ABSTRACT
Cystic fibrosis (CF) results from mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) which is a regulated chloride channel. The deltaF508 mutation prevents the post-translational glycosylation and membrane insertion of the protein. Severe disease follows, with the formation of a viscous mucus and subsequent chronic bacterial infection of the lungs, necessitating frequent, and often long, periods of antibiotic treatment. The pharmacokinetics of antibiotics in CF patients are abnormal, with lower blood serum levels and higher clearance rates which have never been satisfactorily explained. We found that accumulation of gentamicin in nasal polyp tissue non-CF cells was subject to regulation by the effectors and inhibitors of CFTR function; regulation was lost in deltaF508 CF cells and accumulation was more than doubled because of the inhibition of exocytosis.
Subject(s)
Cell Membrane/metabolism , Cystic Fibrosis/metabolism , Gentamicins/pharmacokinetics , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , 1-Methyl-3-isobutylxanthine/pharmacology , Adenosine Triphosphate/metabolism , Adenylyl Imidodiphosphate/pharmacology , Adult , Cell Membrane/drug effects , Child , Child, Preschool , Colforsin/pharmacology , Cyclic AMP/analogs & derivatives , Cyclic AMP/pharmacology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Energy Metabolism , Female , Fluorescein-5-isothiocyanate/pharmacokinetics , Gentamicins/metabolism , Humans , Male , Middle Aged , Nasal Polyps , Thionucleotides/pharmacologyABSTRACT
Chlorhexidine did not inhibit ATPase in intact cells of Escherichia coli K12 W1317i-, even at bactericidal concentrations, and ATP hydrolysis was greatest at the highest concentration (40 mg/l), even though no net uptake of substrate occurred. Like dinitrophenol and tribrominated salicylanilide, polymyxin and chlorhexidine collapsed the membrane potential at inhibitory concentrations. Membrane disruption, and not ATPase inactivation, is considered the lethal event in chlorhexidine action.
Subject(s)
Chlorhexidine/pharmacology , Escherichia coli/drug effects , Adenosine Triphosphate/metabolism , Biological Transport, Active/drug effects , Cell Membrane Permeability/drug effects , Escherichia coli/metabolism , Membrane Potentials/drug effects , Methylgalactosides/pharmacokinetics , Protons , Thiogalactosides/pharmacokineticsABSTRACT
A correlation between the multiple drug resistance patterns and the plasmid profiles given by 70 clinical isolates of Shigella sonnei and Shigella flexneri was investigated in this study. The most common plasmids were purified from different isolates by electroelution and characterized via restriction endonuclease digestions.
Subject(s)
Anti-Bacterial Agents/pharmacology , DNA, Bacterial/analysis , R Factors , Shigella flexneri/drug effects , Shigella sonnei/drug effects , Drug Resistance, Microbial/genetics , Humans , Restriction Mapping , Shigella flexneri/genetics , Shigella sonnei/geneticsABSTRACT
The Rappaport-Vassiliadis (RV, modification of Rappaport's) medium was superior to Muller-Kauffmann tetrathionate broth (MKT) for the enrichment and isolation of salmonellas from sewage sludge samples, either naturally contaminated or artificially inoculated with salmonella. Isolation rates for RV (42 degrees C) were higher even when MKT (43 degrees C) performance was improved by the use of brilliant green sul-phamandelate agar. Kinetic results show that the suppression of the competing flora was poorer in MKT than in RV. The use of high inoculum to medium volume ratios (e.g. 1:5000) increased the isolation rates from RV and kinetic data explain why this was so.
Subject(s)
Culture Media , Salmonella/isolation & purification , Sewage , Salmonella/growth & developmentABSTRACT
A technique for investigating the kinetics of salmonella enrichment is reported. Its use with four enrichment media (Rappaport's medium, Muller-Kauffmann tetrathionate broth (MKT) tetrathionate broth and selenite F) is described and the effect of elevated temperature on the growth kinetics shown. Rappaport's medium at 37 degrees C and MKT at either 37 degrees C or 42 degrees C were far superior to selenite F and tetrathionate broth in their selective properties and, with the exception of Rappaport's medium, the use of elevated temperature increased the selectivity of the media.
Subject(s)
Culture Media , Salmonella typhimurium/growth & development , Salmonella/growth & development , Escherichia coli/growth & development , Kinetics , Proteus vulgaris/growth & development , Pseudomonas aeruginosa/growth & development , Salmonella/isolation & purification , Salmonella typhimurium/isolation & purification , Selenium/pharmacology , Temperature , Tetrathionic Acid/pharmacologyABSTRACT
Direct microscopical observations of single developing cysts in sealed slide microcultures prepared from 5-days-old tube cultures of the Reiter treponeme revealed two distinct phases in the life cycle. In one phase transverse fission was the main method of multiplication while in a second phase, occurring when conditions in the medium became unfavourable for propagation, cysts developed. These could release large numbers of actively motile treponemes when returned to optimum growth conditions. These observations, together with results of the dilution method for the calculation of the Most Probable Number and the absence of a response in treponemes killed by high temperature (45 degrees C) or abnormal pH (10), showed that the cysts were viable and a mode of propagation for the Reiter treponeme.
Subject(s)
Treponema/growth & development , Anaerobiosis , Animals , Bacteriological Techniques , Reproduction, Asexual , Treponema/physiologySubject(s)
Chlorhexidine/pharmacology , Colistin/pharmacology , Polymyxin B/pharmacology , Polymyxins/pharmacology , Pseudomonas aeruginosa/drug effects , Bacterial Proteins/metabolism , Drug Synergism , Membrane Proteins/metabolism , Phospholipids/metabolism , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/metabolismABSTRACT
Five different types of surgical mask of varying design and composition of natural and synthetic fibres were tested for their efficiency in vivo by means of a special test chamber. Contaminated particles escaping through or around the mask during speech by the wearer could be collected and sized. Analysis of the data showed that the gross efficiency of all the masks was high, but that some masks were distinctly better at small particle 'filtration' than others. There was a significant difference in efficiency between the best and worst masks. The best masks contained more fabric, were softer and were pleated, while the worst were stiffer, smaller and not pleated. Reusable cotton fabric masks were as effective as synthetic fabric masks when made to a good design.
