Natural Lung Surfactant

One enzyme present in the surfactant fluid is an acid phosphatase able to hydrolyze phosphatidylglycerol phosphate, perhaps functioning in the final step of biosynthesis of the phosphatidylglycerol present in the surfactant.6 Study of the action of the natural lung surfactant has led to development of artificial surfactant mixtures that are being used effectively to save many lives.d... 

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

There is a clinical need for non-natural, functional mimics of the lung surfactant (LS) proteins B and C (SP-B and SP-C), which could be used in a biomimetic LS replacement to treat respiratory distress syndrome (RDS) in premature infants [56]. An effective surfactant replacement must meet the following performance requirements (i) rapid adsorption to the air-liquid interface, (ii) re-spreadabihty... 

Lung surfactant is composed mainly of lipid with some proteins and carbohydrate and prevents the alveoli from collapsing. Surfactant activity is largely attributed to dipalmitoylphosphatidylcholine, which is synthesized shortly before parturition in full-term infants. Deficiency of lung surfactant in the lungs of many preterm newborns gives rise to respiratory distress syndrome. Administration of either natural or artificial surfactant has been of therapeutic benefit. 

No studies were located regarding absorption in humans or animals after inhalation exposure to 2,3-benzofuran. The partitioning of 2,3-benzofuran between particulate matter and synthetic alveolar surfactant in vitro was reported to depend upon the chemical nature of the particles (Sehnert and Risby 1988). Synthetic lung surfactant was able to dissolve 2,3-benzofuran adsorbed to particles with few active sites, but not 2,3-benzofuran adsorbed to particles with many active sites (Sehnert and Risby 1988). These data indicate that inhalation of particles containing 2,3-benzofuran would result in some absorption, depending on the nature of the particles. 

Most materials used to produce liposomes are derived from natural materials, thus are thought to be safe when administered. Generally, however, phospholipids administered in liposomal form are cleared from the lungs more slowly than comparable doses of lung surfactant (Oguchi et al. 1985). Many macromolecules have been incorporated into liposomes in order to improve their pulmonary delivery. Some lipid-entrapped macromolecules have been tested in animal models and human volunteers to determine efficacy (Kellaway and Farr 1990). 

There are also several examples of natural surfactants and foams in the human body. The understanding of the pulmonary surfactant system, although discovered in 1929, has only been applied clinically since about 1990 for the treatment of respiratory distress syndrome. Surfactant replacement therapy may also be used in treating other forms of lung disease, such as meconium aspiration syndrome, neonatal pneumonia and congenital diaphragmatic hernia [881]. Lung surfactant, composed of phospholipids and proteins [882,883], is necessary to maintain a low surface tension at the alveolar air-liquid interface. When there is a deficiency of surfac-... 

Lung surfactant decreases the surface tension and thereby maintains the morphology and function critical for respiration. Deficiency of surfactant in the newborn infant is a condition known as respiratory distress syndrome (RDS) and in adults as adult respiratory distress syndrome (ARDS). A number of commercial artificial surfactants, e.g. Exosurf and ALEC, together with natural surfactant preparations, e g. Surventa and Curosurf, are currently available to treat these conditions. 

Thyroid hormones also accelerate fetal lung maturation. Fetal thyroid hormone levels may be increased by antenatal administration of thyrotropin-releasing hormone (TRH), a tripeptide that crosses the placental barrier, stimulates fetal pituitary production of thyroid stimulating hormone (TSH), and which, in turn, increases fetal thyroid hormone production (Chapter 33). This indirect method of enhancement of fetal thyroid hormone production is utilized because thyroid hormones do not readily cross the placental barrier. Insulin delays surfactant synthesis and so fetal hyperinsulinemia in diabetic mothers may increase the incidence of RDS even in the full-term infant. Androgen synthesized in the fetal testis is the probable cause of a slower onset of surfactant production in male fetuses. Prophylactic, or after onset of RDS, administration of synthetic or natural pulmonary surfactants intratracheally to preterm infants improves oxygenation and decreases pulmonary morbidity. 

Calfactant is a lung surfactant. It is an extract of natural surfactant from calf lungs that restores lung surfactant in premature infants with lung surfactant deficiency causing respiratory distress syndrome (RDS). Calfactant is indicated in RDS in premature infants under 29 weeks of gestational age at high risk for RDS and for the treatment rescue of premature infants under 72 hours of age who develop RDS and require endotracheal inmbation. 

Another important natural protein surfactant in mammalian are lung surfactants, which are secreted by type II pneumocytes and reduce surface tension at the air-water interface of distal airways and the alveoli of lungs, thereby decreasing the work of breathing and the tendency for alveoli to collapse at low lung volumes. The components of lung surfactants as well as the structure and functions of surfactant proteins have been precisely reviewed recently [62]. 

Our lungs use small air sacs, like balloons, to breathe.These air sacs are coated with water and a natural surfactant. Water has a high surface tension, so these tiny air sacs would collapse when we breathe out if they didn t have surfactant—just like water bubbles collapse without dish soap. And every new breath would take a lot of force, like blowing up a new balloon. 

Oguchi, K., Ikegami, M., Jacobs, H., and Jobe, A. (1985). Clearance of large amounts of natural surfactants and liposomes of dipalmitoylphosphatidylcholine from the lungs of rabbits. Exp. Lung Res., 9, 221-235. 

Hydrophilic surfactant proteins A (SP-A) and D (SP-D), secreted by type II pneumocytes, interact specifically with a wide range of microorganisms and play important roles in the innate, natural defense system of the lung [16]. Both mRNA and protein levels of SP-A and SP-D increase dramatically in response to lung infection, injury and endotoxin challenge [17]. Type II pneumocytes also express class II major histocompatibility complex (MHC) antigens and intracellular adhesion molecule (ICAM-1), which may facilitate pulmonary immune responses [15]. 

There is nothing unnatural about surfactants. Sometimes when a man urinates into a toilet bowl he is surprised to see that it froths up as if his water contained a foaming agent. In fact it does, and it comes from his own urine discharging surplus natural surfactants. The human body produces these chemicals and they are particularly essential for the working of the lungs. 

LS (natural surfactant mixture from rat and rabbit lungs) 44 0.42... 

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