Lung surfactant syndrome

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... 

For the treatment of lung surfactant deficiency in premature human infants suffering from respiratory distress syndrome, limited clinical trials were performed showing that liposomes in the lung-instilled intratracheally either as an aerosolized mist (Ivey et al., 1977) or as a suspension via an endotracheal tube (Fujiwara et al., 1980)—rapidly improved lung function. No adverse effects were observed as a result of the supplementation with surfactant-like material. It appears, therefore, that liposomes are a suitable system for the delivery of major phospholipid components of endogenous lung surfactant. 

Deficiency of Lung Surfactant Causes Respiratory Distress Syndrome... 

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. 

Phospholipids and sphingolipids are involved in several disease processes, including respiratory distress syndrome (lack of lung surfactant), multiple sclerosis... 

Conversely, the role of perfluorocarbons for oxygen transport and in vivo delivery is investigated. In addition to possible use as temporary blood substitute, these fluorocarbon molecules can be applied as respiratory gas carriers, for instance as lung surfactant replacement compositions for neonates and possibly for the treatment of acute respiratory distress syndrome for adults. Another... 

Phospholipid that is the major component of Tung surfactant, and the syndrome caused by its deficiency Dipalmitoylphosphatidylcholine (DPPC, also called dipalmitoyllecithin, DPPL) is the major lipid component of lung surfactant. It is made and secreted by type II granular pneu-mocytes. Insufficient surfactant production causes respiratory distress syndrome, which can occur in preterm infants or adults whose surfactant-producing pneumocytes have been damaged or destroyed. 

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. 

Dipalmitoyl phosphatidyl choline is one component of human lung surfactant, which coats the inner surfaces of the lung membranes and prevents them from clinging together and collapsing. Premature infants often produce little or no lung surfactant, which can lead to collapsed alveoli and other symptoms of infant respiratory distress syndrome (IRDS). 

Dipalmitoylphosphatidylcholine serves as the lung surfactant in adults, allowing the lungs to function normally. This phospholipid develops in the fetus after week 30 of gestation. Premature infants do not have an adequate amount of this phospholipid. As a result, acute respiratory distress syndrome is a leading cause of morbidity and death in premature infants. 

D. Respiratory distress syndrome is caused by a deficiency of lung surfactant, which is composed mainly of dipalmitoylphosphatidylcholine. 

Mustard gas exposure also causes inflammatory lung diseases, including acute respiratory distress syndrome (ARDS) (Calvet et al., 1994 Sohrabpour, 1984). A defective secretion of surfactant by alveolar type 11 cells has been implicated as one of the causative factors for the development of ARDS (Ansceschi, 1989). A major component of lung surfactant is DPPC (Stith and Das, 1982). The precursor of DPPC is normally l-pahnitoyl-2-oleolyl PC. DPPC is produced by deacylation and subsequent reacylation with palmitic acid at 2-position of glycerol moiety of the unsaturated phospholipid. 

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. 

The respiratory distress syndrome (RDS) of a premature infant such as Colleen Lakker is, in part, related to a deficiency in the synthesis of a substance known as lung surfactant. The major constituents of surfactant are dipalmitoylphosphatidyl-choline, phosphatidylglycerol, apoproteins (surfactant proteins Sp-A,B,C), and cholesterol. 

Chrysotile, as well as chrysotile after SO2 sorption, instilled via the rabbits trachea induced an increase in the unsaturated fatty acid content of lung surfactant, which was similar to that observed in the respiratory distress syndrome of the new-born, and an increase in the protein level of pulmonary washings which may be explained by an increase of the permeability of the blood-air barrier (Oblin et al. 1978). 

Depletion forces can be of use in biomedical applications. Non-adsorbing polymer chains promote the adhesion of cells to surfaces [256] and enhance adsorption of lung surfactants at the air/water interface in lungs so as to help patients suffering from acute respiratory syndrome [257]. The physical properties of actin networks are affected by non-adsorbing polymers [258], which also modify phase transitions in vims dispersions [228]. 

Phospholipids play an important role in lung functions. The surface active material to be found in the alveolar lining of the lung is a mixture of phospholipids, neutral lipids and proteins. Lowering of surface tension by the lung surfactant system and the surface elasticity of the surface layers assists alveolar expansion and contraction. Deficiency of lung surfactants in newborns leads to a respiratory distress syndrome and this led to the suggestion that instillation of phospholipid surfactants could cure the problem. 

A common problem for premature babies is their lack of pulmonary surfactant. The pulmonary surfactant is formed late in pregnancy, and a premature baby born without the surfactant can experience respiratory distress syndrome, whereby the alveoli can collapse, a potentially fatal condition. Treatment of newborn premature babies with a lung surfactant therapy was a major advance in neonatal medicine. 

A liposomal formulation containing a surfactant, which usually coats the mucosa of the bronehi and prevents a collapse of the alveolar vesieles of the lung, has been developed for patients who suffer from infant respiratory distress syndrome (IRDS) or adult-aequired respiratory distress syndrome (ARDS). Premature babies often suffer IRDS before the development of a funetional lung surfaetant and pulmonary gas exehange. ARDS is also a life-threatening failure and loss of the lung function and is usually acquired by illness or accident. Clinieal trials with liposomal surfactant have proved to be effective in prophylaetie treatment of IRDS and ARDS. 

When air is exhaled the small alveoli of the lungs could collapse if it were not for the surface active material (surfactant) present in the fluid that coats the lungs. e In fact, the lack of adequate surfactant is the cause of respiratory distress syndrome, a major cause of death among premature infants and a disease that may develop in acute form in adults. The surfactant material forms a thin film of high fluidity at the air-liquid interface and lowers the surface tension from the 72 mN/m of pure water to <10 mN/mfs (Pay attention to the definition of surface tension.11)... 

Alveoli represent the primary site for gas exchange within the lung, and thus their health is vital for survival. Alveolar conditions with a primary genetic cause, such as surfactant protein-B (SP-B) deficiency and SP-C deficiency, are prime candidates for a rAAV-gene therapy approach. Diseases in which alveoli are damaged secondary to other defects might also be treated with gene transfer. Such conditions include environmental toxin exposure, infectious diseases, and adult respiratory distress syndrome (ARDS) (Table 4.1) (Rolls et al., 1997, 1998, 2001 Cheers et al 1999 Ruan et al., 2002). 

In adults, a severe form of lung injury can develop in association with sepsis, pneumonia, and injury to the lungs due to trauma or surgery. This catastrophic disorder is known as acute respiratory distress syndrome (ARDS) and has a mortality rate of more than 40%. In ARDS, one of the major problems is a massive influx of activated neurophils which damage both vascular endothelium and alveolar epithelium and result in massive pulmonary edema and impairment of surfactant function. Neutrophil proteinases (e.g., elastase) break down surfactant proteins. A potential therapeutic strategy in ARDS involves administration of both surfactant and antiproteinases (e.g., recombinant a I -antitrypsin). 

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