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Biomedical subjects

C Marriott

Publications and source records attributed to C Marriott.

At least 73 records · Page 4Linked to original sources

Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa.

The interaction of five anti-pseudomonas antibiotics with both commercial and pseudomonas alginates was studied by investigation of their binding and diffusion characteristics. The two sources of alginate were qualitatively but not quantitatively similar in these respects. Unlike the beta-lactams, gentamicin and tobramycin bound avidly to both sources of alginate and, when the alginate gel to antibiotic ratio was high, the aminoglycosides exhibited diffusion coefficients which were approximately 20% of the beta-lactam values. At much lower ratios of alginate to antibiotic the aminoglycosides caused precipitation in the alginate with apparent disruption of the gel structure, and ultimately penetrated the gel at a faster rate than the beta-lactams. The strong aminoglycoside binding to alginate was reduced, but not eliminated by the presence of physiological concentrations of salts.

Alginates↗

Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay.

A non-occluded multiple application skin blanching assay has been used to determine the effect of applied phosphatidylcholine (PC) on the bioavailability of corticosteroids. One forearm of each of ten volunteers was treated twice daily for one week with PC presented as a liposomal suspension in Sørensen's (pH 5.0) phosphate buffer (2.5 mg PC/0.5 mL) while the other arm was treated with 0.5 mL of phosphate buffer. For the following two weeks this treatment regimen was continued but in addition, each of four corticosteroid formulations (containing (i) hydrocortisone 0.1%, (ii) clobetasone butyrate 0.05%, (iii) betamethasone 0.1% and (iv) clobetasol propionate, 0.05%) was applied to sites on both arms. 5 +/- 1 mg of each cream was applied twice daily to the sites on day 1, then once daily for a further four days; after two days of no application, the protocol was repeated. Estimation of pallor was usually made four times daily. At the end of the second week of corticosteroid application the blanching response to all four formulations on the PC treated arms was significantly higher than on the buffer treated arm. Tachyphylaxis to the applied corticosteroids was markedly less apparent on the lipid-treated arms. It is proposed that the applied phospholipid either supplements the lipid content of the skin or provides a thin film in intimate epidermal contact. Such a film may promote hydration of the stratum corneum and also provide an environment into which corticosteroids initially partition before a subsequent, more controlled, release to the underlying tissue.

Administration, Topical↗

Binding and diffusion characteristics of 14C EDTA and 99mTc DTPA in respiratory tract mucus glycoprotein from patients with chronic bronchitis.

Measurement of pulmonary clearance of an inhaled aerosol of technetium-99m labelled diethylenetriaminepenta-acetate (DTPA) by external detection methods has been used widely as an index of permeability across alveolar epithelium and bronchial mucosa. To determine the applicability of the tracer to measurement of permeability in the airways the diffusion and binding characteristics of 99mTc DTPA and the chemically related ethylenediaminetetra-acetic acid labelled with carbon-14 (14C EDTA) was studied in purified respiratory tract mucus glycoprotein from patients with chronic bronchitis. The diffusion coefficients for 99mTc DTPA and 14C EDTA through mucus gels were significantly lower than those for tritiated water. Both molecules bound to the mucus gels with high affinity at two independent low capacity sites. Appreciable amounts of 99mTc DTPA or 14C EDTA are therefore unlikely to cross mucus layers of physiological thickness over periods of four or five hours. This suggests that when pulmonary clearance is determined by the 99mTc DTPA method the tracer retained in mucus lined airways will provide background activity. This study supports the assumption that pulmonary clearance measurements are mainly measuring alveolar epithelial permeability and should not be used to study bronchial epithelial permeability.

Bronchitis↗

Cigarette smoke-induced 'chronic bronchitis': a study in situ of laryngo-tracheal hypersecretion in the rat.

Mucous secretion and mucosal permeability by the larynx and trachea, isolated in situ, was investigated in normal rats and in those in which 'chronic bronchitis' was induced by daily exposure to cigarette smoke for 2 weeks. Fucose was used as a specific marker for the secretion of mucus glycoprotein, and hexose and protein were markers both for mucus and plasma-type glycoproteins present in tissue fluid transudate. Albumin was used as an indicator of the contribution of serum to the secretions. After equilibration, the mean basal secretion of fucose (microgram/30 min collection) was significantly higher in 'bronchitic' rats than in the controls (P less than 0.01). Mean values for controls were: fucose 3 (SEM 1: n = 9), hexose 41 (SEM 9; n = 8), protein 1082 (SEM 385; n = 8), albumin less than 2 (n = 8); for 'bronchitic' rats the values were: 24 (SEM 6; n = 7), 101 (SEM 26; n = 8), 2000 (SEM 520; n = 8) and less than 2 micrograms (n = 7) respectively. In control and bronchitic animals acute administrations of cigarette smoke, blown directly through the laryngo-tracheal segment after equilibration, caused significant (P less than 0.05) transient increases in the secretion of fucose, hexose and protein, but not of albumin.

Animals↗

The effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on guinea-pig uterine microflora.

This study used guinea-pigs as a mammalian model to investigate the effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on the integrity of the cervical mucus plug. It was shown that under normal circumstances the uterus is sterile, but following drug administration microorganisms began to appear in the uterus with no significant effect on the vaginal microbial population. It therefore appears that these two mucolytic agents may reduce cervical mucus viscoelasticity. After the animals had been mated, microorganisms were isolated from the uterus even in the absence of drug treatment.

Animals↗

Upper respiratory tract secretions: pathophysiology.

Nasal fluid is a heterogeneous substance. It consists largely of a secretory product derived from the 100,000 small seromucous glands. The anterior part of the nose has a relatively high secretory capacity, but this does not seem to be caused by secretion from the 200 anterior serous glands. Compared to sputum, nasal secretion has a lower viscosity, but comparable spinability; it has a lower dry weight, and content of sulphate, sugars and most proteins, but a comparable level of albumin. Watery rhinorrhoea is mainly reflex-mediated. Watery, but not purulent nasal discharge can be reduced by the cholinoceptor antagonist, ipratropium, administered in a dose which matches the degree of the symptoms. It seems likely that the nose, in some respects, can serve as a model for the analysis of airway secretions, but a comparative study of nasal and of bronchial secretions sampled in an identical way is warranted.

Allergens↗

Biochemical analysis of nasal secretions induced by methacholine, histamine, and allergen provocations.

Nasal provocation tests with methacholine, histamine, and allergen were performed outside the pollen season in 26 pollen-allergic subjects with the aim of sampling nasal secretions for biochemical characterization. Sugar analyses showed that methacholine-induced secretions were a mixture of serous and mucous glycoproteins. Compared with published sputum values, the levels of proteins and sugars were approximately 5 times lower in the methacholine-induced secretions (protein, 6 mg/ml; hexose, 2 mg/ml), whereas the albumin concentrations were comparable (1 mg/ml). Histamine-induced secretions as well contained a mixture of serous and mucous glycoproteins and a high albumin level (3 mg/ml), indicating a relatively higher degree of transudation than in methacholine- and allergen-induced secretions. Allergen-induced secretions had a low dry weight (mean, 19 mg/g; p less than 0.05) and protein (mean, 4 mg/ml; p less than 0.01) content compared with that in methacholine- and histamine-induced secretions; they contained mainly mucous glycoprotein, and the albumin level was relatively low. Thus, nasal secretions have lower dry weight, sugar and protein content than does sputum; histamine provokes marked transudation; methacholine and allergen do not; methacholine and histamine produce a mixture of serous and mucous glycoproteins; allergen produces mainly mucous glycoproteins.

Adolescent↗

The influence of native porcine gastric mucus gel on hydrogen ion diffusion: the effect of potentially ulcerogenic agents.

Experiments were carried out to investigate the ability of native gastric mucus gels to retard hydrogen ion diffusion. Mucus held between two polycarbonate membrane filters in a diffusion cell, separating equimolar solutions of NaCl and HCl, significantly reduced the rate of hydrogen ion diffusion and increased the time for the mean hydrogen ion front to traverse the mucus compartment (lag time) when compared to an unstirred layer of saline (P less than 0.01). N-acetylcysteine, sodium taurodeoxycholate and acetylsalicylic acid significantly increased the diffusion rate (P less than 0.025); the lag time was significantly reduced by N-acetylcysteine (P less than 0.001). In addition mucus gels were found to have buffering capacity at a pH greater than 2. These observations suggest that native gastric mucus gels can retard hydrogen ion diffusion and that this retardation of diffusion is reduced by agents which are potentially damaging to the gastric mucosa.

Animals↗

A new mucotropic agent--in vitro and in vivo evaluation of 2-alpha-thenoylthiopropionylglycine (bronchoplus).

A new mucotropic agent, 2-alpha-thenoylthiopropionylglycine (TTPG) has been evaluated using two in vitro mucus models (pig gastric mucin and human bronchial mucus) and an in vivo model, the oral administration for a period of 7 days to a mini-pig fitted with a tracheal-pouch. TTPG at 2% concentration caused a 40% reduction in the viscosity of mucus gels in vitro, as compared to a control with water. Tracheal mucus samples collected from the pouch were examined rheologically and biochemically. The amount of glycoprotein secreted increased after administration of TTPG (440 to 616 micrograms/mg dry weight). The glycoproteins also appeared to be more acidic after TTPG. An increase in the sulphydryl concentration of the mucus was observed, suggesting that a hydrolysis product of TTPG had crossed the blood-mucus barrier. An increase in the viscosity and elasticity of the mucus gel occurred during the treatment period.

Acetylcysteine↗

Counter-ion binding to mucus glycoproteins.

The affinity of pig gastric mucus glycoprotein for counter ions of various valencies was examined. Ions of higher valency were bound with increasing avidity, but the degree of binding was apparently not influenced by the ionic radius. The affinity of the glycoprotein for the ions studied may be ranked: Fe3+ greater than Al3+ greater than Ca2+ greater than Cs+ congruent to Na+. The binding of calcium was inhibited by high ionic strength and was sensitive to the pH of the environment. Enzymatic removal of sialic acid slightly reduced the calcium binding capacity.

Animals↗

Cation induced changes in the rheological properties of purified mucus glycoprotein gels.

The effects of mono-, di- and trivalent ions on the rheological properties of a purified mucus glycoprotein gel have been investigated. Monovalent ions increased the fluidity of the gels in a concentration dependent manner. The effect of calcium was pH dependent; at neutral pH values this ion produced a maximum in the gel viscoelasticity at a concentration of 0.5 mM, whilst at pH 5.0 the increase in viscoelasticity was sustained up to 3.0 mM. The same concentrations of copper (II) at pH 5.0 had a similar but greater effect on the viscoelasticity. Al3+ at pH 3.0 increased the viscoelastic moduli throughout the range studied (0.1-2.0 mM), whereas iron made the gels more fluid at low concentrations, but increased the viscoelasticity to above control values at a concentration of 2.0 mM.

Animals↗

Selected methods for the evaluation of the effects of drugs on mucus viscoelasticity and mucociliary clearance.

In order to rationally test the efficacy of mucolytic and mucospissic compounds, their effects upon mucus viscoelasticity, ciliary beat frequency (c.b.f.) and total mucociliary transport rate (t.t.r.) must all be determined. Methods are described which allow the measurement of the viscoelastic modulii of small (10 microL) quantities of mucus, while c.b.f. and t.t.r. are determined using the frog palate model.

Animals↗

The effect of flavour on acceptability of antacid tablets.

One hundred healthy volunteers recorded their subjective impressions of taste, mouth feel, after-taste and preference, after receiving in turn two tablets of each of four commonly-used antacids. The subjects remained unaware of the appearance of name of the products. The orange flavoured tablets, Asilone Orange, were shown to have a more acceptable taste, mouth feel and after-taste than three other commonly used antacids, Gaviscon, Altacite Plus, and Aluminium Hydroxide B.P., and these differences were highly significant (P less than 0.0001). Furthermore, 93% of cases expressed a willingness to take the orange flavoured tablets again, on a long term basis if necessary.

Adult↗

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.

Compliance↗