmg is well absorbed from the... 

Drugs may be administered directly into the respiratory tract for activity on, or through, the pulmonary epithelium and mucous membranes. Access to the systemic circulation is relatively enhanced and rapid following administration by this route because the pulmonary surface area is large. A drug solution can be administered as an aerosol that is inhaled. The advantage of this route of administration is the almost instantaneous... 

In animals, HCl is a severe irritant of the eyes and respiratory system. The 30 min LC50 values in rats and mice are 4701 and 2644 ppm, respectively. Animals exposed to high concentrations of HCl gas developed necrosis of the tracheal and bronchial epithelium, pulmonary edema, atelectasis, emphysema, and damage to the pulmonary blood vessels and liver. Chronic exposure to 10 ppm for 6hday for life did not cause neoplastic lesions or serious irritant effects in the nasal epithelium of rats. In experimental animals, exposure to a concentration of 1350 ppm hydrogen chloride gas caused clouding of the cornea after 1.5 h and exposure to 3000 ppm for 6 h caused slight erosion of the corneal epithelium. 

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