Christopher Marriott

Biopolymer Induced Changes in Mucus Viscoelasticity

The occurrence of macromolecules, other than glycoproteins, in the sputum of patients suffering from chronic obstructive airways disease is well documented (Ziment, 1978). The difficulties associated with the collection of ‘normal’ tracheobronchial mucus from healthy individuals renders it difficult to determine the effect that the contaminants which appear during disease exert. For example Creeth et al (1977) have demonstrated that it is impossible to remove free protein by isopynic ultracentrifugation in CsBr and a further separation in CsCl is necessary. This may suggest that a certain amount of free protein is associated with the glycoprotein even in the normal tracheobronchial tree. The transudation of serum proteins during infection together with the extracellular and breakdown products of bacteria are usually considered to be associated with an increase in the consistency of the sputum produced. However, conflicting reports have been published concerning the effect of DNA on the rheological properties of sputum (Puchelle et al, 1973; Bornstein et al, 1978). Therefore, it does appear important to establish the contribution of other constituents of sputum to the viscoelasticity; in this work we have used a mucus gel purified from human sputum for this purpose (Marriott et al, 1979).

The solubilization of progesterone by mixed bile, salt-phospholipid sols

The solubility of progesterone was determined in several different bile salt-phospholipid mixtures, and it is concluded that: (1) The solubility in unconjugated bile salts is greater than in the conjugated analogues, and the solubility in deoxycholate solutions is twice that in cholate solutions. (2) Substitution of hydroxyl groups in the 11 and 21 positions of progesterone increases solubility, whilst substitution in the 17-position decreases solubility in bile salt solutions. (3) Progesterone solubility in mixed bile salt solutions is proportional to the mole ratio of the surfactant mixture. (4) Sodium deoxycholate (SDC)-phospholipid sols show no such linear solubilizing properties; a minimum occurring at a mole ratio of SDC to phospholipid of 1 : 4. (5) There is a break in the solubility curve of progesterone in lysophosphatidycholine (LPC)/phosphatidylcholine (PC) mixtures at a mole ratio of 65 : 35 coincident with maximum viscosity. (6) Introduction of SDC into LPC/PC mixtures results in decreased progesterone solubility.

The effect of ageing on the rheological properties of gelatin gels

The effect of ageing at 4° on the viscoelastic properties of 1·5 and 2·0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1·5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution.

MODIFICATION OF THE RHEOLOGICAL PROPERTIES OF MUCUS BY DRUGS

The rheological properties of mucus secretions from various sites in the body are related to their particular physiological function. Although in normal circumstances the body produces secretions with optimal rheological properties to fulfil such functions, during disease the mucus produced may be too thick or too thin and in both cases may behave sub-optimally. In such situations it becomes attractive to administer chemical agents or drugs, either locally or systemically, which modify the rheological properties in an attempt to correct function. Furthermore, in certain cases it may be desirable to artificially manipulate the consistency of the mucus in order to produce a specific effect.

A Freezing Artefact Associated with the Preparation of Mucin for Examination Using the Scanning Electron Microscope

Scanning electron microscopy (SEM) of freeze-dried cervical mucus has been used to demonstrate that a filamentous or honeycomb structure exists (Chretien et al., 1973), with interconnecting channels separated by thin, membranous walls. This is interpreted as support for the channel theory of sperm migration (Odeblad, 1968). Forstner et al. (1977) have demonstrated a similar structure for intestinal goblet cell mucin. The purpose of the present study was to investigate the behaviour of human respiratory mucin in this respect, and to investigate parameters which might modify the observed appearance, with a view to understanding its biological significance.

Evaluation of Mucolytic Activity Using a Purified Mucus Glycoprotein Gel

The prime characteristic of chronic obstructive airways disease is hypersecretion of bronchial mucus which is invariably too thick to be cleared by the lung mucociliary system. In this situation the objective of therapy must be to reduce the visco-elastic properties of the abnormal secretion to the optimum value for removal by lung clearance mechanisms. The group of drugs which are designed for this purpose have been known as mucolytics and, while many compounds have been shown to be effect-ive in vitro, in clinical practice few can be considered successful (Ziment, 1978). Comparison of reported in vitro experiments is difficult because of the diversity and quality of the mucus systems used. The recent development of a model mucus preparation apparently consisting entirely of purified human bronchial mucus glycoproteins (Marriott et al, 1979) which are capable of gelation at low concentrations, should provide a suitable basis for the comparative evaluation of mucolytic agents.

Effect of S-carboxymethylcysteine on the biophysical and biochemical properties of mucus in chronic bronchitics.

The chemical heterogeneity of sputum has resulted in confusion about the effect of mucolytic agents used in the treatment of chronic obstructive airways disease. In disease states sputum is thought to become more viscous and this is associated with the production of a less acidic mucin with less hydrophilic groups, so that the macromolecules become more entangled, with more intermolecular bonding and decreased water retention (Havez et al, 1973). After treatment with S-carboxy-methy1cysteine (SCMC), some workers claim that the viscosity of sputum decreases, (Edwards et al, 1976), although increases have also been observed (Puchelle et al, 1978). It has been pointed out that elasticity and not viscosity may be the important factor controlling mucociliary transport (Richardson and Phipps, 1978; Medici and Radielovic, 1979).

A Rheological Study of Mucus - Antibiotic Interactions

Antibiotic therapy is commonly used both during acute exacerbations of bronchitis and prophylactically. Unless the antibiotic is instilled directly into the lung, then the transfer of the drug across the blood-bronchial barrier is a critical step. The maintenance of a homogeneous bactericidal or bacteriostatic concentration in the mucus is dependent upon the ability of the drug to diffuse through the mucus gel. The thickened hypersecretory mucus which is produced during infection may present a barrier to diffusion and this in turn may be affected by the antibiotic itself. Earlier work (Marriott and Kellaway, 1975) has indicated that tetracyclines exert a thickening effect on sputum. In this study we have examined the effect of a wide range of antibiotics on the rheological and mucociliary transport properties of a purified glycoprotein gel (Marriott et al, 1979).

The effect of blending on the rheological properties of gelatin solutions and gels

The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1·0–3·5% w/v at 25°), resulted in a decrease in gel rigidity whereas in the stronger gels (5–50% w/v at 25°) and solutions (18% and 30% w/v at 35°), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered.

The use of purified mucus glycoprotein gels in the assessment of mucolytic activity.

The effects of a wide range of mucolytic agents on the viscoelastic nature of a purified mucus glycoprotein gel have been investigated. The gel was produced by ultrafiltration of a solution containing high molecular weight glycoproteins obtained by gel chromatography in potassium thiocyanate. The fact that compounds as diverse as dithiothreitol and protease reduced the viscoelastic properties indicates that the model gel is appropriate for screening such compounds. Since it is homogenous and highly reproducible then it would appear to be ideal for such purposes. Also, it has been shown that mucus gels can be formed containing nothing but glycoproteins.