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Biomedical subjects

C Marriott

Publications and source records attributed to C Marriott.

At least 55 records · Page 3Linked to original sources
PubMed1992

The mitigating effects of phosphatidylcholines on bile salt- and lysophosphatidylcholine-induced membrane damage.

The effects, at pH 7.0, of a series of 0.2 mM phosphatidylcholines (PC), namely dicaproyl-PC (DCPC), didecanoyl-PC (DDPC), dilauroyl-PC (DLaPC), dimyristoyl-PC (DMPC), dipalmitoyl-PC (DPPC), dioleoyl-PC (DOPC) and dilinoleoyl-PC (DLPC) and a series of 0.2 mM fatty acid salts (namely sodium myristate, palmitate, stearate, oleate and linoleate) upon the erythrocyte haemolysis induced by 2 mM sodium taurodeoxycholate (STDC) were determined. The influence of egg PC and dihexadecyl phosphate (DHDP) concentration upon the haemolysis induced by 1.4 mM sodium deoxycholate (SDC), 2 mM STDC and 0.1 mM lysophosphatidylcholine (LPC) were also established. A bile salt:egg PC mole ratio of 0.5 virtually abolished the haemolysis induced by SDC and STDC, whereas the same ratio of LPC:egg PC only reduced haemolysis from 65 to 40% (maximum haemolysis). DHDP had no effect on the haemolytic action of SDC or STDC. The salts of the fatty acids were non-haemolytic, and when mixed with STDC did not affect the level of haemolysis induced by the bile salt. In contrast, DDPC and DLaPC enhanced the haemolysis of STDC and DCPC had no effect, whereas DMPC, DPPC, DSPC, DOPC, DLPC and egg PC all reduced haemolysis. Maximum reduction was determined for DMPC and egg PC. The mixed micelle preparation temperature (either room or 60 degrees C) and temperature of incubation (either 20 degrees C for 30 min or 37 degrees C for 5 min) had only minor effects on the net haemolysis induced by STDC. These findings may be of significance in understanding the aetiology of certain gastrointestinal diseases and in determining whether mixed bile salt micelles have a role as drug penetration enhancers.

Bile Acids and Salts↗
PubMed1991

The diffusion of beta-lactam antibiotics through mixed gels of cystic fibrosis-derived mucin and Pseudomonas aeruginosa alginate.

The rates of diffusion through purified extracellular alginate from Pseudomonas aeruginosa were measured for twelve beta-lactam antibiotics. The diffusion rate was reduced as the antibiotic molecular weight increased, but the range of diffusion rates exhibited by a common anti-pseudomonal penicillins was relatively small. The diffusion of ticarcillin through 1.0% w/v mixtures of alginate and purified mucus glycoprotein (mucin) from sputa of cystic fibrosis patients showed that, at equivalent concentrations, alginate represented the greater barrier to penetration. However if the mucin concentration was increased to 4.0% w/v, a more realistic physiological concentration, the diffusion of ticarcillin was retarded to a greater extent than in 1% w/v alginate, and the effect was compounded by other sputum components such as DNA. The results suggest that the antibiotic diffusion barrier represented by mucin may be significant in vitro, particularly for nebulized antibiotics.

Alginates↗
PubMed1991

The use of a radiolabelled saccharin solution to monitor the effect of the preservatives thiomersal, benzalkonium chloride and EDTA on human nasal clearance.

The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.

Adult↗
PubMed1991

Use of slime dispersants to promote antibiotic penetration through the extracellular polysaccharide of mucoid Pseudomonas aeruginosa.

Agents with the potential to reduce Pseudomonas aeruginosa alginate viscosity (slime dispersants) were shown to promote the diffusion of antipseudomonal antibiotics through alginate but were more effective in facilitating the diffusion of gentamicin than that of ceftazidime. EDTA increased the diffusion rates of these antibiotics by factors of 4.0 and 1.5, respectively, although sodium chloride significantly reduced viscosity and enhanced gentamicin diffusion.

Alginates↗
PubMed1990

Model systems for the evaluation of mucolytic drugs: acetylcysteine and S-carboxymethylcysteine.

The therapeutic place of mucolytic drugs remains uncertain; clinical studies have seldom demonstrated significant benefit and the activity of such agents is poorly understood. In this study the effects of the mucolytic agents acetylcysteine (AC) and S-carboxymethylcysteine (SCMC) have been assessed in-vitro, using purified mucus gels and tracheal explant systems and in-vivo, in the mini-pig tracheal pouch model, in order to elucidate their mechanisms of action. A reduction in the elastic modulus (up to 70% over the frequency range 0.2-20 Hz) was apparent after treatment of mucus gels in-vitro with AC (P less than 0.05), but not with SCMC. Gel chromatography indicated that AC reduced the mucus glycoprotein to smaller subunits and a breakdown of gel structure was apparent when visualized using a cryofracture technique. SCMC treated gels were comparable with control samples. Mucus production was assessed in isolated rat trachea by monitoring the uptake and release of [3H] glucosamine. AC (5-15 mM) did not affect secretion whereas SCMC (5 and 10 mM) reduced the production of radiolabelled material (24 and 37%, respectively) over 24 h (P less than 0.05). Single oral doses of SCMC and AC (20 mg kg-1) were administered to mini-pigs and mucus collected from tracheal pouches; no significant changes in the rheological or biochemical properties of the secretion could be determined. The in-vitro mucolytic activity of AC depends upon a direct action on the secretion, SCMC appears able to reduce production of the mucus glycoprotein. Wide inter- and intra-individual variation in the properties of the secretion would suggest that such effects are not readily demonstrated in-vivo.

Acetylcysteine↗
PubMed1990

The effect of some preservatives used in nasal preparations on the mucus and ciliary components of mucociliary clearance.

Efficient mucociliary clearance is a function of the physical properties of the mucus coupled to appropriately functioning cilia and may be altered by substances affecting ciliary beat frequency (CBF). Therefore the effect of preservatives on CBF was investigated using a photoelectronic technique. Methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, chlorbutol and chlorocresol inhibited beat frequency, an effect which was reversible upon rinsing out the first three compounds but not chlorocresol. The effect of chlorhexidine and phenylmercuric borate on CBF was complicated by an interaction with chloride ions in the media used. EDTA did not appear to be ciliotoxic, while the effect of benzalkonium chloride was variable. Thiomersal halted ciliary beating after 40-100 min. Mucociliary clearance may also be affected by an alteration of the physical properties of the mucus layer, therefore the effect of each compound on the rheological properties of purified pig gastric mucus glycoprotein was investigated. None of the preservatives significantly altered the viscoelastic properties of the gel, measured using dynamic techniques.

Animals↗
PubMed1990

The role of mucous glycoproteins in the rheologic properties of cystic fibrosis sputum.

Cystic fibrosis (CF) is characterized by excessive amounts of thick and tenacious mucous secretions that obstruct organ ducts and passages. In the respiratory tract this is associated with chronic infection resulting in the hypersecretion of purulent sputum, which the patient finds difficult to clear. We have studied the rheologic properties of purulent sputum from six patients with CF and five patients with chronic bronchitis to assess whether CF is associated with increased sputum viscoelasticity. In addition, we have isolated the major rheologic determinants, mucous glycoproteins, from CF and chronic bronchitis sputa and, using a magnetic microrheometer, investigated the possibility that the altered properties of mucus in CF are associated with abnormalities in these glycoproteins. Creep compliance analysis indicated that the CF sputa possessed raised levels of both elasticity (p less than 0.01) and viscosity (p less than 0.01). These increases in both rheologic parameters were found to be associated with increases in the DNA content (p less than 0.01) and dry weight (p less than 0.05). Mucous glycoproteins were isolated from CF and chronic bronchitis sputum samples by gel filtration on Sepharose CL4B, followed by concentration to form 8% wt/wt gels. In the absence of other sputum components, no abnormality in the rheologic properties of CF mucin gels could be detected. However, when DNA was added, the CF gels responded with increases in both elasticity and viscosity of as much as 30% (p less than 0.05), an effect not observed in the chronic bronchitis gels. These results suggest that a subtle abnormality may exist in CF mucous glycoproteins and that this could have a role in the altered physical properties of mucous secretions in CF.

Bronchitis↗
PubMed1990

The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum.

The relative importance of host and bacteria-derived deoxyribonucleic acid (DNA) in the increased viscoelasticity of purulent sputum in cystic fibrosis (CF) and other airway diseases is unclear. We report the identification of the DNA associated with mucus glycoproteins purified from the purulent sputum of 9 patients with CF. Mucus glycoproteins were purified from CF sputum by gel exclusion chromatography and the co-purifying DNA isolated by phenol extraction. Electrophoresis indicated that the DNA preparations had a size of approximately 300 to greater than 50,000 bases. The origin of the DNA was determined by slot blotting and subsequent hybridization with 32P-labelled DNA probes specific for human DNA sequences and those from bacterial species commonly isolated from CF sputum. The results indicated that in all cases the DNA was almost entirely human in origin. This implies that it is the patient's own DNA which may contribute to the rheological abnormalities of CF sputum.

Adolescent↗
PubMed1990

The effect of bromhexine hydrochloride on the viscoelastic properties of mucus from the mini-pig.

Mucus was collected daily from open-ended pouches established surgically in three mini-pigs. After a five day control period bromhexine hydrochloride (BHCl) was administered to each pig at dose levels of 0.5, 1.0 and 2.0 mg.kg-1 twice daily for five days. Each study period was followed by a five day washout period, when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. BHCl was shown to reduce the residual shear viscosity (p less than 0.05) and increase the instantaneous shear compliance at all dose levels (p less than 0.005), despite the large inherent intra- and inter-animal variation in the rheological properties of the daily samples. No change was found in the wet weight of the mucus samples throughout any of the study periods. This experimental model would appear to provide a valuable in vivo method of assessing the mucoregulatory potential of administered compounds.

Animals↗
PubMed1989

Hepatitis B screening in a northern Irish mental handicap institution: relevance to hepatitis B vaccination.

The current DHSS guidelines on immunisation against hepatitis B in mental handicap hospitals recommend vaccination for personnel at risk directly involved in patient care (who may have direct contact with patients or their body fluids) and for new admissions into institutions where the incidence is known to be high. We report a serological survey of hepatitis B markers in over 99% of the residents of a large mental handicap hospital. Of 720 patients tested only one carried hepatitis surface antigen. This patient was anti-HBe positive. Only 4.5% of the residents carried any hepatitis marker. These results do not suggest the need for a local vaccination programme for patients or staff.

Cross Infection↗
PubMed1989

The migration of bacteria through gels in the presence of IUCD monofilament tails.

An in vitro model was developed to investigate the migration of a variety of bacteria of different characteristics through a gel system in the presence or absence of a wide range of polymer monofilament threads. The bacteria were unable to migrate through the gel from the point of inoculation in the absence of a solid substrate. Migration occurred along all thread types tested, including those used as IUCD marker tails and the extent of bacterial migration appeared to be determined primarily by the motility of the microorganisms. The implications of these findings in relation to the development of pelvic infections in IUCD wearers is discussed.

Bacillus cereus↗
PubMed1989

The effect of some preservatives used in nasal preparations on mucociliary clearance.

The effect of methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, chlorbutol, chlorocresol, EDTA, benzalkonium chloride, chlorhexidine, phenylmercuric nitrate and phenylmercuric borate on mucociliary transport rate of the frog palate has been examined. Following a variable number of applications all these preservatives halted transport, the first three reversibly. However, applications of thiomersal (0.01%) were well tolerated. The frog palate possesses a ciliated epithelium protected by mucus, since some of our findings are at variance with those previously reported results where the protective effect of mucus was negligible in the in-vitro model (usually trachea) employed, it would appear that the contribution of mucus to effective mucociliary clearance should not be underestimated.

Administration, Intranasal↗
PubMed1989

Oral N-acetylcysteine or S-carboxymethylcysteine inhibit cigarette smoke-induced hypersecretion of mucus in rat larynx and trachea in situ.

Two weeks exposure of rats to cigarette smoke (CS) significantly (p less than 0.05) increased the secretion of fucose-containing glycoconjugates above normal in an in situ preparation of larynx and trachea. After equilibration mean basal secretion in CS-exposed rats was 24 micrograms (per 30 min collection) which was 8 times higher than that of unexposed animals (p less than 0.01). N-acetylcysteine (NAC) or S-carboxymethylcysteine (SCMC) given as 1% of the drinking water, before and after daily exposure to CS, significantly inhibited the development of the CS-induced increase in fucose secretion reducing the mean for basal secretion in each group to 7 and 5 micrograms, respectively (p less than 0.05). Neither NAC nor SCMC had significant effects on baseline glycoconjugate secretion in control animals. Albumin was inconsistently present in the secretions of both control and CS-exposed animals, whereas in those exposed to CS and also given one of the two cysteine derivatives there was a consistent increase in albumin transudation.

Acetylcysteine↗
PubMed1989

Drug-mucus actions and interactions.

Although it has generally been accepted that the main structural component of mucus secretions is the high molecular weight glycoprotein it has now been established that other macromolecules are co-secreted. For example, lysozyme, lactoferrin and albumin are known to be secreted by the serous cells within the sub-mucosal respiratory glands: significantly the albumin is synthesised within the cell and is not derived from serum. The various cells within the gland respond differently to agonists and since goblet cells, apart from when they are in the crypts within the gastro-intestinal tract, do not appear to be innervated, they cannot respond to any agonist as yet identified. It is therefore probable that the changes which occur during disease may result from changes in the sensitivity of a particular cell type to an agonist as this can markedly affect the type of secretion that is produced. Since the products of the serous cell form part of the natural defence system then the reduction in their number which is observed in chronic obstructive airways disease could also be significant in the disease process. Within the gastro-intestinal tract, it has now been established that substances which reduce the mucus structure can produce damage to the underlying membrane. The endogenous surfactants produced in bile are good examples and co-secretion of phosphatidylcholine provides a defence against self-digestion within the gut by the formation of mixed micelles. The importance of the mucus layer in the access of drug molecules to the absorbing epithelium has also been identified. The diffusion of water molecules is hindered even at concentrations below the gelling point (approximately 10-20 mg ml-1) and above this concentration a precipitate fall in diffusion coefficient is followed by a levelling off. This pattern is followed by low molecular weight drug molecules and a reasonable correlation between drug absorption and binding to mucus glycoproteins can be demonstrated. The agents which have been claimed to affect the quality and quantity of mucus secreted by the respiratory epithelium during conditions like chronic obstructive airways disease have been poorly understood. Recent studies have shown that compounds like bromhexine and S-carboxymethylcysteine can block the activity of mucus secretagogues in the rat. Furthermore, it has also been demonstrated that such compounds can prevent the inflammatory response to cigarette smoke. However, their activity is not restricted to the respiratory epithelium and the cervical mucus barrier has also been shown to be compromised following systemic administration.

Animals↗