Intratracheal Application

Nechev H, Sulovski P, Shopova Y, et al. 1982. Particularities in the metabolism of americium-241 after intratracheal application and in combination with external irradiation. Sci Works Higher Med Inst-Pleven 4(l) 37-43. 

Biesalski, FI. K. (1996). Effects of intratracheal application of vitamin A on concentrations of retinol derivates in plasma, lungs and selected tissue of rats. Int. ]. Vitam. Nutr. Res. 66, 106-112. 

The tissue distribution of 2,3,7,8-TCDD-derived radioactivity was recently examined in male Fischer 344 rats 3 days after intratracheal application of a single dose of 0.32 g 2,3,7,8-TCDD/kg (Diliberto et al. 1996). The liver and adipose tissue were the major tissue depots for 2,3,7,8-TCDD-derived radioactivity with 33 and 15% of the applied dose distributing to these respective tissues. The skin (ear) and muscle followed with 4.3 and 1.3%, respectively. All other tissues had less than 0.5% of the administered dose. The 2/1 liver/adipose ratio was in contrast to the approximately 1/1 ratio found after gavage administration of the same dose. 

Pharmacokinetic studies in several animal species (see Table 3) have shown that nonglycosylated recombinant ai-PI has a much shorter plasma half-life than the native form of ai-PI (1-2 hours vs. 2-4 days) [61,62]. Since the proposed mode of delivery of ai-PI is by aerosolization, rapid plasma elimination should not be a concern. It has been demonstrated that both recombinant and native at-PI can be aerosolized without loss of inhibitory activity and animal studies have shown that aerosolized at-PI has an extended lung half-life. We have also investigated the pharmacokinetics of recombinant ai-PI in rat. The distribution and elimination half-life after bolus intravenous application of 2 mg/kg were approximately 25 and 100 minutes, respectively. After intratracheal application of recombinant ai-PI, plasma levels peaked between 4 and 8 hours after administration, and the half-life of disappearance from the lung was approximately 12.5 hours as measured by ELISA and 11 hours as determined by antielastase activity. This confirms that ai-PI administered to the lung remains active for an extended period of time and is able to cross from the lung into the blood. Low amounts of... 

The specific effect of beryllium in DNA metabolism may be highly relevant in the elucidation of its experimentally demonstrated carcinogenic action. Primary tumours of the lung in rats typically occur 8 months after intratracheal application. Either a single tumour or multiple tumours may be formed. Histologically those are adenomas, less frequently epitheliomas. By the action on beryllium, certain enzymes were affected, as in other experiments on animals, where the cancer disease was induced by different... 

The addition of absorption enhancers, like bile salts (glycocholate), fatty acids (Unoleic acid), surfactants (lecithins, polyoxyethylene-9-lauryl ether or N-lauryl-P-D-maltopyra-noside) and chelators (EDTA) can significantly increase the absorption of various proteins. However, the application of enhancers is limited by their toxicity. For example polyoxyethyl-ene-9-lauryl ether and sodium glycocholate caused serious oedema, haemorrhage and inflammation of the lung after intratracheal instillation [39]. 

Preussmarm, R., Spiegelhalder, B., Eisenbrand, G, Wrirtele, G Hofmarm, I. (1981) Urinary excretion of V-nitrosodiethanolamine in rats following its epicutaneous and intratracheal administration and its formation in vivo following skin application of diethanolamine. Cancer Lett., 13, 227-231... 

Pour, P. Wallcave, L. (1981) The carcinogenicity of A -nitrosodiethanolamine, an environmental pollntant, in Syrian hamsters. Cancer Lett, 14, 23-27 Preussmann, R., Wiirtele, G, Eisenbrand, G Spiegelhalder, B. (1978) Urinary excretion of A -nitrosodiethanolamine administered orally to rats. Cancer Lett, 4, 207-209 Preussmann, R., Spiegelhalder, B., Eisenbrand, G, Wiirtele, G Hofmann, I. (1981) Urinary excretion of A -nitrosodiethanolamine in rats following its epicutaneous and intratracheal administration and its formation in vivo following skin application of diethanolamine. Cancer Lett, 13, 227-231... 

Studies of the carcinogenicity of chloroprene by the oral route or inhalation, intratracheal administration, subcutaneous or intramuscular injection or skin application were reviewed by lARC (1979) and found inadequate for evaluation. These studies are not considered further. 

The final steps to a synthetic blood depend completely upon good chemistry tailored to meet the exact needs of the body Fluorocarbons, such as perfluorodecalin, recently have been found to induce hypennflated lungs when given either intravenously as an emulsion or intratracheally as a neat liquid [/, 19 But this and other physiological side effects are now understood, and research is well advanced to prevent undesirable side effects in medical applications of fluorocarbon liquids... 

Grimmer G, Brune H, Dettbarn G, et al. 1988. Urinary and faecal excretion of chrysene and chrysene metabolites by rats after oral, intraperitoneal, intratracheal or intrapulmonary application. Arch Toxicol 62(6) 401-405. 

Since recombinant SLPI is identical to the native inhibitor, allergenic reactions are not to be expected with this molecule. A one-month toxicity study after aerosol application of recombinant SLPI in cynomolgus monkeys has been performed with no clinically relevant toxicity observed [7]. Intratracheal pretreatment of hamsters with recombinant SLPI (3 mg) resulted in significant protection against NE-induced emphysema even if the animals were pretreated for as long as 8 hours before elastase instillation [79]. Therefore, recombinant SLPI appears to be a safe and effective inhibitor. 

The toxicity of palytoxin via several other routes of administration has been investigated (Table 32.7). This substance is highly toxic after intramuscular or subcutaneous injection, or following intratracheal instillation [90,96]. No toxicity was recorded after intrarectal administration of palytoxin at 10 [tg/kg [90]. Renal necrosis and pulmonary damage were recorded in animals given palytoxin intradermally [96], and local irritation and swelling, associated with edema and necrosis, were observed after both intradermal injection and percutaneous application. Severe irritation, involving ulceration and conjunctivitis, was induced by application of palytoxin to the eye [96]. 

Fig. 76. Plenty of endoplasmic reticulum and polysomes in the apici part of a Clara cell from a female rat (breeder Winkelmann, Borchen-Kirchborchen), which received daily intragastric applications of 82 mg retinol pal-mitate per kg body weight x day, 5 days per week from April 17 to June 20, 1967 for a total of 42 days. Fixed on June 20, 1967 under methitural anaesthesia by intratracheal instillation of 2.5 % glutarddehyde in phosphate buffer (pH 7.4) before opening the thorax. After waging in phosphate buffer the tissue was postfixed with 1 % osmium te-troxide in phosphate buffer for 2 h. Contrasted enbloc for 12 h with 0.5% uranyl acetate in 70 % ethanol. Embedded in a 2 8 mixture of methyl and butyl methacrylate. Sectioned at 50 nm. Lead citrate after Reynolds (1963). Plate 12/07...

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