Three pulmonary surthctant preparations: from human amniotic fluid, from bronchoalveolar lavage fluid, and from cattle lung tissue homogenate were tested in preclinical studies. The preparations are nontoxic, possess no mutagenic, teratogenic, and allergic activities and do not modify visceral morphology after repeated injections. After a single intratracheal administration the drugs normalize arterial blood oxygenation in 15-30 rain and arrest the respiratory distress syndrome in dogs, which is confirmed roentgenologically and clinically.
Key Words: respiratory distress syndrome; surfactant; pharmacological properties; therapeutic activityThe respiratory distress syndrome (RDS) is one of the major causes of neonatal and adult mortality [3,5]. About 30,000 babies with RDS are annually born in Rnssia; in the USA 150,000 RDS cases are recorded annually in adults. In RDS 15-30% newborns and 50-70% adults die [3,5,7]. In preterm newborns RDS is caused by immaturity of type 2 alveolocytes and the resultant primary deficiency of puhnonary surthctant (PS) [2]. In RDS of adults, PS deficiency is secondary, developing as a result of structural and functional disorders in the airblood barrier. It often develops after multiple injury, sepsis, shock lung, radiation injury, etc. Natural and synthetic PS preparations have been widely used all over the world: smwana (USA), surfactant-TA (Japan), curosurf (Italy), alveofact (Germany), exosurf (UK) [8].We developed a technologically inexpensive method for preparing natural PS and chalacterized their physicochemical properties. Three preparations were studied: human PS isolated from parturients' amniotic fluid, PS from bronchoalveolar iavage fluid (PS-BLF), and PS prepared by water-salt extraction of finely dispersed cattle lung (PS-WSE).The pharmacological and therapeutic properties of these PS preparations are studied.
A method for experimental reproduction of stages of chronic obstructive pulmonary disease formation (from acute inflammation to bronchopulmonary tissue restructuring characteristic of this disease) is presented. Lung injury and inflammation were induced by nitrogen dioxide. Hyperplasia and hypersecretion of goblet cells, squamous cell metaplasia of the ciliary epithelium, emphysema, and focal fibrosis served as the morphological substrate for the formation of bronchial obstruction. The adequacy of the model is confirmed by signs characteristic of chronic obstructive pulmonary disease: hyperexpression of CD3 lymphocytes in the bronchial wall and parenchyma, manifold increased production of TNFα and TGFβ, high concentrations of circulating pathogenic immune complexes. Persistence of the structural and functional shifts throughout 6 months after exposure to nitrogen dioxide indicated a chronic course of the resultant pathological process.
Afterintratracheal administration of "empty" lecithin-cholesterol liposomes to rats it was found out twofold enhancement of the surfactant content with maximum on the 2nd-3rd day and with normalization to the the alveolar macrophages was also increased.It was shown the change of the blast-transformation reaction of bronchoalveolar lavage and blood lymphocytes. Immune complexes content in bronchoalveolar lavage at different period of time after liposomes administration increased 1.5-2-fold. The natural killers (NK) activity of cells obtained from bronhoalveolar lavage and blood was enhanced 10 times and 2 times respectively. It is supposed that enhancement of lung surfactant phospholipid content is caused by substrate stimulation of type I1 alveolocytes activity. The stimulation of immunocompetent cells might be connected with imitation of bacterial attack by liposomes with proteins adsorbed on their surface. control level by the 7th day. Phagocytic index of 203 Copyright 0 1994 by Marcel Dekker, Inc. Journal of Liposome Research Downloaded from informahealthcare.com by McMaster University on 12/08/14 For personal use only. IBb Re1.u. 4.7fO .8 + 4.2-0.3 7. 5+0. + 7.2-0.5 7. lfl. 2 5.4*0.6 Journal of Liposome Research Downloaded from informahealthcare.com by McMaster University on 12/08/14 For personal use only.
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